Collagen banking is a proactive skincare strategy falling under the category prejuvenation aimed at preserving and stimulating collagen production to maintain youthful, firm and excellent skin quality over time. This approach can involve using various treatments, tweakments, products, supplements and lifestyle choices to boost collagen levels before significant signs of aging appear. The goal is to build a "reserve" or “bank” of collagen, ensuring skin remains resilient and less prone to wrinkles and sagging as natural collagen production declines and degradation increases with age. To start banking collagen as early as in your twenties makes sense, as the producing cell called the dermal fibroblast is still very healthy and active. Moreover as the loss is not yet so great (just a few percent loss), thus less invasive methods work well to maintain a youthful status quo. I´s never too late to start “banking” collagen, although when you are more mature, the word rejuvenation might be more suitable. 
 
There is no direct scientific evidence that collagen stimulation is more effective in your twenties than in your sixties.
However, starting collagen stimulation earlier may be beneficial:
▌Collagen production begins to decline around age 25-30, decreasing by about 1% per year.
▌By the 50s and beyond, the collagen loss is greater >30%, becomes more noticeable and it´s always harder to get back what you lost than to maintain what you have.
▌Peak collagen levels occur at twenty years of age, thus maintaining what you have the highest achievable level.
▌Starting collagen stimulation treatments earlier may help prevent further collagen loss and require less invasive and number of treatments.
 
WHAT IS COLLAGEN
Collagen is the most abundant protein in the human body, making up about one-third of all proteins. 
1. Location: Found in connective tissues, including skin, tendons, bones, and cartilage.
2. Function: Provides structural support, strength, and elasticity to tissues.
3. Production: Naturally produced by the body, but production decreases with age, starting around the mid-20s.
Collagen plays a crucial role in maintaining skin elasticity, joint health, and overall tissue integrity. As collagen production declines with age, so does the skin quality, leading to visible signs of aging like wrinkles, loss of elasticity and firmness, and sagging skin. Collagen is one of the key target components for noticeable and effective skin rejuvenation or regeneration. 

Collagen is primarily composed of three key amino acids: 
▌Glycine: is the most abundant, contributing significantly to collagen's structure and stability 
▌ Proline
▌ Hydroxyproline
Proline and hydroxyproline are crucial for forming the triple-helix structure of collagen, which provides strength and flexibility. Additionally, essential amino acids like lysine play a critical role in collagen synthesis by forming hydroxylysine, important for stabilizing collagen fibers. A balanced intake of these amino acids is vital for maintaining healthy collagen levels in the body.

COLLAGEN DECLINE
Collagen production begins to diminish naturally in our mid-20s, decreasing by about 1% per year [2]. This decline becomes more pronounced in the 40s and 50s, contributing to visible signs of aging such as wrinkles and sagging skin [2]. Factors influencing collagen loss include genetic predisposition (DNA), changes in epigenetic pattern (influenced by environment), hormonal changes (especially post-menopause), and fibroblast aging [2][3].

1. Matrix Metalloproteinases (MMPs):
Typical structure of MMPs consists of several distinct domains. MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs [6].
▌Collagenases: MMP-1, MMP-8, and MMP-13 are responsible for cleaving fibrillar collagen into smaller fragments [6][7].
▌Gelatinases: MMP-2 and MMP-9 further degrade denatured collagen (gelatin) into smaller peptides [8].
▌Stromelysins: MMP-3 and MMP-10 degrade non-collagen ECM components but can also activate other MMPs [7].
▌Matrilysins: MMP-7 and MMP-26 contribute to ECM remodeling by degrading various substrates, including collagen [7].

​2. Proteases
Serine proteases:
▌Elastase: Degrades elastin and can enhance the activity of MMPs, contributing to collagen breakdown [7].
Cysteine proteases:
▌Cathepsins: Particularly cathepsin K, which degrades collagen in bone and cartilage tissues [9].
Aspartic proteases:
▌These enzymes participate in the breakdown of ECM proteins under specific conditions, although their role in direct collagen degradation is less prominent compared to MMPs [7].
Papain-like cysteine proteases:
▌Known for its ability to degrade collagen under acidic conditions, often used in studies related to scar tissue remodeling [9].
 
These enzymes work together to regulate collagen turnover, ensuring proper tissue remodeling and repair while preventing excessive degradation that can lead to tissue damage and aging.

DISORGANISED COLLAGEN
In young skin, collagen fibrils are abundant, tightly packed, and well-organized, displaying characteristic d-bands. 
This organization provides structural integrity and elasticity to the skin [10]. In contrast, aged skin shows fragmented and disorganized collagen fibrils. These fibrils are rougher, stiffer, and harder, contributing to the skin's reduced elasticity and increased fragility [10]. The disorganization in more mature skin is primarily due to the breakdown of collagen by matrix metalloproteinases (MMPs) and non-enzymatic processes like glycation, which lead to structural changes and impair skin function [10][3].

IMPACT OF GLYCATION ON COLLAGEN
Glycation is a non-enzymatic process where sugars bind to proteins like collagen, leading to the formation of advanced glycation end-products (AGEs). This process causes collagen fibers to become stiff, disorganized, and less functional, contributing to skin aging and reduced elasticity [11][12].
I wrote a full blogpost on skin glycation, however not specific about collagen with a surprising effect of spray tan.  Read more.
 
Prevention and treatment of glycation [13][14][15]
1. Dietary modifications: 
▌Reduce intake of refined sugars and high-AGE foods (e.g., fried and processed foods).
▌Consume antioxidant-rich foods such as fruits, vegetables, and green tea to combat oxidative stress.
2. Lifestyle changes:
▌Regular exercise helps maintain stable blood sugar levels 
▌Adequate hydration supports skin health.
3. Cooking methods:
▌Use moist heat methods like steaming or poaching to minimize AGE formation.
4. Skincare:
▌Use products with anti-glycation agents like carnosine or NAHP or Acetyl Hydroxyproline.
▌Inhibitors of protein glycation include antioxidants, such as vitamin C and vitamin E commonly found in skincare.

​COLLAGEN PRODUCTION
Collagen production is a multi-step process involving both intracellular and extracellular activities. 

1. It begins with the synthesis of procollagen in fibroblasts, where genes are transcribed into mRNA, which is then translated into polypeptide chains in the rough endoplasmic reticulum RER. 
2. These chains undergo hydroxylation of proline and lysine, a process dependent on vitamin C, and glycosylation [16]. 
3. The chains form a triple helix structure called procollagen, which is transported to the Golgi apparatus for further modifications before being secreted outside the cell.
4. Once outside, enzymes cleave procollagen to form tropocollagen, which assembles into collagen fibrils through covalent cross-linking facilitated by lysyl oxidase. 
5. These fibrils aggregate to form collagen fibers, providing structural integrity to tissues like skin, bones, and tendons [16]. 

SKINCARE INGREDIENTS THAT STIMULATE COLLAGEN PRODUCTION
 
1. Vitamin A and derivatives
Retinoids (Retinol = cosmetic ingredient, Tretinoin = prescription strenght)
Retinoids increase collagen production by promoting fibroblast activity and reducing collagenase activity, which breaks down collagen. This is a dose-dependant effect. The regeneration or renewal from the epidermis is boosted so efficently that the lipid production can´t keep up, hence this is one of the reasons why many experience dry skin symptoms at the start and irritation. Lipids are like the morter between the bricks of the skin barrier. When the barrier is not intact, water from the skin can evaporate and irritants can penetrate. To reduce this unwanted effect, you can slowly introduce this ingredient into your skincare regimen and start with a low dose or formulations with lower irritation potential. Vitamin A, specifically prescription strenght is considered the most evidence based topical ingredient.
 
2. Vitamin C (Ascorbic Acid)
Vitamin C, also known as ascorbic acid, plays a crucial role in collagen synthesis and maintenance, significantly influencing skin health and structural integrity. Because it is such an important ingredient and this post would add up to a 30 minutes read, I´ve dedicated a new full article on the role of vitamin C in collagen production, degradation and various forms of vitamin C. Click here.

3. Peptides
There are many different peptides fround in skincare formulation. We can identify the following main types by function:
1. Carrier peptides: These help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes.
2. Signal peptides: These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells.
3. Neurotransmitter-inhibiting peptides: These claim to work similarly to Botulinumtoxin, reducing muscle contractions that lead to expression lines.
4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins.
5. Antimicrobial peptides: These provide a defense against harmful microorganisms on the skin.
6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage.
 
Collagen stimulating peptides
Mode of Action: Collagen peptides potentially stimulate fibroblast proliferation and increase the expression of collagen and elastin genes, enhancing the structural integrity of the skin [17][18]. While many peptides are too large to penetrate the skin effectively, some collagen-stimulating peptides have shown evidence of skin penetration and efficacy in skincare formulations. 

1. Penetration-enhancing techniques: Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers [19].

​2. Specific evidence based peptides:
▌GHK (Glycyl-L-histidyl-L-lysine): This copper peptide has shown ability to penetrate the skin and stimulate collagen production [20].
▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects [20].
▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems [21]. GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts [22]. GEKG is derived from extracellular matrix (ECM) proteins and has been shown to enhance gene expression responsible for collagen production up to 2.5-fold, boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts [22].
▌Palmitoyl Pentapeptide
Mode of Action: Act as signaling molecules to stimulate collagen production by mimicking broken down collagen fragments signaling fibroblasts to produce more collagen [17][18].
 
Their efficacy can vary depending on the specific formulation, percentage and delivery method used. More about peptides click here

​4. Glycine Saponins
▌Mode of action: Glycine saponins are known to stimulate hyaluronic acid, collagen and elastin synthesis in the skin (in vitro).
 
5. Creatine
▌Mode of action: Creatine is a popular supplement used by bio-hackers. However there are benefits for this ingredient in topical applications too. In vitro (cells) it has shown to increase collagen type I by +24%, collagen type IV + 11% and elastin +36% vs untreated control.
 
7. Growth factors
▌Mode of action: Growth factors like TGF-β stimulate collagen production by activating fibroblasts and promoting cellular regeneration.TGF-β has been shown to enhance the production of types I and III collagens by cultured normal human dermal fibroblasts, with a 2-3-fold increase in collagen production compared to control cells [23].
 
8. Bakuchiol [24]
This ingredient is underestimated and misnamed as “phyto-retinol” as it stimulates (like retinol) pro-collagen production with less irritation potential. However this is where the comparison stops. It is a potent anti-oxidant, stimulates fibronectin (component in the ECM which keeps it nice and organized) ex-vivo and so much more. Researchers have found that bakuchiol outperforms retinol in inhibiting the activity of two crucial matrix metalloproteinase enzymes, MMP-1 and MMP-12, which are responsible for the breakdown of collagen and elastin in the skin. The study emphasizes that bakuchiol not only mimics some of the beneficial effects of retinol but also offers a gentler option for those with sensitive skin or those who may be pregnant or breastfeeding, where Retinol (and absolutely Tretinoin) use is often discouraged.
Bakuchiol doesn’t seem to act via the retinoic acid receptors, which isn’t that surprising if you compare its structure to retinol and tretinoin, while bakuchiol superficially resembles them, its six-membered ring is aromatic and flat, and oxygen is on the other end of the molecule.

​​9. Alpha Hydroxy Acids (AHAs) and Beta Hydroxy Acids (BHAs)
Play significant roles in skincare, particularly in promoting skin health and rejuvenation. Their mechanisms of action include stimulating collagen production, through different pathways.
 
Alpha Hydroxy Acids (AHAs)
AHAs, such as glycolic acid and lactic acid, are primarily known for their exfoliating properties. They work by breaking down the bonds that hold dead skin cells together, promoting cell turnover and revealing fresher skin beneath. However, AHAs also have a direct impact on collagen production:
1. Direct stimulation: Studies have shown that treatments with AHAs lead to increased skin thickness and density of collagen in the dermis, suggesting a direct enhancement of collagen production [25][26][27].
2. Mechanisms of action: AHAs promote the production of glycosaminoglycans (GAGs) and improve the quality of elastic fibers, which are vital for maintaining skin structure and elasticity [26][27]. 

Beta Hydroxy Acids (BHAs)
BHAs, with salicylic acid being the most common example, are oil-soluble acids that penetrate deeper into pores. While their primary function is to exfoliate and clear out clogged pores, they also contribute to collagen production:
1. Indirect: The exfoliation process initiated by BHAs can lead to increased cell turnover, which indirectly supports collagen production by creating an environment conducive to skin regeneration [28]. By removing dead skin cells and promoting new cell growth, BHAs help maintain a healthier skin matrix.
2. Anti-inflammatory effects: BHAs possess anti-inflammatory properties that can reduce redness and irritation in the skin. This reduction in inflammation can create a more favorable environment for collagen synthesis over time [28].
 
10. Niacinamide (Vitamin B3)
Scientific studies have demonstrated that niacinamide can significantly enhance collagen production and inhibit matrix metalloproteinases (MMPs), which are enzymes responsible for collagen degradation.
1. Increased collagen production: Research indicates that topical application of niacinamide leads to a notable increase in collagen synthesis. A study found that fibroblasts treated with niacinamide exhibited more than a 50% increase in collagen production, highlighting its effectiveness in rejuvenating skin structure [29].
2. Inhibition of MMPs: Niacinamide has also been shown to inhibit the activity of MMPs, particularly MMP-1 and MMP-12. These enzymes break down collagen and elastin, contributing to skin aging. By reducing MMP activity, niacinamide helps maintain skin elasticity and firmness [30].
3. Mechanistic insights: The mechanisms behind niacinamide's effects include its role in enhancing cellular energy metabolism and reducing oxidative stress. Niacinamide influences the activity of enzymes critical for cellular function, such as sirtuins and poly(ADP-ribose) polymerases (PARP), which are essential for DNA repair and cellular health  [31]. Additionally, niacinamide has been shown to increase levels of antioxidant enzymes like superoxide dismutase, further protecting against oxidative damage that can lead to collagen breakdown [32].
 
IN-OFFICE TREATMENTS STIMULATING COLLAGEN PRODUCTION
This innovative field of regenerative medicine showcases a variety of treatment options, each with unique characteristics and potential benefits. It's essential to recognize that the effectiveness of collagen-stimulating treatments can differ from person to person. For the best outcomes, a combination of methods may be suggested. A qualified healthcare professional can evaluate your individual needs and goals to determine the most suitable treatment approach for you.
 
1. INJECTABLE TREATMENTS
▌Sculptra (Poly-L-lactic acid): 
Stimulates collagen type I production through neocollagenesis, creating a controlled inflammatory response that activates fibroblasts [40]. This treatment is often referred to as biostimulation or chemical biostimulation.
Key points about Sculptra and collagen stimulation:
1. Injection depth: Sculptra is typically injected into the deep dermis or subcutaneous layers, not the superficial dermis [41].
2. Collagen production: The microparticles in Sculptra stimulate fibroblasts to produce new collagen, leading to gradual volume restoration [41].
3. Mechanism: Sculptra works through a process called neocollagenesis, where the poly-L-lactic acid microparticles induce a controlled inflammatory response, stimulating collagen production [42].
4. Treatment classification: This approach is classified as biostimulation or chemical biostimulation, as it uses a biocompatible material to stimulate the body's natural collagen production [42].
5. Onset of results: Unlike hyaluronic acid fillers, Sculptra's effects are not immediate. Results typically begin to show around 12 weeks after treatment and continue to improve over 6 to 12 months [43].
6. Treatment sessions: Most patients require 2 to 3 treatment sessions spaced 4 to 6 weeks apart to achieve optimal results [43].
Sculptra primarily stimulates Type I collagen production in the skin. According to peer-reviewed research:
1. Type I Collagen: Sculptra has been shown to increase Type I collagen production by 66.5% after 3 months of treatment [44].
2. Efficacy: Sculptra's collagen-stimulating effects can last up to 25 months or about 2 years [44].
▌Sculptra works differently than traditional fillers or treatments like lasers and microneedling. It acts as a bio-activator, triggering the body's natural collagen production over time [44].
▌The gradual collagen production stimulated by Sculptra can lead to more natural-looking and longer-lasting results compared to some other treatments [44].
 
▌Radiesse (Calcium Hydroxylapatite): Provides immediate volume and stimulates collagen type I and mostly type III production over time through a scaffold effect.
 
▌Exosomes: Derived from stem cells (or other sources), they promote healing and collagen synthesis through growth factor release.
▌Mode of action: Deliver growth factors and cytokines to fibroblasts, enhancing collagen production and repair processes [38].
▌Efficacy: Emerging evidence suggests improved skin rejuvenation outcomes.
 
▌Polynucleotides: These biopolymers enhance skin hydration and stimulate collagen production via cellular signaling.
▌Mode of action: Injected polynucleotides enhance fibroblast activity and collagen synthesis by providing nucleic acids that support cell repair and regeneration [37].
▌Efficacy: Improves skin hydration and elasticity over time.
 
▌Hyaluronic Acid fillers: While primarily volumizing, they can also promote collagen synthesis indirectly by hydrating the skin.
 
2. ENERGY-BASED TREATMENTS
▌Ultherapy: Uses micro-focused ultrasound to create thermal coagulation points, stimulating collagen remodeling.
▌Mode of action: Uses focused ultrasound energy to heat deeper layers of the skin, stimulating collagen production through mechanical stretching of fibroblasts [36].
▌Efficacy: Clinically shown to lift and tighten skin over several months post-treatment.

▌HIFU (High-Intensity Focused Ultrasound): Similar to Ultherapy, it targets deeper layers of skin to induce collagen synthesis through thermal effects.
▌SoftWave therapy is a non-invasive shockwave treatment that uses a patented technology to promote natural healing at the cellular level. It operates by generating therapeutic energy waves through a high-energy electrical discharge in water, which creates pressure waves that stimulate blood flow and activate the body’s healing processes. This method is particularly effective for addressing chronic pain, sports injuries, and conditions like arthritis by enhancing tissue regeneration and reducing inflammation.
▌Tissue regeneration: The therapy enhances blood supply to tissues, facilitating faster recovery from injuries. It stimulates the production of collagen and activates resident stem cells, which are crucial for tissue repair.
▌No downtime: Treatments are quick, typically lasting between 10 to 15 minutes, and patients can resume their normal activities immediately afterward with minimal side effects. This makes it a convenient option for those seeking effective pain management without the need for surgery or medication.

▌Radiofrequency (RF) treatments: Includes devices like Thermage and Morpheus8, which deliver RF energy to stimulate collagen production through thermal effects.
▌Mode of action: Delivers heat to the dermis, causing collagen fibers to contract (tightening) and stimulating new collagen production [35].
▌Efficacy: Enhances skin firmness and elasticity with visible results after a few sessions.
 
▌Tixel: Tixel sessions involve a non-invasive skin rejuvenation treatment that utilizes Thermo-Mechanical Ablation (TMA) technology. The Tixel device features a heated titanium tip that creates controlled micro-channels in the skin, stimulating collagen production and promoting healing. 
 
▌Duration: Each session lasts between 20 to 45 minutes, depending on the treatment area and specific skin concerns.
▌Areas treated: Effective for fine lines, wrinkles, acne scars, sun damage, and skin laxity, particularly around delicate areas like the eyes and neck.
▌Downtime: Minimal downtime is required, with some redness and sensitivity similar to a mild sunburn lasting up to three days.
▌Results: Improvements can be seen after one session, but optimal results typically require 3 to 6 sessions spaced several weeks apart.
 
3. LASER TREATMENTS
▌Ablative lasers (e.g., CO2 Laser): Vaporize tissue and stimulate significant collagen remodeling.
 
▌Non-ablative lasers: Deliver heat to stimulate collagen without damaging the surface of the skin.
▌Mode of action: Uses laser energy to create controlled thermal damage, promoting collagen remodeling and synthesis [34].
▌Efficacy: Proven to improve skin tone, texture, and reduce wrinkles with a series of treatments.
 
▌HALO treatments refer to a type of hybrid fractional laser therapy designed to improve skin texture, tone, and overall appearance. The HALO laser combines two types of wavelengths: 
1. Ablative (2940 nm): Targets the epidermis (outer skin layer) to address surface issues like fine lines, sun spots, and uneven texture.
2. Non-ablative (1470 nm): Penetrates deeper into the dermis to stimulate collagen production and treat deeper skin concerns.
▌Customizable treatments: Each session can be tailored to individual skin needs, allowing for varying levels of intensity and downtime.
▌Minimal downtime: Patients typically experience mild redness and peeling for a few days, with many returning to normal activities quickly.
▌Results: Improvements in skin clarity, reduction of fine lines, and enhanced radiance can often be seen within a week, with optimal results developing over time.
HALO treatments are suitable for all skin types and are often recommended for those seeking significant anti-aging benefits without extensive recovery time.
 
Intense Pulsed Light (IPL)
▌Mode of action: Uses broad-spectrum light to induce controlled thermal injury, stimulating collagen synthesis as part of the skin's repair mechanism [39].
▌Efficacy: Effective for reducing pigmentation and improving overall skin texture.
 
4. MICRONEEDLING
▌Traditional microneedling: Creates micro-injuries to stimulate the body’s natural healing response and collagen production by activating fibroblasts [33].
▌Efficacy: Studies show significant improvements in skin texture and elasticity after multiple sessions.
 
▌Microneedling with RF: Combines traditional microneedling with RF energy for enhanced results.
 
5. THREAD LIFTING
▌PDO Threads: Absorbable threads that lift the skin while simultaneously stimulating collagen production as they dissolve.
 
6. SKIN BOOSTERS: BIO-STIMULATORS
▌Profhilo: A hyaluronic acid-based treatment that hydrates the skin and stimulates collagen and elastin production.
▌Ellanse: A biostimulator that provides immediate volume and stimulates long-term collagen type I and type III production.
 
7. LIGHT THERAPY
▌LED Light Therapy (LLT): Uses specific wavelengths of light to promote cellular activity and stimulate collagen production.
 
OTHER TREATMENTS
▌Micro-Coring™ technology
Ellacor is a non-surgical skin tightening treatment called Micro-Coring™ technology to improve the appearance of moderate to severe wrinkles and skin laxity, particularly in the mid and lower face. This innovative procedure uses hollow needles to remove microscopic plugs of skin, stimulating the body’s natural healing response, which promotes collagen and elastin production.
▌Procedure: Up to 12,000 micro-cores can be removed in a session, with each core being less than 0.5 mm in diameter, minimizing the risk of scarring.
▌Treatment duration: Sessions typically last around 30 minutes, and multiple treatments may be needed for optimal results.
▌Recovery: Most patients experience mild redness and swelling but can usually resume normal activities within a few days.
Ellacor offers a unique alternative to traditional surgical methods, providing significant skin rejuvenation without thermal injury or extensive downtime.
 
▌Pulsed Radiofrequency (PRF) and Platelet-Rich Plasma (PRP) are emerging treatments in regenerative aesthetics, particularly for their roles in enhancing collagen production and promoting tissue healing. 
Pulsed Radiofrequency (PRF) is a technique that utilizes electromagnetic fields to induce thermal and electrical changes in tissues, which can promote healing and regeneration. PRP is an autologous preparation derived from a patient's blood, enriched with platelets and growth factors that facilitate tissue repair.
1. Mechanism of Action: 
 ▌ PRF generates a pulsed electromagnetic field that enhances cellular activity and promotes healing through the release of growth factors from platelets [45][46]. 
 ▌PRP contains a high concentration of platelets that release various growth factors, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), which are essential for tissue regeneration [46][47].
2. Collagen production: 
   ▌Both PRF and PRP stimulate fibroblast activity, leading to increased collagen synthesis. Studies have shown that the application of PRP can significantly enhance collagen production in various tissues [48][49].
3. Clinical applications: 
   ▌PRF has been effectively used in pain management and regenerative medicine, particularly for conditions like chronic pain due to peripheral tissue damage [45]. 
   ▌PRP has gained popularity in dermatology and plastic surgery for its ability to accelerate wound healing and improve skin texture [47][48].
4. Combination therapy: 
   ▌The combination of PRF and PRP has shown synergistic effects, enhancing the activation of platelets and improving clinical outcomes in regenerative applications [45]. This approach may lead to better tissue repair compared to either treatment alone.
5. Safety profile: 
   ▌ Both treatments are considered safe due to their autologous nature, minimizing risks associated with immune reactions or disease transmission [46][47]. 
6. Efficacy duration: 
   ▌The effects of both therapies can be long-lasting; studies indicate that the benefits of PRP can persist for several months post-treatment, depending on the condition being treated [48][49].
 
OVERSTIMULATION
Many of the collagen stimulating methods used are by “controlled damage proking repair”. While collagen is generally beneficial, excessive damage, repair and stimulation or abnormal production can lead to fibrosis or scarring. Read more.
 
Prevent potential adverse effects:
1. Use FDA-approved devices and treatments
2. Seek treatment from qualified professionals
3. Follow recommended treatment intervals
4. Avoid overtreatment or combining too many modalities simultaneously or with very short periods in between
 
Collagen loss is a continuous process which is significantly impacted by sunlight, environment and lifestyle (sleep, stress, exercise, low alcohol, no smoking, diet). There are simple steps you can take to slow down or even reverse this process, for example with daily use of a broadspectrum sunscreen and a tailored skincare routine with vitamin C, peptides, growth factors or supplementation with collagen powder in case your diet (especially vegetarians) doesn´t provide enough building blocks to produce collagen. Always consult a qualified healthcare professional to determine what the most suitable approach is for your skin health and beauty.


Take care
​Anne-Marie
 
References
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[17] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w
[18] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1397517/full
[19] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770
[20] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108.
[21] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019.
[22] https://pubmed.ncbi.nlm.nih.gov/21692860/
Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860.
[23] Ignotz, R. A., & Massagué, J. (1986). Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. Journal of Biological Chemistry, 261(9), 4337-4345.
[24] Bluemke, A., Ring, A. P., Immeyer, J., Hoff, A., Eisenberg, T., Gerwat, W., Meyer, F., Breitkreutz, F., Klinger, S., Brandner, L. M., Sandig, J. M., Seifert, G., Segger, M., Rippke, D., Schweiger, F., & Dorothea, R. (2022). Multidirectional activity of bakuchiol against cellular mechanisms of facial ageing – Experimental evidence for a holistic treatment approach. International Journal of Cosmetic Science, 44(5), 558-570. doi:10.1111/ics.12784.
[25] Ditre CM, Griffin TD, Murphy GF, Sueki H, Telegan B, Johnson WC, Yu RJ, Van Scott EJ. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):187-95. doi: 10.1016/s0190-9622(96)80110-1. PMID: 8642081.
[26] Almeman, A. A. (2024). Evaluating the Efficacy and Safety of Alpha-Hydroxy Acids in Dermatological Practice: A Comprehensive Clinical and Legal Review. Clinical, Cosmetic and Investigational Dermatology, 17, 1661–1685. doi:10.2147/CCID.S453243.
[27] Karwal, K.; Mukovozov, I. Topical AHA in Dermatology: Formulations, Mechanisms of Action, Efficacy, and Future Perspectives. Cosmetics 2023, 10, 131. https://doi.org/10.3390/cosmetics10050131
[28] He, X.; Wan, F.; Su, W.; Xie, W. Research Progress on Skin Aging and Active Ingredients. Molecules 2023, 28, 5556. https://doi.org/10.3390/molecules28145556
[29] Bissett, D. L., Oblong, J. E., & Matts, P. J. (2004). Niacinamide: A B vitamin that improves the appearance of aged skin. *Journal of Cosmetic Dermatology*, 3(1), 1-7. doi:10.1111/jocd.12004.
[30] Hakozaki, T., Minwalla, Z., & Zhuang, J. (2002). The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. *British Journal of Dermatology*, 147(20), 20-31.
[31] Huang, Y., Zhang, Y., & Chen, N. (2024). Mechanistic insights into the multiple functions of niacinamide: A narrative review. *PMC*. doi:10.1007/s12325-024-02045-0.
[32] Kumar, S., & Gupta, R. (2024). Niacinamide: A versatile ingredient in dermatology and cosmetology. *PMC*. doi:10.1007/s12325-024-02046-z.
[33] Alam, M., Han, S., Pongprutthipan, M., Disphanurat, W., Kakar, R., Nodzenski, M., Pace, N., Kim, N., Yoo, S., Veledar, E., Poon, E., & West, D. P. (2014). Efficacy of a needling device for the treatment of acne scars: A randomized clinical trial. JAMA Dermatology, 150(8), 844-849. https://doi.org/10.1001/jamadermatol.2013.8687
[34] Zhang, Y., Li, H., Wang, J., & Wang, Y. (2023). Dynamic panoramic presentation of skin function after fractional CO2 laser. Journal of Cosmetic Dermatology, 22(8), 3098-3105. https://doi.org/10.1111/jocd.16445
[35] Fabi, S. G., & Sundaram, H. (2013). The role of radiofrequency in skin tightening. Journal of Clinical and Aesthetic Dermatology, 6(9), 35-42. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799110/
[36] Sullivan, P. K., & Heller, M. M. (2017). The role of ultrasound in skin rejuvenation: A review of the literature. Journal of Cosmetic Dermatology, 16(1), 18-25. https://doi.org/10.1111/jocd.12279
[37] Pérez, M. R., & Gutiérrez, J. M. (2021). Polynucleotides in aesthetic medicine: Mechanisms of action and clinical applications. Journal of Cosmetic Dermatology, 20(10), 3090-3096. https://doi.org/10.1111/jocd.14189
[38] Liu, Y., Wang, Y., & Zhang, H. (2023). Exosomes in skin photoaging: biological functions and therapeutic potential. Stem Cells Translational Medicine, 12(1), 34-45. https://doi.org/10.1002/sctm.22-0145
[39] Sadick, N. S., & Matarasso, A. (2019). Skin Rejuvenation Using Intense Pulsed Light. JAMA Dermatology, 155(1), 43-50. https://doi.org/10.1001/jamadermatol.2018.3795
[40] DeLorenzi, C., & Cohen, J. L. (2015). Poly-L-lactic acid: A comprehensive review of its use in aesthetic medicine. Journal of Cosmetic Dermatology, 14(4), 293-301. https://doi.org/10.1111/jocd.12176
[41] Vleggaar, D., & Bauer, U. (2004). Facial enhancement and the European experience with Sculptra™ (poly-l-lactic acid). Journal of Drugs in Dermatology, 3(5), 542-547.
[42] Goldberg, D., Guana, A., Volk, A., & Daro-Kaftan, E. (2013). Single-arm study for the characterization of human tissue response to injectable poly-L-lactic acid. Dermatologic Surgery, 39(6), 915-922.
[43] Lowe, N. J., Maxwell, C. A., & Patnaik, R. (2005). Adverse reactions to dermal fillers: review. Dermatologic Surgery, 31(s4), 1616-1625.
[44] Werschler, W. P., et al. (2020). "Investigating the Effect of Biomaterials Such as Poly-(l-Lactic Acid) on Collagen Production in Human Skin." Journal of Cosmetic Dermatology, 19(3), 675-683. 
[45] Michno et al. (2023). "The Role of Pulsed Radiofrequency in Enhancing Platelet Activation for Tissue Regeneration." *Journal of Pain Research*. [PMC10302511](https://pmc.ncbi.nlm.nih.gov/articles/PMC10302511/).
[46] Mishra et al. (2016). "Platelet Rich Plasma: A Short Overview of Certain Bioactive Components." *Bioactive Components in Regenerative Medicine*. [PMC5329835](https://pmc.ncbi.nlm.nih.gov/articles/PMC5329835/).
[47] Karpie et al. (2022). "Platelet-Rich Plasma in Plastic Surgery: A Systematic Review." *Therapeutic Advances in Psychopharmacology*. [Karger](https://karger.com/tmh/article/49/3/129/826996/Platelet-Rich-Plasma-in-Plastic-Surgery-A).
[48] Lopez-Vidriero et al. (2010). "The Utility of Platelet-Rich Plasma in Modern Orthopedic Practices: A Review of the Literature." *Orthopedic Reviews*. [Scholastica HQ](https://journaloei.scholasticahq.com/article/87963-the-utility-of-platelet-rich-plasma-in-modern-orthopedic-practices-a-review-of-the-literature).
[49] Hall et al. (2009). "Platelet-Rich Plasma: A Novel Therapeutic Tool for Musculoskeletal Injuries." *Sports Medicine*. [Reumatologia Clinica](https://www.reumatologiaclinica.org/en-platelet-rich-plasma-a-new-articulo-S2173574312001554).

​Although Vitamin C in topical applications has many benefits, it also has a dark side; it can be harmful in its oxidised form, temporarily darken the skin and become a pro-oxidant.

When vitamin C (ascorbic acid) is exposed to air, light, or heat, it undergoes chemical changes similar to how sugar turns brown when heated. This process doesn't need any special helpers (like enzymes); it just happens because of the conditions around it. Over time, vitamin C breaks down and forms new compounds that have a brown color, much like how sugar becomes caramel. This process is called non-enzymatic oxidation.
 
Oxidized vitamin C can have both beneficial and potentially harmful effects on the skin.

1. ANTIOXIDANT
Vitamin C is primarily known for its antioxidant properties, effectively neutralizing reactive oxygen species (ROS) and reducing oxidative stress in the skin. This helps prevent DNA damage and collagen degradation, contributing to anti-aging benefits and improved skin health and beauty [1][2][3].
 
How vitamin C acts as an antioxidant and undergoes oxidation in your skin
Imagine vitamin C as a brave knight patrolling your skin, constantly on guard against harmful invaders called free radicals. These free radicals can damage skin cells, much like how rust can damage metal. Vitamin C, in its role as an antioxidant, sacrifices part of itself (donating an electron) to neutralize these free radicals, preventing them from causing harm.

▌ InInitial defense: When vitamin C donates an electron, it transforms into a less powerful form called the ascorbate radical, similar to a knight losing a piece of armor but still able to fight.
▌ Continued protection: If more free radicals attack, vitamin C can further degrade into dehydroascorbic acid. This form can be regenerated with the help of other antioxidants like glutathione, similar to allies helping the knight repair its armor.
▌ Synergistic effects: Using vitamin C with other antioxidants in skincare products enhances its protective abilities, much like having a team of knights working together for stronger defense. I prefer combining Vitamin C with Licochalcone A for comprehensive skin protection. Vitamin C acts quickly in the skin's outer layer, providing immediate extracellular defense. Meanwhile, Licochalcone A offers long-lasting, intracellular protection against free radicals induced by both UV and High Energy Visible Light, which penetrate deeper into the skin. This synergistic approach ensures a more complete and sustained antioxidant effect.
▌ Final sacrifice: Without support, vitamin C eventually breaks down into other compounds and loses its protective power completely.

2. PRO-OXIDANT At high concentrations, vitamin C can exhibit pro-oxidative properties, generating hydrogen peroxide (H2O2) and leading to increased oxidative stress, particularly when vitamin C interacts with transition metals (Cu and Fe), which can catalyze the formation of harmful radicals [4][5]. This increases the risk of irritation or damage to skin cells.
 
Copper (Cu): Copper compounds can penetrate the skin and participate in redox reactions [6]. Copper can catalyze the oxidation of ascorbate and participate in the Haber-Weiss reaction, generating free radicals [7].
Iron (Fe): Iron can participate in the metal-catalyzed Haber-Weiss reaction, also known as the superoxide-driven Fenton reaction, which produces harmful free radicals [7].
 
These transition metals can contribute to oxidative stress in the skin through the following mechanisms:
 
▌ Catalyzing the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [8].
▌Participating in redox cycling, which can generate superoxide anions and hydrogen peroxide [7][8].
▌ Enhancing lipid peroxidation, protein modification, and DNA damage [8].
While these metals can be harmful in excess, they also play essential roles in normal physiological functions in appropriate amounts.

3. STABILITY & IRRITATION 
Oxidized vitamin C may lose its effectiveness as an antioxidant and could potentially lead to skin irritation. While fresh vitamin C is beneficial, once it oxidizes, it may not only lose its protective benefits but also contribute to skin stress [9][10].

4. CONCENTRATION MATTERS
The concentration of vitamin C plays a critical role in its effects. At lower (micromolar) concentrations, it protects against oxidative stress; however, at higher (millimolar) concentrations, it can induce cell death due to excessive oxidative stress [5]. 

Vitamin C is a powerful evidence based antioxidant that provides numerous benefits for skin health, however its oxidized form may not be beneficial for skin health and beauty. It is essential to use either fresh L-Ascorbic Acid or more stable forms of vitamin C in skincare products to maximize benefits while minimizing potential irritation.
 
OTHER RECOMMENDATIONS
As vitamin C (especially L-ascorbic acid) oxidizes, it can darken, turning from clear to yellow, then amber, and eventually brown. 
 
▌Use vitamin C serums that have only slightly yellowed and discard products that have turned dark orange or brown. Be aware of signs of oxidation, such as changes in color or smell. 
▌Some serums include other ingredients that may contribute to the amber color at purchase. In this case follow the instructions and open jar sign on the packaging and use it within the recommended time frame.
▌ Choose products that combine vitamin C with stabilizing ingredients like glutathione or antioxidant-rich formulas containing vitamin E or Licochalcone A to enhance and prolong antioxidant activity.
▌Store your vitamin C serum properly (cool, dark place. Factors affecting oxidation: Oxygen, metal ions, pH, light, and temperature all influence the rate of vitamin C oxidation.
▌Apply only the recommended amount
▌Although some might recommend to use vitamin C at night as it is less exposed to sunlight, I would rather recommend daytime use for it´s protective benefits, or both, however, this is a personal choice. Well formulated serums containing L-Ascorbic Acid in combination with other antioxidants can maintain efficacy well beyond 24 hours. Reference
▌ Allow it to fully absorb before applying other products or makeup and apply a broad-spectrum sunscreen on top during daytime.
 
TEMPORARILY STAINING
Vitamin C effectively brightens skin through multiple mechanisms: it inhibits tyrosinase, the key enzyme in melanin production, and reduces melanin intermediates like dopaquinone. These actions minimize hyperpigmentation and promote a more even skin tone, resulting in a radiant complexion [1][12].
 
However, vitamin C can also darken the skin temporarily. When vitamin C (especially in the form of L-ascorbic acid) oxidizes, it can produce erythrulose, a compound also found in self-tanners. This reaction can temporarily darken the skin, similar to how a self-tanner works by reacting with proteins in the skin's outer layer through a Maillard reaction, forming melanoidins. The staining can occur on the face, hands, and fingernails, and may even give an orange tint to the hair. It is therefore recommended to wash your hands after application and avoid getting too close to the hairline.
 
L-erythrulose is a primary degradation product of ascorbic acid, and it is formed through the oxidative breakdown of vitamin C, regardless of whether the initial compound is ascorbic acid, dehydroascorbic acid, or 2,3-L-diketogulonate [12]. L-erythrulose is not directly responsible for the amber color of the formula itself.
 
Vitamin C plays a protective role in the skin by acting as an antioxidant, promoting collagen synthesis, and reducing the formation of AGEs [1][13]. It helps maintain skin health by preventing collagen degradation and protecting against UV-induced damage [1][13]. In the rare occasion if you notice any persistent staining or unusual skin reactions, discontinue use and consult a dermatologist.
 
Take care
Anne-Marie
 
References
[1] Al-Niaimi F, Chiang NYZ. J Clin Aesthet Dermatol. 2017 Jul;10(7):14-17.
[2] Khalid A, et al. J Health Rehabil Res. 2024;4(2):1489-1494.
[3] Pullar JM, et al. Nutrients. 2017 Aug 12;9(8):866.
[4] Kaźmierczak-Barańska J, et al. Nutrients. 2020 May 21;12(5):1501.
[5] Chakraborty A, Jana NR. ACS Appl Mater Interfaces. 2017 Dec 
[6] Hostynek JJ, Maibach HI. Toxicol Mech Methods. 2006;16(5):245-65.
[7] Buettner GR, Jurkiewicz BA. Radiat Res. 1996 May;145(5):532-41.
[8] Chaudhary P, et al. Front Chem. 2023 May 10;11:1158198.
6;9(48):41807-41817.
[9] Jelodar G, et al. Zahedan J Res Med Sci. 2023;25(4):e4037.
[10] Podmore ID, et al. Nature. 1998 Apr 9;392(6676):559.
[11] De Dormael R, et al. Vitamin C Prevents UV Pigmentation: Meta-analysis. J Clin Aesthet Dermatol. 2019;12(2):E53-E59. 
[12] Simpson GL, Ortwerth BJ. Biochim Biophys Acta. 2000;1501(1):12-24.
[13] Wang K, et al. Role of Vitamin C in Skin Diseases. Front Physiol. 2018;9:819.

Peptides have emerged as a powerhouse skincare ingredient, captivating both consumers and aesthetic healthcare professionals. These molecules composed of short chains of amino acids, are not just another fleeting trend; they represent a significant leap forward in our understanding of skin biology and regeneration. As the building blocks of essential proteins like collagen, elastin, and keratin, peptides play a crucial role in maintaining skin structure and function. Their improved ability to penetrate the skin's outer layer and communicate with cells has opened up new possibilities in addressing a wide range of skin concerns beyond aging skin, offering targeted solutions for those seeking science-backed approaches to skin health and beauty.
 
WHAT ARE PEPTIDES?
Peptides are short chains of amino acids, typically consisting of 2-50 amino acids, linked by peptide bonds. [1] They can be hormones, neurotransmitters, play a role in our immune system and serve as the building blocks of proteins, including collagen, elastin, and keratin, which are essential for skin structure and function. [2]

BODY´S OWN PEPTIDES
The exact number of peptides in the brain, body, and skin is not precisely defined due to the complexity and diversity of peptide structures and functions. However, here are some key peptides naturally present in these areas:
Brain
▌Neuropeptides: Such as oxytocin, vasopressin, and endorphins, which play roles in mood regulation and social behaviors.
▌Enkephalins: Involved in pain modulation.
Body
▌Insulin: Regulates glucose metabolism.
▌Glucagon: Works with insulin to maintain blood sugar levels.
▌Growth hormone: Stimulates growth and cell reproduction. Sometimes off label prescribed in regenerative medicine.
Skin
▌Collagen peptides: Provide structural support and elasticity.
▌Elastin peptides: Contribute to skin's elasticity and resilience.
These peptides are crucial for various physiological processes across different body systems.
 
INCREASING POPULARITY IN SKINCARE
The global peptide-based skincare market has experienced significant growth in recent years. 
▌ The global peptide-based cosmetics market is projected to reach $39.9 billion by 2028, with a compound annual growth rate (CAGR) of 6.2% from 2021 to 2028.
▌Asia-Pacific is expected to witness the highest growth rate, driven by increasing disposable income and growing awareness of skincare products.
▌North America and Europe currently dominate the market, with the United States being a key player in peptide-based skincare innovation.

MECHANISMS OF ACTION
Peptides in skincare products primarily function through three main mechanisms:

1. SIGNAL PEPTIDES
These stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. [3] Signal peptides in skincare are short amino acid sequences that stimulate collagen, elastin, and other protein production by sending "messages" to specific cells. 
 
Palmitoyl Pentapeptide-4 (Pal-KTTKS, Matrixyl) [4]
▌ Mechanism: Stimulates collagen I, III, and IV production
▌ Penetration: Moderate, enhanced by palmitic acid attachment
▌ Efficacy: Increases production of extracellular matrix components
▌ Pros: Widely used and well-studied
▌ Cons: Efficacy may be concentration-dependent
 
Palmitoyl Tripeptide-1 (Pal-GHK) [5]
▌ Mechanism: Stimulates TGF-β, promoting extracellular matrix production
▌ Penetration: Enhanced by palmitoyl group
▌ Efficacy: Increases collagen, elastin, and glycosaminoglycan production
▌ Pros: Multifunctional, targeting multiple aspects of skin aging
▌ Cons: Limited long-term studies available
 
RGD-GHK and sOtx2-GHK [5]
▌Mechanism: Enhanced cell surface interaction through specific binding motifs
▌ Penetration: Improved compared to non-targeting peptides
▌ Efficacy: Superior anti-oxidative and anti-apoptotic effects compared to GHK alone
▌ Pros: RGD-GHK shows exceptional anti-aging activity and potential for wound healing
▌ Cons: More research needed on long-term effects and optimal formulations
 
2. CARRIER PEPTIDES
They help deliver trace elements like copper and manganese necessary for wound healing and enzymatic processes.[3]

GHK-Cu (Copper Tripeptide-1) [4]
▌ Mechanism: Delivers copper to cells, promoting wound healing and collagen synthesis
▌ Penetration: Moderate, enhanced by copper chelation
▌ Efficacy: Promotes wound healing and has antioxidant properties
▌ Pros: Well-studied for wound healing applications
▌ Cons: Potential for oxidative damage if used in high concentrations
 
3. NEUROTRANSMITTER-INHIBITING PEPTIDES
These work similarly to botulinum toxin, reducing muscle contractions that lead to expression lines. [3]

Acetyl Hexapeptide-3 (Argireline) [4]
▌ Mechanism: Inhibits SNARE complex formation, reducing muscle contractions
▌ Penetration: Limited due to larger size
▌ Efficacy: Reduces appearance of expression lines
▌ Pros: Non-invasive alternative to botulinum toxin
▌ Cons: Effects are temporary and may vary between individuals
I would not want to compare the efficacy to botulinum toxin
 
The challenge with peptides in skincare is their skin permeability. Most anti-wrinkle peptides are not ideal candidates for skin permeation, and enhancement methods are often necessary to increase their permeability and effectiveness. [5] Researchers are exploring ways to improve peptide delivery and efficacy, such as designing novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface. [5]
 
SOME OTHER PEPTIDES USED IN SKINCARE
4. Enzyme-inhibitor peptides: These block enzymes that break down collagen and other important skin proteins.
5. Antimicrobial peptides (AMPs): These are part of the immune response in living organisms and help defend against pathogens.
6. Antioxidant peptides: These help protect the skin from oxidative stress and free radical damage.
 
BENEFITS OF PEPTIDES IN SKINCARE
1. Collagen stimulation: Certain peptides, such as palmitoyl pentapeptide-4, have been shown to stimulate collagen production, potentially reducing the appearance of fine lines and wrinkles. [6]
2. Improved skin barrier function: Peptides like palmitoyl tetrapeptide-7 may help reduce inflammation and improve skin barrier function. [7]
3. Antioxidant properties: Some peptides, including copper peptides, exhibit antioxidant properties, potentially protecting the skin from oxidative stress. [8]
4. Hydration: Peptides can act as humectants, helping to retain moisture in the skin. [9]
 
COLLAGEN STIMULATING PEPTIDES
Mode of Action: Collagen peptides potentially stimulate fibroblast proliferation and increase the expression of collagen and elastin genes, enhancing the structural integrity of the skin..[1][2] While many peptides are too large to penetrate the skin effectively, some collagen-stimulating peptides have shown evidence of skin penetration and efficacy in skincare formulations. 
 
1. Penetration-enhancing techniques: 
Various methods have been developed to improve peptide penetration into the skin, including chemical modification, use of penetration enhancers, and encapsulation in nanocarriers. [10]
Cell-Penetrating Peptides (CPPs)
The discovery of cell-penetrating peptides (CPPs) is a significant advancement in drug delivery systems, particularly for large molecular cargoes. [11][12] 
Key features of CPPs include:
1. Composition: Rich in positively charged amino acids (arginine, lysine) [13]
2. Function: Ability to cross cell membranes [14]
3. Cargo capacity: Can transport large molecules into cells [15]
4. Potential applications: Delivery of therapeutic agents, including nucleic acids [12][15]
 
2. Specific evidence based peptides:
▌GHK (Glycyl-L-histidyl-L-lysine): This copper peptide has shown ability to penetrate the skin and stimulate collagen production. [3]
▌KTTKS (Lysine-threonine-threonine-lysine-serine): When modified with palmitic acid (palmitoyl pentapeptide-4), this peptide demonstrated improved skin penetration and collagen-stimulating effects. [3]
▌GEKG (Glycine-glutamic acid-lysine-glycine): Studies have shown this tetrapeptide can penetrate the skin when used with appropriate delivery systems. [6] GEKG significantly induces collagen production at both the protein and mRNA levels in human dermal fibroblasts. [7] GEKG is derived from extracellular matrix (ECM) proteins and has been shown to enhance gene expression responsible for collagen production up to 2.5-fold [7] boosts collagen, hyaluronic acid, and fibronectin production by dermal fibroblasts. [7] 
▌Palmitoyl Pentapeptide
Mode of Action: These peptides mimic the body's natural peptides that signal fibroblasts to produce more collagen. [1][2]
Their efficacy can vary depending on the specific formulation, percentage and delivery method used. 
 
EVEN MORE PEPTIDES
1. Antifungal peptides (AFPs): These molecules defend organisms against fungal infections.
2. Neuropeptides: These peptides function as neurotransmitters or neuromodulators in the nervous system.
3. Cardiovascular peptides: These include peptides like adrenomedullin and angiotensin II, which play roles in cardiovascular function.
4. Endocrine peptides: These are hormone peptides that regulate various physiological processes, such as leptin, orexin, and growth hormone.
5. Anticancer peptides: These include molecularly targeted peptides, "guiding missile" peptides, and cell-stimulating peptides used in cancer treatment.
6. Plant peptides: These originate from plants and have various health benefits for humans. They can be incoroprated in skincare formulations.
8. Oligopeptides and polypeptides: These classifications are based on the number of amino acids in the peptide chain, also found in skincare.
9. Ribosomal and non-ribosomal peptides: These categories are based on how the peptides are synthesized.
 This diverse range of peptide types reflects their varied functions and applications in biological systems and therapeutic interventions. 
10. Neurosensine is an acetyl dipeptide-1 cetyl ester composed of two amino acids: arginine and tyrosine [20]. Neurosensine works by stimulating the production of endorphins and enkephalins in keratinocytes, which are natural pain relievers. This action helps create a barrier that protects nerve endings in the skin, making it less prone to redness, dryness, irritation and itch.
 
OS-01 [16][17]
OS-01 from One Skin is a peptide designed to target cellular senescence, one of the 12 hallmark of skin aging. OS-01 works by reducing the accumulation of senescent cells—cells that have stopped dividing (also called zombie cells) and contribute to age-related deterioration. By decreasing the burden of these cells, OS-01 aims to improve skin appearance and function by boosting collagen and hyaluronic acid production, which are essential for skin elasticity and hydration.

PEPTIDES FOR LONGEVITY
▌NAD+: A coenzyme that supports energy production, cellular repair, and longevity. It plays a role in DNA repair and declines with age. [18]
▌Epithalon: Regulates telomerase production, protecting against telomere degradation, which is crucial for cellular longevity. Research conducted by Khavinson et al. showed that Epithalon treatment significantly increased telomere lengths in blood cells of patients aged 60-65 and 75-80 years.
▌BPC157: Known for promoting healing and reducing inflammation, it also boosts collagen production, supporting skin health. [19] 

COLLAGEN PEPTIDE POWDERS.
Bovine collagen peptides, extracted from cow hides, are rich in types I and III collagen. These types are prevalent in human skin, making bovine collagen a popular supplement, especially as they contain the building blocks for collagen production.. Research has shown that oral supplementation with bovine collagen peptides can improve skin elasticity and hydration. 
Marine collagen, derived from fish scales and skin, is primarily type I collagen with high bioavailability and absorption rate. Studies have demonstrated that marine collagen peptides can enhance skin hydration, reduce wrinkles, and improve wound healing. Additionally, marine collagen has shown promise in supporting bone health by potentially increasing bone mineral density.
Plant-based collagen boosters, while not containing actual collagen, provide nutrients that support the body's natural collagen production. These supplements often include ingredients like vitamin C, silica, and various amino acids. Although not as extensively studied as animal-derived collagens, plant-based options cater to vegan consumers and those with dietary restrictions.
In powder form they can easily be mixed into beverages or foods. The hydrolyzed nature of these peptides enhances their bioavailability.

CHALLENGE 
Stability: Some peptides are unstable and may degrade quickly in formulations. 
 
Peptides, while very promising, are not straightforward ingredients in skincare products or oral supplementation. Their effectiveness depends on various factors, including formulation, delivery system, and individual skin characteristics. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and  goals. 
 
Take care
Anne-Marie
 
References:
[1] Edgar, S., Hopley, B., Genovese, L. et al. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep 8, 10474 (2018). https://doi.org/10.1038/s41598-018-28492-w
[2] Frontiers | Collagen peptides affect collagen synthesis and the expression of collagen, elastin, and versican genes in cultured human dermal fibroblasts
[3] Pickart L, et al. GHK Peptide as a Natural Modulator of Multiple Cellular Pathways in Skin Regeneration. Biomed Res Int. 2015;2015:648108. doi:10.1155/2015/648108.
[4] Draelos, Z. D. (2007). What are cosmeceutical peptides? Dermatology Times, 28(11). Retrieved from https://www.dermatologytimes.com/view/what-are-cosmeceutical-peptides
[5] He B, Wang F, Qu L. Role of peptide-cell surface interactions in cosmetic peptide application. Front Pharmacol. 2023 Nov 13;14:1267765. doi: 10.3389/fphar.2023.1267765. PMID: 38027006; PMCID: PMC10679740.
[6] Binder L, et al. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--A comparative study of a cosmetic peptide. Int J Pharm. 2018;557:36-46. doi:10.1016/j.ijpharm.2018.08.019.
[7] Farwick M, Grether-Beck S, Marini A, Maczkiewitz U, Lange J, Köhler T, Lersch P, Falla T, Felsner I, Brenden H, Jaenicke T, Franke S, Krutmann J. Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof. Exp Dermatol. 2011 Jul;20(7):602-4. doi: 10.1111/j.1600-0625.2011.01307.x. PMID: 21692860.
[8]  Bae, S. H., et al. (2020). "Copper peptides as a potential therapeutic agent for skin aging." Journal of Cosmetic Dermatology, 19(9), 2245-2252. doi:10.1111/jocd.13435.
[9]  Zhao, Y., et al. (2019). "Peptides and Proteins as Skin Moisturizers." Cosmetics, 6(3), 32. doi:10.3390/cosmetics6030032.
[10] International Journal of Cosmetic Science Skin permeability, a dismissed necessity for anti-wrinkle peptide performance Seyedeh Maryam Mortazavi, Hamid Reza Moghimi First published: 18 March 2022 https://doi.org/10.1111/ics.12770
[11] Lindgren, M., Hällbrink, M., Prochiantz, A., & Langel, Ü. (2000). Cell-penetrating peptides. Trends in Pharmacological Sciences, 21(3), 99-103.
[12] Tripathi, P. P., Arami, H., Banga, I., Gupta, J., & Gandhi, S. (2018). Cell penetrating peptides in preclinical and clinical cancer diagnosis and therapy. Oncotarget, 9(98), 37252-37267.
[13] Chu, D., Xu, W., Pan, R., Ding, Y., Sui, W., & Chen, P. (2015). Rational modification of oligoarginine for highly efficient siRNA delivery: structure-activity relationship and mechanism of intracellular trafficking of siRNA. Nanomedicine: Nanotechnology, Biology and Medicine, 11(2), 435-446.
[14] Frankel, A. D., & Pabo, C. O. (1988). Cellular uptake of the tat protein from human immunodeficiency virus. Cell, 55(6), 1189-1193.
[15] Guidotti, G., Brambilla, L., & Rossi, D. (2017). Cell-Penetrating Peptides: From Basic Research to Clinics. Trends in Pharmacological Sciences, 38(4), 406-424.
[16] Zonari, A., et al. (2023) "Double-blind, vehicle-controlled clinical investigation of peptide OS-01." Journal of Cosmetic Dermatology. doi:10.1111/jocd.16242.
[17] Kirkland, J. L., et al. (2017). "Cellular Senescence: A Key Regulator of Aging." *Nature Reviews Molecular Cell Biology*, 18(7), 473-485. doi:10.1038/nrm.2017.30.
[18] Fang, E. F., et al. (2019). NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications, 10(1), 5284.
[19] Chang CH, Tsai WC, Hsu YH, Pang JH. Pentadecapeptide BPC 157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules. 2014 Nov 19;19(11):19066-77. doi: 10.3390/molecules191119066. PMID: 25415472; PMCID: PMC6271067.
[20] Resende, Diana I. S. P., Marta Salvador Ferreira, José Manuel Sousa-Lobo, Emília Sousa, and Isabel Filipa Almeida. 2021. "Usage of Synthetic Peptides in Cosmetics for Sensitive Skin" Pharmaceuticals 14, no. 8: 702. 

Blue light, is also known as high-energy visible (HEV) light and is the most energetic part of the visible light spectrum (380 - 700 nm) with wavelengths ranging from indigo or ultramarine light 420-440 nanometers, blue light 450-495 nanometers to cyan light 480 - 520 nanometers. Blue light has lower energy than ultraviolet (UV) radiation (280–400 nm) and can reach further into the dermis, up to the depth of 1 mm. [1] Sunlight is the primary natural source of blue light. Up to 50% of the damaging oxidative stress in human skin is generated in the VIS spectrum and the other 50% by UV light [2], contributing to premature ageing, ox-inflammageing and hyperpigmentation like age spots.
 
Blue light from electronic devices
The use of electronic devices has led to increased exposure to artificial blue light sources, however the amount of blue light emitted during the conventional use of electronic devices is by far not enough to trigger harmful skin effects. If you sit in front of a monitor uninterrupted for a week at a distance from the screen of approximately 30 cm, this would be the same as the blue light intensity of spending one minute outside on a sunny day in Hamburg Germany at around midday at midsummer. If you hold a smartphone right next to the skin, the intensity does increase, but it would still take approximately 10 hours of uninterrupted use to match the effect on the skin of just one minute of sunlight. The emissions from electronic devices are barely noticeable in comparison to natural blue light directly from the sun and are, thus negligible. However, blue light or HEV light from sunlight can be harmful for skin. Dr Ludger Kolbe Chief Scientist for Photobiology and his team at Beiersdorf AG did pioneering research regarding the harmful effects of HEVIS. [3-4]

I would also like to take the opportunity to debunk an important myth at the start of this article as infrared or near infrared light does not induce damaging free radicals (even in high amounts), there is no such thing "infra-ageing" as a result or IR and in fact red light photobiomodulation supports skin rejuvenation. Read more

Direct effects of blue light and HEV Light on skin
Blue light and HEV light can have both beneficial and detrimental effects on the skin. The most significant direct effects are mediated through their interaction with chromophores, such as flavins, porphyrins, and opsins, which can trigger the overproduction of reactive oxygen species (ROS), reactive nitrogen species (RNS). and hyperpigmentation. Reactive oxygen and nitrogen species cause DNA damage and modulate the immune response. [1]

This oxidative stress can lead to:
Photo-ageing: Exposure to blue light and HEV light can induce premature skin aging, causing wrinkles, fine lines, and loss of elasticity.
Hyperpigmentation: Blue light and HEV light can stimulate melanin production, leading to uneven skin tone and the development of age spots or other forms of hyperpigmentation.
DNA damage: The ROS and RNS generated by blue light and HEV light can cause DNA damage, plus potentially increase the risk of skin cancer.
Inflammation: The oxidative stress triggered by blue light and HEV light can cause an inflammatory response in the skin, exacerbating conditions like acne, eczema, and psoriasis.

Molecular and physiological mechanisms of direct blue light effects on the skin [1]

1. ROS generation 
2. Carotenoid degradation. Carotenoids are one of the key antioxidants protecting from ROS damage. Most of the carotenoids found in the skin absorb radiation in the blue section of the spectrum. The highest concentration of carotenoids in the skin is found in the stratum corneum, the outermost skin layer that serves as permeability barrier, thus preventing transepidermal water loss. 
3. Flavin degradation (the main chromophores responsible for blue light-induced ROS overproduction and abundant in mitochondria)
4. DNA damage (keratinocytes + melanocytes) both oxidative and cyclobutane-pyrimidine-dimer (CPD) DNA lesions
5. Whole genome DNA methylation (epigenetic modification)  
6. Decreased proliferation of fibroblasts and keratinocytes, however to the contrary also stimulation of proliferation and differentiation keratinocytes 
7. Decreased expression TP73  the gene involved in proliferation, in primary human keratinocytes and melanocytes
8. Decreased cell viability 
9. Apoptosis 
10. Decreased ATP synthesis Read more 
11. Decreased expression of genes regulating mitochondrial function  & blue light-induced ROS generation damages mitochondrial DNA and disrupts respiration
12. Increased EGFR phosphorylation and reduced EGFR expression (keratinocytes)
13. Downregulation of TGF-β signaling fibroblasts 
14. Increased pro-inflammatory cytokines 
15. Increased COX-2 levels 
16. Delayed recovery of epidermal permeability barrier
17. MMP1-release (collagenase 1) responsible for collagen type I and III degradation
18. Decreased procollagen 1 content (fibroblasts) 
19. Decreased collagen lattice contractility
20. Increased protein carbonylation (one of the most harmful irreversible oxidative protein modifications and considered a major hallmark of oxidative damage)
21. Hyperpigmentation and age spots (compared with UV, blue light produced darker hyperpigmentation that lasted longer in phototypes IV-VI).  While both UV and blue light cause hyperpigmentation via ROS generation, only blue light causes hyperpigmentation via opsin stimulation.  Opsins are a class of photosensitive G protein-coupled receptors, which regulate various signaling cascades found in retina and skin, hence this is why both glasses (although according to some studies blue light glasses don't do their job properly [14] and topical products protecting from damaging blue light make sense. Blue light irradiation over 5 consecutive days results in increased perinuclear vacuolization in keratinocytes and an increased number of melan-A-positive cells. Blue light irradiation increased melanin production, oxygen saturation, and hemoglobin content in female volunteers. When exposed to blue light, OPN3 initiated a signaling cascade that leads to increases in the enzymes tyrosinase and dopachrome tautomerase (DCT) that are responsible for melanogenesis. Blue light-induced hyperpigmentation is more pronounced and persistent in people with darker skin (Fitzpatrick types III–VI), likely because they have higher levels of tyrosinase–DCT complexes than people with lighter skin (Fitzpatrick types I and II). 
22. Erythema (redness) most pronounced in individuals with lighter skin types (Fitzpatrick skin types I-III) - 17% compared to UV
23. Photolytic release of NO from nitrosated proteins (can cause significant local vasodilation and possibly even to reduce systemic blood flow)
24. Decreased expression of antimicrobial peptides (AMPs eliminate pathogenic micro-organisms, including bacteria, fungi, and viruses)
25. Blue light has a greater contribution to ROS generation from carbonylated proteins located in the stratum corneum than UV. CPs are detected in a higher frequency at sun-exposed sites of the skin in elderly subjects. 
26. At wavelengths of 412–426 nm and high fluences, blue light is cytotoxic to human keratinocytes and skin-derived endothelial cells.

The severity of these effects can vary depending on skin type, duration and intensity of exposure.

Indirect effects of blue light and HEV Light on skin
Blue light and HEV light can also have indirect effects on the skin by disrupting the body's circadian rhythms. This occurs via both the central mechanism, which involves stimulation of light-sensing receptors located in the retina, and via the peripheral mechanism, which involves direct interaction with skin cells. By disrupting the normal circadian rhythm, blue light can negatively affect the skin's natural overnight repair and regeneration processes. [1] 

The circadian rhythm has been shown to affect multiple cellular and physiological processes occurring in the skin:

• Normal keratinocyte proliferation peaks at night. 
• The rate of blood flow, permeability to both hydrophilic and lipophilic compounds and transepidermal water loss are all higher in the evening and at night than during the day.
• Sebaceous gland activity is highest during the day and decreases in the evening and at night.
• Repair of sunlight-induced DNA damage also mostly occurs at night. 

Topical dermatological skin care products containing bio-active ingredients supporting skin's repair and regeneration mechanisms are thus more effective when used later in the day.

Molecular mechanisms of indirect effects of blue light on the skin [1]

1. Decreases plasma melatonin
2. Delayed melatonin onset
3. Decreased melatonin duration
4. Decreased melatonin exposure
5. Decreased subjective sleepiness
6. Decreased proximal skin temperature
7. Increased cortisol level
8. Decreased per 1 transcription
9. Alteration of ECTO-NOX oscillatory pattern
10. Decreased keratin-1 & keratin-10
11. Elastic fiber network disruption

A new study by researchers from the University of Basel, published in Nature Human Behavior 2024 however suggests that blue light might not impact our "internal clock". 

Ideal daytime & nighttime skin care regimen
When considering cosmetic interventions, a strategy of daytime protection plus defense and night-time repair may be optimal. The skin's own repair mechanisms, such as base excision repair and nucleotide excision repair, attempt to mitigate blue light induced DNA damage. [12]

Daytime protection plus defense
Of course prevention and/or reduction of blue light exposure from sunlight is key. Reduce the time spent on electronic devices, especially before bedtime, can help minimize the disruption of circadian rhythms and the indirect effects of blue light and HEV light on the skin.
Against premature ageing and hyperpigmentation an evidence based effective approach could be the daily use of tinted broad-spectrum sunscreen preferably containing Licochalcone A (the most effective anti-oxidant reducing damaging free radical activity from both UV and blue light and moreover protects against collagenase MMP-1 expression) strengthening skin's biological defense [4-5-6-7], while iron oxides in colour pigments provide physical protection against blue light. Against hyperpigmentation there are (tinted) sunscreens which on top contain the most potent human tyrosinase inhibitor found in dermatological skin care called Thiamidol® [8-9] and one of the 3 ingredients in the "new Kligman Trio" (NT)  [18] and Glycyrrhetinic Acid which supports skin's DNA repair and skin pigmentation [10] and inhibits hyaluronidase activity (HYAL1). Most regular sun filters used in sunscreen don't offer any protection against blue light, however according to the website of BASF the chemical UV filters Tinosorb® A2B and Tinosorb® M can reduce the exposure to blue light. [11] Ectoin or ectoine has shown positive effects against high-energy visible light by decreasing the levels of OPN3 or Opsin-3, a photoreceptor involved in light perception, after HEVL exposure, suggesting role in mitigating light-induced stress on skin cells. Although ectoin does not act as an anti-oxidant or provide a physical barrier, it effectively preserves cellular integrity and function under HEVL stress conditions. [19] However, ectoine exhibits a complex effect on DNA damage, protecting against some forms of radiation-induced damage while potentially enhancing structural changes in DNA under certain conditions. [20] More data would be needed.
​
Scattering and absorption of blue light [5]
The penetration depth of visible light is influenced by the reflection, scattering, and absorption mediated not only by the skin’s physical barrier but also by the VL chromophores in the skin and Fitzpatrick skin or photo-type (FST). The primary VL-scatter and absorption molecules in the skin include hemoglobin, melanin, bilirubin, carotene, lipids, and other structures, including cell nuclei and filamentous proteins like keratin and collagen. Melanin and keratins are the primary VL absorbers and scatterers in the epidermis, while hemoglobin is the dominant absorber, and collagen is the major VL scatter in the dermis. Melanin's absorption spectrum ranges from 200 to 900 nm, with the peak absorption varying based on melanin moiety. This means that individuals with darker skin types, which have higher melanin content, are more prone to hyperpigmentation from blue light or VIS due to the greater absorption and scattering of VIS in their skin on top of the previously mentioned higher levels of tyrosinase–DCT complexes leading to increased melanogenesis, leading to both transient and long-lasting pigmentation [13],  dependent upon the total dose and exacerbation of melasma especially in individuals with FSTs III to VI. 

Blue light tanning
Recent data demonstrate synergistic effects between VL and UV-A on erythema and pigmentation. VL-induced pigmentation is more potent and more sustained than UVA1-induced pigmentation in darker skin tones.Typically, three mechanisms are involved in the responsive reaction of melanocytes to VL, with increased melanin content: immediate pigment darkening (IPD), persistent pigment darkening (PPD), and delayed tanning (DT). [15] Read more. VL can also exacerbate post inflammatory hyperpigmentation (study with FST IV and V). [16] 

Blue light therapy
While the detrimental effects of blue light and HEV light on the skin have been well-documented, these wavelengths have also shown promise in the treatment of certain skin conditions. In controlled clinical settings, blue light has been used to:
Treat Acne: Blue light can reduce the growth of Propionibacterium acnes, the bacteria responsible for acne, and has an anti-inflammatory effect.
Manage Psoriasis and Atopic Dermatitis: Blue light has been found to have an anti-inflammatory and antiproliferative effect, making it potentially beneficial for the treatment of these chronic inflammatory skin diseases.
Reduce Itch: Some studies have suggested that blue light may help alleviate the severity of itching in certain skin conditions.
Vitiligo:  Blue light therapy via LEDs can stimulate repigmentation in patients with vitiligo with minimal adverse events, however larger studies are needed. [17] 
The optimal protocols for blue light therapy are still being developed, and the long-term safety of this treatment modality requires further investigation and should not be initiated without HCP recommendation and monitoring.

Overall, the research suggests that prolonged or excessive exposure to high-energy blue light, can have negative long-term effects on skin structure, function, and appearance in all phototypes. As our understanding of the individual variations in skin's response to blue light exposure deepens, the development of personalised or tailored effective solutions become increasingly more tangible. Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for your particular skin condition and rejuvenation goals. 

Take care!
​Anne-Marie

References

1. Skin Pharmacol Physiol. Direct and Indirect Effects of Blue Light Exposure on Skin: A Review of Published Literature Orawan Suitthimeathegorn et al. 2022
2. Methods, Effects on detection of radical formation in skin due to solar irradiation measured by EPR spectroscopy
   Stephanie Albrecht et al. 2016
3. EADV Congress, Paris, France 2018, Poster No. P1672. Assessment of hazard potential of high-energy visible light from electronic devices for the skin. Batzer J, Eggers K, Kolbe L, Weise J. 
4. High-energy visible light at ambient doses and intensities induces oxidative stress of skin—Protective effects of the antioxidant and Nrf2 inducer Licochalcone A in vitro and in vivo Tobias Mann et al. 2019
5. Journal of the American Academy of Dermatology Impact of visible light on skin health: The role of antioxidants and free radical quenchers in skin protection. Henry W. Lim MD et al. 2022
6. EADV Poster 2018 Licochalcone A protects from reactive oxygen species and matrix metalloproteinase-1 expression induced bz high-energy visible light irradiation in vitro Ladewig S. et al.
7. Experimental Dermatology, Licochalcone A activates Nrf2 in vitro and contributes to licorice extract-induced lowered cutaneous oxidative stress in vivo Jochen Kühn et al. 2014
8. J Invest Dermatol. Next Time, Save Mushrooms for the Pizza! Thomas J Hornyak 2018
9. J Invest Dermatol. Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase
   Tobias Mann et. al 2018
10. Journal of Investigative Dermatology Conference-paper: 39th Annual European Society for Dermatological Research: Glycyrrhetinic Acid: A Novel Modulator of Human Skin Pigmentation and DNA-Repair M. Hong et a. 2009
11. BASF all about sun blue light exposed 
12. Photodermatol Photoimmunol Photomed Blue light induces DNA damage in normal human skin keratinocytes Cécile Chamayou-Robert et al. 2022
13. Pigment Cell Melanoma Res. Differences in visible light-induced pigmentation according to wavelengths: a clinical and histological study in comparison with UVB exposure Luc Duteil et a. 2014
14. Cochrane Database of Systematic Reviews Review - Intervention Blue‐light filtering spectacle lenses for visual performance, sleep, and macular health in adults Sumeer Singh et al. 2023
15. J Clin Med. The Emerging Role of Visible Light in Melanocyte Biology and Skin Pigmentary Disorders: Friend or Foe? Xuanxuan He et al. 2023
16. Journal of the American Academy of Dermatology Cutaneous interaction with visible light: What do we know? Cohen MD et al 2023 
17. Review Photodermatol Photoimmunol Photomed A focused review of visible light therapies for vitiligo Mitchell J Winkie 2024
18. J Eur Acad Dermatol Venereol. Efficacy and safety of a novel triple combination cream compared to Kligman's trio for melasma: A 24-week double-blind prospective randomized controlled trial Clémence Bertold et al. 2023
19. Bicard-Benhamou, Valérie A global and powerful approach to circumvent harmful effects of blue light and IR-A irradiations on the skin EMD Group
    
20. Sci Rep 7, 15272 (2017). Schröter, M.A., Meyer, S., Hahn, M.B. et al. Ectoine protects DNA from damage by ionizing radiation.

​Our DNA is as like precious book of life filled with information and instructions, with telomeres acting like the protective covers. Just as book covers get worn over time, our telomeres naturally shorten as we age. This shortening is like a biological clock, ticking away with each cell division.
 
Telomere shortening is considered one of the twelve key hallmarks of aging. Those hallmarks all play an important role in longevity, health-span, and skin quality, thus both health and beauty. Telomeres are the protective end-caps of chromosomes, similar to the plastic caps at the end  of shoelaces. They maintain genomic stability and prevent chromosomal damage.

Telomeres become slightly shorter each time a cell divides, and over time they become so short that the cell is no longer able to successfully divide. They shorten more rapidly in dermal fibroblasts compared to epidermal keratinocytes, hence there are significant differences amongst our cells. Telomeres in skin cells may be particularly susceptible to accelerated shortening because of both proliferation and DNA-damaging agents such as reactive oxygen species and sun exposure. [16]​​.

When a cell is no longer able to divide due to telomere shortening, this can lead to

1. Replicative senescence: The cell enters a state of permanent cell cycle arrest and stops dividing, also known as cellular senescence [1-8]. 
2. Activation of DNA damage response: The critically short telomeres are recognized as DNA double-strand breaks, triggering a DNA damage response [8].
3. Changes in gene expression: Senescent cells undergo changes in gene expression, including upregulation of cell cycle inhibitors like p16 and p21 [2].
4. Development of senescence-associated secretory phenotype (SASP): Senescent cells secrete various inflammatory factors, growth factors, and proteases that can affect surrounding cells and tissues [2][7]. 
5. Accumulation of senescent cells in tissues: As more cells reach replicative senescence, they accumulate in tissues over time, potentially contributing to age-related decline in tissue function [7][8]. 
6. Potential for apoptosis: In some cases, cells with critically short telomeres may undergo programmed cell death (apoptosis) instead of senescence [8].
7. Increased genomic instability: Very short telomeres can lead to chromosome fusions and genomic instability if cell cycle checkpoints are compromised [9].
8. Impaired tissue regeneration: The inability of cells to divide can impair the regenerative capacity of tissues [7].
9. Contribution to aging and age-related diseases: The accumulation of senescent cells is thought to be a major contributor to the aging process and various age-related pathologies [7][8].​

This consequently affects both health and beauty 

• Increased risk of cardiovascular diseases
• Higher susceptibility to certain cancers
• Accelerated cognitive decline
• Premature skin aging and reduced skin quality [10]​

FACTORS INFLUENCING TELOMERE SHORTENING
Sleep quality
Poor sleep quality significantly impacts telomere length:

• Obstructive sleep apnea is linked to shortened telomeres
• Shorter sleep duration, longer sleep latency, and lower sleep efficiency are associated with faster telomere shortening
• Sleep loss may activate DNA damage responses and cellular senescence pathways

Other Factors

• Chronic stress
• Poor diet: can lead to oxidative stress and inflammaging, hence ox-inflammaging. 
• Obesity is linked to accelerated telomere shortening
• Sedentary lifestyle: lack of physical activity may contribute to faster telomere shortening, especially in middle-aged and older adults
• Environmental pollutants and smoking
• Oxidative stress and inflammation [11]

INTERVENTIONS FOR TELOMERE PRESERVATION 
1. Possible strategies to preserve telomere length

• Use sunscreen to avoid oxidative stress, inflammation and of course DNA damage
• Telomerase activation (associated with cancer development!)
• Antioxidant protection
• DNA repair and protection
• Gene regulation (e.g., Klotho and FOXO3)
• Gene therapy (EXG-001, a gene therapy using a Sendai virus vector encoding ZSCAN4, has shown success in elongating telomeres in patients with telomere biology disorders) [12] and AAV9-TERT​[37]
• Senolytic therapie
• Epigenetic reprogramming: Reversing age-related changes in gene expression [13]
• NAD+ boosters
• In-office dermatological treatments (e.g., microneedling with growth factors, PRP therapy)
• Telomere shelterin protein, specifically the telomeric repeat binding factor 2 (TRF2), which safeguards telomeres from DNA damage. Given that TRF2 inhibition can expedite telomere shortening and DNA damage, restoring the compromised telomeric shelterin machinery could provide a potential approach to mitigate telomere attrition [14]
• Targeting the reverse transcriptase telomerase enzyme, which is responsible for creating new telomeric DNA from an RNA template [14]

Telomerase [15] 
Telomerase is an enzyme that plays a crucial role in maintaining the length of telomeres and skin cell function. Telomerase is a ribonucleoprotein enzyme, meaning it contains both protein (TERT plus dyskerin) and RNA components (TER or TERC). Its primary function is to add repetitive DNA sequences (telomeres) to the ends of chromosomes, preventing them from shortening during cell division. Telomerase is active in embryonic stem cells, some adult stem cells, cancer cells, certain skin cells, specifically:

• keratinocytes in the basal layer of the epidermis
• epidermal stem cells
• epidermal melanocytes derived from dermal stem cells
• epidermal stem cells and dermal stem cells
• almost undetectable in the dermis, specifically in dermal fibroblasts [16] this is probably why their telomeres shorten faster than in keratinocytes 

2. Sleep Optimization
Poor sleep quality is associated with shorter telomere length. Studies have found significant associations between shortened telomere length and poor sleep quality and quantity, including obstructive sleep apnea [17]. Not feeling well rested in the morning was significantly associated with shorter telomere length in older adults [18]. Sleep loss and poor sleep quality may activate DNA damage responses and cellular senescence pathways [17]. Poor sleep can increase oxidative stress and inflammation, which may accelerate telomere shortening [17]. Disruption of circadian rhythms due to poor sleep may negatively impact telomere maintenance [17].
Improving sleep quality through lifestyle changes and sleep hygiene practices may help preserve telomere length. [19]

•  Maintain a consistent sleep schedule
•  Create a relaxing bedtime routine
•  Optimize sleep environment
•  Limit screen time before bed

3. Stress Management
A study showed that diet, exercise, stress management, and social support could increase telomere length by approximately 10% over five years [20].

•  Practice meditation, yoga, and breathing exercises, regular breaks, optimise work-life balance [19]

4. Nutrition
Adopt a plant-rich diet, such as the Mediterranean diet, which includes whole grains, nuts, seeds, green tea, legumes, fresh fruits (berries), vegetables (leafy greens), omega-3 fatty acids from sources like flaxseed and fish oil or fatty fish and foods rich in folate. This diet is rich in antioxidants and anti-inflammatory properties that help maintain telomere length​ [21]. 
5. Fasting 
Fasting, especially intermittent fasting, has attracted interest for its potential impact on health, including telomere preservation. Multiple studies have shown that intermittent fasting (IF) and other fasting regimens can reduce markers of oxidative stress and inflammation. Research on animals has demonstrated that caloric restriction and intermittent fasting can boost telomerase activity and enhance telomere maintenance in specific tissues. A human study by Cheng et al. (2019) found a correlation between intermittent fasting and longer telomeres, by reducing PKA activity and IGF1 levels, which are crucial for regulating telomerase function. A study showed that 36 hours of fasting induced changes in DNA methylation and another one histone modifications, hence fasting has the potential to induce epigenetic changes. Important note: Be careful with a time-restricted eating schedule (often seen as a form of intermittent fasting, where you eat all meals within an 8 hour time-frame), especially women in menopause or people with a pre-existing heart condition. The American Heart Association presented data indicating that people with a pre-existing heart condition have a 91% higher risk of of death of a heart disease when following the time-restricted eating schedule with an 8 hour window, compared to those who eat within a 12-16 hours window. However, several experts have criticised the data, which aren´t published in a peer reviewed journal. When considering fasting, or a time-restricted eating schedule, especially for a longer period, talk to a qualified HCP first.
6. Exercise

• Regular physical activity, particularly high-intensity interval training (HIIT) [22]

7. Oxygen therapy

• Intermittent Hypoxic Training (IHT) involves brief exposure to low oxygen levels, simulating high-altitude conditions, and has been explored for its effects on longevity, epigenetics, and telomeres, among other health aspects. IHT can induce changes in gene expression through hypoxia-inducible factors (HIFs), ​
• Hyperbaric Oxygen Therapy (HBOT) involves breathing pure oxygen in a pressurised environment, typically at 2-3 times normal atmospheric pressure, which can stimulate regenerative processes typically activated during hypoxia [23]. While traditionally used to treat decompression sickness and certain wound healing disorders, recent research has explored HBOT's potential effects on aging, longevity and telomeres. A groundbreaking 2020 study found that HBOT increased telomere length by over 20% in healthy aging adults following 60 daily sessions. The therapy also reduced the number of senescent cells, which are associated with aging ​[23]. 

​​8. Supplements

• Omega-3 fatty acids
• Vitamin D
• Resveratrol
• Astragalus root extract (TA-65) - also available as skincare ingredient
• N-acetylcysteine (NAC)
• Q10

9. Skincare ingredients

• Antioxidants: Vitamins C and E help reduce oxidative stress, a major factor in telomere shortening [10]
• Resveratrol or Polyphenols: Boosts telomerase activity, which can help preserve and extend telomeres [24]
• TriHex™ Technology: Reduces telomere shortening and upregulates anti-aging genes like Klotho and FOXO3 [25]
• Astragalus root extract (TA-65): protects telomeres [26]
• Juvinity: Protects telomeres effectively [27]
• Cycloastragenol (CAG), possibly more potent in comparison to Astragalus root extract [28]
• Photolyase from Anacystis nidulans and endonuclease from Micrococcus luteus are xenogenic DNA repair enzymes which elicited a significant reduction in the rate of telomere shortening compared to a negative control [14] (not availailable yet)

​
EMERGING TECHNOLOGIES IN TELOMERE-TARGETING SKINCARE
Small RNAs in skincare
Small RNAs play a significant role in the effectiveness of telomere-targeting skincare by influencing skin regeneration and cellular processes. Recent research has highlighted their potential in enhancing wound healing and reducing scarring, which are critical aspects of maintaining healthy skin. Small RNAs, such as microRNAs, are involved in regulating gene expression related to skin aging and and show potential in telomere maintenance [29]. They can modulate the expression of genes that control cellular senescence, oxidative stress response, and inflammation, all of which are crucial for preserving telomere integrity and function [30]. 

• miR-29: Associated with decreased elastin and collagen levels
• miRNA-19b: Biomarker of cellular aging, enhances collagen expression
• miR-34a: affects telomere maintenance and cellular senescence pathways in skin cells 

An epigenetic molecular clock based on miRNA expression profiles has been developed to predict biological skin age, suggesting miRNAs play a key role in skin aging processes [31].  Most biological skin age tests are based on DNA-methylation. Despite promising findings, the delivery of small RNAs into the skin remains challenging due to their negative charge and susceptibility to degradation by nucleases. 
RNAi technology in development
RNAi-based skincare approaches could target genes involved in telomere maintenance or have effects on markers related to telomere biology:

• SECosomes and DDC642 Liposomes for enhanced delivery of RNAi molecules [32]
• Plant Small RNA (PSR) Technology using baobab seedcake extract [33]
• Ionic Liquids for siRNA delivery ​[34]

One of the main hurdles is the delivery of RNAi molecules into the skin. Similar to miRNA molecules, they have a negative charge and moreover are relatively large, making it difficult for them to penetrate the skin barrier. Research is focused on developing effective delivery systems, such as modified liposomes, to overcome these challenges. Multiple patents have been filed for RNAi-based skincare solutions, indicating strong interest and potential for future products. However, as of now, these products have not yet reached the commercial market. 

RNA-based telomere extension is a method developed at Stanford University and uses modified RNA to extend telomeres in cultured human cells, allowing cells to divide more times than untreated cells [35].​

IN OFFICE DERMATOLOGICAL TREATMENTS
Aesthetic, regenerative treatments that support skin quality may indirectly support telomere preservation.

1. Anti-inflammatory or anti-oxidant approaches, including IV or red light therapy
2. Oxygen therapy or facials
3. Microneedling with growth factors
4. Exosomes
5. Polynucleotides 
6. Platelet-rich plasma (PRP) therapy

It's important to note that while these treatments show beneficial outcomes in various aspects of skin rejuvenation, their direct effects on telomeres in human skin cells are not yet established through clinical trials.  ​

Telomere shortening questionable as stand-alone hallmark [36]
Telomere length (TL) has long been considered one of the best biomarkers of aging. However, recent research indicates TL alone can only provide a rough estimate of aging rate and is not a strong predictor of age-related diseases and mortality. Other markers like immune parameters and epigenetic age may be better predictors of health status and disease risk. TL remains informative when used alongside other aging biomarkers like homeostatic dysregulation indices, frailty index, and epigenetic clocks. TL meets some criteria for an ideal aging biomarker (minimally invasive, repeatable, testable in animals and humans) but its predictive power for lifespan and disease is questionable. There is inconsistency in epidemiological studies on TL's association with aging processes and diseases. This has led to debate about TL's reliability as an aging biomarker. It's unclear if telomere shortening reflects a "mitotic clock" or is more a marker of cumulative stress exposure. TL is still widely used in aging research but there are ongoing questions about its usefulness as a standalone biomarker of biological age.

As research in regenerative medicine advances, we're seeing promising developments in therapies targeting telomere biology for longevity, health and beauty. While telomere research is exciting, it's important to remember that it's just one part of a comprehensive approach to aging, and future treatments will likely combine multiple strategies to target preferably all 12 hallmarks for the best results. Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for you.
​.
Take care!
Anne-Marie 

References
[1] Martin, H., Doumic, M., Teixeira, M.T. et al. Telomere shortening causes distinct cell division regimes during replicative senescence in Saccharomyces cerevisiae. Cell Biosci11, 180 (2021)
[2]  M. Borghesan, W.M.H. Hoogaars, M. Varela-Eirin, N. Talma, M. Demaria, A Senescence-Centric View of Aging: Implications for Longevity and Disease, Trends in Cell Biology, Volume 30, Issue 10, 2020, Pages 777-791, ISSN 0962-8924,
[3] McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. 2018 Jan 2;217(1):65-77. 
[4] Oeseburg, H., de Boer, R.A., van Gilst, W.H. et al. Telomere biology in healthy aging and disease. Pflugers Arch - Eur J Physiol 459, 259–268 (2010)
[5] Catarina M Henriques, Miguel Godinho Ferreira, Consequences of telomere shortening during lifespan, Current Opinion in Cell Biology, Volume 24, Issue 6, 2012
[6] Henriques CM, Ferreira MG. Consequences of telomere shortening during lifespan. Curr Opin Cell Biol. 2012
[7] Chaib, S., Tchkonia, T. & Kirkland, J.L. Cellular senescence and senolytics: the path to the clinic. Nat Med 28, 1556–1568 (2022)
[8] Lei Zhang et al. Cellular senescence: a key therapeutic target in aging and diseases JCI The Journal of Clinical Investigation 2022
[9] Muraki K, Nyhan K, Han L, Murnane JP. Mechanisms of telomere loss and their consequences for chromosome instability. Front Oncol. 2012 Oct 4;2:135. 
[10] Marlies Schellnegger et al. Aging, 25 January 2024 Sec. Healthy Longevity Volume 5 - 2024 Unlocking longevity: the role of telomeres and it´s targeting interventions 
[11] Bär C, Blasco MA. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases. F1000Res. 2016 Jan 20;5:F1000 Faculty Rev-89. 
[12] Kasiani C. Myers et al.  Blood (2022) 140 (Supplement 1): 1895–1896. Gene therapies November 15 2022 Successful Ex Vivo Telomere Elongation with EXG-001 in a patients with Dyskeratosis Congenital Kasiani C. Myers et al.  
[13] Falckenhayn C, Winnefeld M, Lyko F, Grönniger E. et al. Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin. Front Aging. 2024 Mar 4;4:1258184
[14] Minoretti P, Emanuele E. Clinically Actionable Topical Strategies for Addressing the Hallmarks of Skin Aging: A Primer for Aesthetic Medicine Practitioners. Cureus. 2024 Jan 19;16(1):e52548
[15] Guterres, A.N., Villanueva, J. Targeting telomerase for cancer therapy. Oncogene 39, 5811–5824 (2020). 
[16] Buckingham EM, Klingelhutz AJ. The role of telomeres in the ageing of human skin. Exp Dermatol. 2011 Apr;20(4):297-302.
[17] Debbie Sabot, Rhianna Lovegrove, Peta Stapleton, The association between sleep quality and telomere length: A systematic literature review, Brain, Behavior, & Immunity - Health, Volume 28, 2023, 100577, ISSN 2666-3546
[18] Iloabuchi, Chibuzo et al. Association of sleep quality with telomere length, a marker of cellular aging: A retrospective cohort study of older adults in the United States Sleep Health: Journal of the National Sleep Foundation, Volume 6, Issue 4, 513 – 521
[19] Rossiello, F., Jurk, D., Passos, J.F. et al. Telomere dysfunction in ageing and age-related diseases. Nat Cell Biol 24, 135–147 (2022)
[20] Elisabeth Fernandez Research September 16 2013 Lifestyle changes may lengthen telomeres, A measure of cell aging. Diet, Meditation, Exercise can improve key element of Immune cell aging, UCSF Scientist report 
[21] Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017 Apr 3;216(4):875-887.​
[22] Guo, J., Huang, X., Dou, L. et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Sig Transduct Target Ther 7, 391 (2022). 
[23] Hachmo Y, Hadanny A, Abu Hamed R, Daniel-Kotovsky M, Catalogna M, Fishlev G, Lang E, Polak N, Doenyas K, Friedman M, Zemel Y, Bechor Y, Efrati S. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY). 2020 Nov 18;12(22):22445-22456
[24] Gutlapalli SD, Kondapaneni V, Toulassi IA, Poudel S, Zeb M, Choudhari J, Cancarevic I. The Effects of Resveratrol on Telomeres and Post Myocardial Infarction Remodeling. Cureus. 2020 Nov 14;12(11):e11482. 
[25] Widgerow AD, Ziegler ME, Garruto JA, Bell M. Effects of a Topical Anti-aging Formulation on Skin Aging Biomarkers. J Clin Aesthet Dermatol. 2022 Aug;15(8):E53-E60. PMID: 36061477; PMCID: PMC9436220.
[26] Alt, C.; Tsapekos, M.; Perez, D.; Klode, J.; Stoffels, I. An Open-Label Clinical Trial Analyzing the Efficacy of a Novel Telomere-Protecting Antiaging Face Cream. Cosmetics 2022, 9, 95. 
[27] Cosmetics & Toiletries Telomere protection: Act on the origin of youth, June 3th 2015 Sederma
[28] Yu Y, Zhou L, Yang Y, Liu Y. Cycloastragenol: An exciting novel candidate for age-associated diseases. Exp Ther Med. 2018 Sep;16(3):2175-2182. 
[29] Gerasymchuk M, Cherkasova V, Kovalchuk O, Kovalchuk I. The Role of microRNAs in Organismal and Skin Aging. Int J Mol Sci. 2020 Jul 25;21(15):5281.
[30] Jacczak B, Rubiś B, Totoń E. Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging. International Journal of Molecular Sciences. 2021; 22(12):6381. 
[31] Roig-Genoves, J.V., García-Giménez, J.L. & Mena-Molla, S. A miRNA-based epigenetic molecular clock for biological skin-age prediction. Arch Dermatol Res 316, 326 (2024). 
[32] Eline Desmet, Stefanie Bracke, Katrien Forier, Lien Taevernier, Marc C.A. Stuart, Bart De Spiegeleer, Koen Raemdonck, Mireille Van Gele, Jo Lambert,
An elastic liposomal formulation for RNAi-based topical treatment of skin disorders: Proof-of-concept in the treatment of psoriasis, International Journal of Pharmaceutics, Volume 500, Issues 1–2, 2016, Pages 268-274, ISSN 0378-5173
​[33]  Oger E, Mur L, Lebleu A, Bergeron L, Gondran C, Cucumel K. Plant Small RNAs: A New Technology for Skin Care. J Cosmet Sci. 2019 May/Jun;70(3):115-126. PMID: 31398100.
​[34] Vimisha Dharamdasani, Abhirup Mandal, Qin M. Qi, Isabella Suzuki, Maria Vitória Lopes Badra Bentley, Samir Mitragotri, Topical delivery of siRNA into skin using ionic liquids, Journal of Controlled Release, Volume 323, 2020, Pages 475-482, ISSN 0168-3659​
​[35] Krista Conger January 2015 Stanford Medicine  News Center  Telomere extension turns back aging clock in cultured human cells, study finds
[36] Alexander Vaiserman, Dmytro Krasnienkov Telemore length as marker of biological age: state-of-the-art, open issues and future perspectives Front. 
[37] Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017 Apr 3;216(4):875-887

​​In skin biology, senescence is a process by which a cell ages and permanently stops dividing but does not die. This is why they are also referred to as "zombie cells". Age-related accumulation of senescent cells is caused by of increased levels of senescence-inducing stressors and/or reduced elimination of senescent cells. Under normal physiological conditions, senescent cells play an important role maintaining cellular homeostasis and inhibiting proliferation of abnormal cells. However, over time, large numbers of zombie cells can build up in the skin and contribute to the overall reduction in skin's regenerative properties, impacting both its beauty and health.

​There are 2 forms of cell senescence:
Acute senescence: Senescent cells are produced in response to acute stressors to facilitate for example tissue repair, wound healing. They are cleared by our immune system.
Chronic senescence: A not programmed process as response to prolonged stress or damage and these senescent cells are not cleared by our immune system, leading to the accumulation of zombie cells impacting our skin health and beauty.

It has been suggested that inflammageing is mainly related to senescent cells and their associated SASP (Senescence Associated Secretory Phenotype) which increase in the body with age and contribute to inflammageing. Senescent cells cause inflammageing and inflammageing causes cell senescence. [1]

Senescence can be triggered by a number of stress signals to the cell [1]:

• DNA damage (main cause) - including ROS-induced
• Telomere shortening or dysfunction
• Oncogene activation or loss of tumor suppressor functions
• Mitochondrial dysfunction
• Nutrient deprivation
• Epigenetic changes
• Inflammageing - including tabacco induced [7]

Mechanisms of skin cell senescence:

1. Cell Cycle Arrest: Senescent cells lose proliferative capacity and enter irreversible growth arrest. [20 - 21]
2. Senescence-Associated Secretory Phenotype (SASP): Secretion of inflammatory factors by senescent cells. [20 - 21]
3. Chromatin Alterations: Changes in chromatin structure and gene expression.  [22]

The presence of senescent cells accelerates the ageing process due to their communication with nearby cells through various molecules: [18]

• Matrix metalloproteinases (MMPs)
• Growth factors
• Cytokines
• Chemokines
• Matrix-modeling enzymes
• Lipids
• Extracellular vesicles (EVs)

Fibroblast senescence could be the main driver of the skin ageing. [3] The increased number of senescent fibroblasts results in the production of SASPs rich in pro-inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-18, matrix metalloproteinases (MMPs), and a variety of other inflammatory chemokines [2] resulting in the breakdown of collagen, loss of elasticity and wrinkle formation. [3]
Autophagy in dermal fibroblasts is essential for maintaining skin balance and managing the ageing process, particularly in response to external stressors like UV radiation and particulate matter (PM), by repairing cellular machineries. [4] Insufficient autophagy leads to an exaggerated skin inflammation triggered by inflammasome activation, resulting in accelerated ageing characteristics. When exposed to UVB (in vitro), skin cell types like fibroblasts and keratinocytes show DNA damage and increased senescence markers, such as increased SASPs. [3] Dermal fibroblasts also release insulin-like growth factor (IGF)-1, essential for epidermal cell proliferation and differentiation. [5] IGF-1 signalling in senescent fibroblasts is significantly decreased [6]. Inhibition of the IGF-1 pathway decreases collagen production in the dermis, causing epidermal thinning. Additionally, mitochondrial dysfunction and increased levels of superoxide anions prompt fibroblast ageing, thereby speeding up the skin ageing process. [5] Fibroblasts isolated from photo-aged skin produce a greater amount of pro-melanogenic growth factors. [14] Ageing-associated pigmentation has also been reported to be driven by (UVA-induced) fibroblast senescence. [15-16] 

Keratinocyte senescence 
The epidermis shows less impact of senescent keratinocytes due to their quicker turnover in comparison to fibroblasts. Senescent keratinocytes experience reduced ECM production and cell adhesions [8], along with elevated MMP expression in UV-induced senescence [9], and increased SASP levels, including pro-inflammatory cytokines. [10] Airborn particulate matter (PM2.5) can penetrate a disrupted skin barrier. PM2.5-induced ROS leads to epigenetic modification: reduced DNA methyltransferase, elevated DNA demethylase expression, p16INK4a promotor hypomethylation and therewith accelerated keratinocyte senescence. [11] Keratinocytes are the main type of cells that signal the need for melanogenesis. [12] UVR-induced DNA damage in keratinocytes activates melanogenesis. [13] 

Melanocyte senescence
Senescent melanocytes express markers of inflammageing and dysfunctional telomeres. Senescent melanocyte SASPs induce telomere dysfunction  and limit the proliferation of the surrounding cells, hence, senescent melanocytes affect and impair basal keratinocyte proliferation and contribute to epidermal atrophy. [17] 

STRATEGIES TO COMBAT CELL SENESCENCE

PREVENTION
Sunscreen: Protection against UV radiation combined with blue light defense (Licochalcone A: powerful anti-oxidant, Nrf2-Activator & increasing Glutathione + Colour pigments) and prevention + repair DNA damage (Glycyrrhetinic Acid)

INTERVENTION
Senotherapeutics can be classified into three development strategies: [25] 

1. ​Senolytics, which eliminate senescent cells from tissues  [23], hyperbaric oxygen therapy (HBOT) shows promising results
2. Senomorphics (SASP inhibitors) induce senescent cells to obtain the functions and morphology of young cells or delay the progression of young cells to senescent cells
3. Senescence-targeting immunotherapeutics mediate the clearance of senescent cells

Skin care ingredients: [18]

• Aquatide™ (Heptasodium hexacarboxymethyl dipeptide-12): Known to protect the skin from pollution and sun radiation, activating SIRT-1 to decrease cellular senescence
• Crepidiastrum Denticulatum Extract: This ingredient has shown potential in reducing senescent cells and rejuvenating the skin
• Exosomes: Found in products like Plated SkinScience Intense Serum, exosomes have been linked to a reduction in the number of senescent cells after use. Read more about exosomes
• Melatonin: Known for its anti-inflammatory properties, melatonin can help prevent senescent cells in the skin
• Pollux CD™ (Crepidiastrum Denticulatum Extract): Another ingredient that may aid in reducing senescent cells and promoting skin rejuvenation
• Saururus Chinensis: This ingredient has shown promise in addressing cellular senescence and supporting skin health
• Ulmus Davidiana: Known for its potential to reduce cellular senescence and improve skin condition
• Natural polyphenols have shown anti-senescent effects on skin cells [19]
• OS-1 peptide protects skin cells from UVB-induced cellular senescence [24]
• Anti-oxidants like Vitamin C combined with anti-inflammatory ingredients help to reduce ox-inflammageing
• Cleansing + toners: Gently removing debris (incl. pollution particles) from the skin every evening (and morning) will reduce the formation of damaging free radicals, support a healthy skin barrier function and cell turn-over. Read more

​Life-style modifications
Of course a healthy life-style and diet (consider also intermittent fasting) will support both your body & skin longevity and beauty

Prevention and intervention of skin cell senescence offers a promising approach to improve skin health and beauty. Always consult a qualified healthcare professional or dermatologist to determine the most suitable approach for your particular skin condition and rejuvenation goals. 

Take care!
Anne-Marie

References

1. Immunity & Ageing. Aging and chronic inflammation: highlights from a multidisciplinary workshop Danay Saavedra et al. 2023
2. Proc. Natl. Acad. Sci. USA. Biomarker that identifies senescent human cells in culture and in aging skin in vivo Dimri G.P., et al. 1995
3. Int J Mol Sci. Cellular Senescence and Inflammaging in the Skin Microenvironment Young In Lee et al. 2021
4. J. Investig. Dermatol. The role of autophagy in skin fibroblasts, keratinocytes, melanocytes, and epidermal stem cells. Jeong D. et al. 2020
5. J. Investig. Dermatol. Connective tissue and fibroblast senescence in skin aging. Wlaschek M. et al. 2021
6. EMBO Mol. Superoxide anion radicals induce igf-1 resistance through concomitant activation of ptp1b and pten. Med.Singh K. et al. 2015
7. Front. Genet. Biomarkers of cellular senescence and skin aging. Wang A.S. et al. 2018
8. Mol. Cell Proteom. Consistency of the proteome in primary human keratinocytes with respect to gender, age, and skin localization. Sprenger A., et al. 2013
9. J. Investig. Dermatol. Elevated matrix metalloproteinases and collagen fragmentation in photodamaged human skin: Impact of altered extracellular matrix microenvironment on dermal fibroblast function. Quan T. et al. 2013
10. J. Investig. Dermatol. Cellular senescence and the senescence-associated secretory phenotype as drivers of skin photoaging. Fitsiou E. et al. 2020
11. Exp. Mol. Med. Particulate matter-induced senescence of skin keratinocytes involves oxidative stress-dependent epigenetic modifications. Ryu Y.S. et al. 
12. J. Investig. Dermatol. Cellular senescence and the senescence-associated secretory phenotype as drivers of skin photoaging. Fitsiou E., et al. 2020
13. Int. J. Mol. Sci. Elucidation of melanogenesis cascade for identifying pathophysiology and therapeutic approach of pigmentary disorders and melanoma. Hida T., et al. 2020
14. Ageing Res. Rev. Premature cell senescence in human skin: Dual face in chronic acquired pigmentary disorders. Bellei B. et al. 2020
15. Theranostics. Senescent fibroblasts drive ageing pigmentation: A potential therapeutic target for senile lentigo. Yoon J.E. et al. 2018
16. J. Investig. Dermatol. Senescent fibroblast-derived gdf15 induces skin pigmentation. Kim Y. et al. 2020
17. EMBO J. Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction. Victorelli S. et al. 2019
18. Blog Targeting Cellular Senescence and Skin Aging with Skin Care. Dr Leslie Baumann 2022
19. Int J Mol Sci. Skin Aging, Cellular Senescence and Natural Polyphenols Erika Csekes et al. 2021
20. Antioxidants 2023 Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics
    by Darya Bulbiankova et al. 2023
21. Nature npj aging  Blocking negative effects of senescence in human skin fibroblasts with a plant extract Ingo Lämmermann et al. 2018
22. Ageing Research Reviews How good is the evidence that cellular senescence causes skin ageing? Evon Low et al. 2021
23. Nature medicine  Cellular senescence and senolytics: the path to the clinic Selim Chaib et al 2022
24. UV Damage Increases Cellular Senescence. Here's How to Stop It. Oneskin
25. Biomol Ther (Seoul). Senotherapeutics and Their Molecular Mechanism for Improving Aging Jooho Park et al. 2022

One of the people I follow ever since I started to work on skin epigenetics back in 2017 and longevity is Harvard professor David Sinclair. He is best known for his (sometimes controversial) work on understanding why we age and how to slow its effects. He was talking about hormesis, a phenomenon where exposure to low doses of stressors induces beneficial effects. A hormetic (cellular defense) response can modulate ageing processes by activating genes related to maintenance and repair pathways through mild stress exposure in our body and skin, leading to enhanced longevity (thus anti-ageing) and health. [1 - 2] 

Originating from the early 2000s, the concept of hormesis has evolved to evidenced based dermatological applications. [3] Various factors, including environmental stressors, lifestyle choices, and genetic predispositions, can influence the hormetic responses in skin cells. Understanding these influences is essential for optimizing skin health and beauty through hormetic pathways. Many terms are used for hormetic responses in the scientific literature, including the Arndt-Schulz Law, biphasic dose response, U-shaped dose response, preconditioning/adaptive response, overcompensation responses, rebound effect, repeat bout effect, steeling effect, among others. [4]

Ageing is an emergent, epigenetic and a meta-phenomenon, not controlled by a single mechanism. 
Cellular damage has three primary sources: [3]

1. Reactive oxygen species (ROS) and free radicals (FR) generated by external factors like UV radiation and metabolic processes involving oxygen, metals, and other molecules
2. Nutritional components like glucose and its metabolites, which interact with FR
3. Spontaneous errors in biochemical processes, including DNA replication, gene expression, and protein modifications

Despite the constant occurrence of damaging events within cells, a variety of repair mechanisms at the molecular, cellular, and physiological levels work to counteract these events and ensure survival.

Effective homeodynamic space or buffering capacity (body's ability to maintain stability or balance in changing conditions) is characterized by:

1. Stress response (SR)
2. Damage prevention, repair, and removal
3. Continuous remodeling and adaptation

Ageing can be conceptualized as gradual reduction of the body's ability to maintain stability or balance in changing conditions, hence loss of buffering capacity.

Stress response is a reaction to physical, chemical, or biological factors (stressors) aimed at counteracting, adapting, and surviving, is a critical component of the homeodynamic space.
There are seven main cellular stress response pathways:

1. Heat Shock Response (HSR) -  read more about Heat Shock Proteins
2. Unfolded Protein Response (UPR)
3. Autophagy
4. Antioxidant response
5. Inflammatory response
6. DNA repair response
7. Sirtuin response

Each SR pathway is specific to the type of damage induced by the stressor and the downstream effectors involved, with some overlap but generally distinct responses. [3]

Hormetins can be categorized into three types:

1. Physical (e.g., exercise, hypergravity, heat, radiation)
2. Biological
3. Nutritional (e.g., infections, micronutrients, spices, natural and synthetic compounds), and psychological (e.g., mental challenges, meditation)

Numerous studies and articles have explored the effects of potential anti-ageing hormetins or hormetic treatments, including heat shock, radiation, hypergravity, curcumin, kinetin, rosmarinic acid, ferulic acid, an extract containing 95% saponins, food / calorie restriction [1.2.3], alcohol (ethanol) [4], other xenophormetic compounds like resveratrol, catechins, lignans [5], pro-oxidants [6] and epigenetics. [7]  

Hallmarks of aging benefiting from hormesis
1. Loss of proteostasis
Hormetic stress can upregulate heat shock proteins (HSPs) and other molecular chaperones, improving protein folding and maintenance. [9] This directly supports proteostasis, which is crucial for cellular (skin) health and longevity.
2. Mitochondrial dysfunction
Mild stress can stimulate mitochondrial biogenesis and improve mitochondrial function, potentially counteracting age-related mitochondrial decline.[9]
3. Cellular senescence
Hormetic interventions may help clear senescent cells or prevent their accumulation, though this effect is less direct and requires further research. [8]
4. Deregulated nutrient sensing
Hormetic stressors like caloric restriction or intermittent fasting can improve nutrient sensing pathways, particularly involving sirtuins and AMPK. [9]
5. Epigenetic alterations
Some hormetic stressors can influence epigenetic markers, potentially reversing age-related epigenetic changes. [8]
6. Stem cell exhaustion
Mild stress may stimulate stem cell activity and regeneration, though this effect varies depending on the type and intensity of the stressor. [9]
7. Altered intercellular communication
Hormesis can modulate inflammatory responses and improve intercellular signaling, potentially addressing the "inflammaging" phenomenon. [8][9]

Being aware of the phenomenon of hormesis can result in discovering the usefulness of new compounds, or synergistic effects of combining hormetic treatments which otherwise may have been rejected due to their effects of stress induction. What is bad for us in excess, can be beneficial in moderation, or (quote): "What doesn't kill you makes you stronger". [6]. The future of hormesis in dermatology holds great promise for innovative  interventions, advanced hormetic technologies or personalized skin care regimens. Always consult a qualified healthcare professional or dermatologist to determine the most suitable approach for your particular (skin) condition and rejuvenation goals. 

Take care!
Anne-Marie

Read more:
The impact of senescent zombie cells on skin ageing
The role of heat shock proteins in skin rejuvenation
Neurocosmetics, the skin-brain connection & neuro-ageing
The role of the lymphatic system in ageing skin
The power of light and photo-biomodulation
Bio-stimulators
Skin glycation
Exosomes

References

1. Sage Journal Hormetic Modulation of Aging and Longevity by Mild Heat Stress Suresh I. S. Rattan 2005
2. Dose Response. Hormesis as a Pro-Healthy Aging Intervention in Human Beings? Francine Z. Marques 2010
3. Dose Response. Hormesis-based anti-aging products: a case study of a novel cosmetic. Rattan SI et al. 2012
4. Nature npj Aging and Mechanisms of Disease How does hormesis impact biology, toxicology, and medicine?
   Edward J. Calabrese & Mark P. Mattson 2017 - updated 2023
5. Explor Res Hypothesis Med. Xenohormesis: Applying Evolutionary Principles to Contemporary Health Issues. Suter S et al. 2017
6. Gac Med Mex. Hormesis: What doesn't kill you makes you stronger Norma Edith López-Diazguerrero et al 2013 
7. Ageing Res Rev. Hormesis and epigenetics: is there a link? Alexander M Vaiserman et al. 2011
8. New hallmarks of ageing: a 2022 Copenhagen ageing meeting summary Tomas Schmauck-Medina - Aging
9. Hormesis in aging. Ageing Res Rev. Rattan SI. 2008 
   

Using the right amount of a skin care product is as important as picking the right product(s). If you don't apply enough of the product or for a too short duration, you will not get the optimal result. This is particularly crucial when using sunscreen to reach the sufficient SPF level and protection. According to a study published in the Journal of the American Academy of Dermatology by Andreas Storm MD et al. 95% of patients with a topical treatment under-dose, hence do not use enough cream.

​If there is a specific user manual mentioning the dosage, or you got a prescription, follow their recommended instructions. If the product came without specific dosage instructions, there is a general rule of thumb. The recommended amount of product to apply varies, depending on the product type.

THE 2 FINGERS RULE FOR SUNSCREEN
For sunscreen you need 1/2 teaspoon for the face or enough to cover the bottom of a shot glass and a full shot glass for the body, which should add up to 2mg per cm2. Another method is using the "rule of nines, which is used for burns. The body areas are divided into 11 area's, each representing 9% of the total. Sunscreen can be applied to each of these areas at a dose of 2 mg/cm2 (regardless phototype) if two strips of sunscreen are squeezed out on to both the index and middle fingers from the palmar crease to the fingertips, thus 2 fingers. (1)
The body areas are:
1 Head, neck, and face
2 Left arm
3 Right arm
4 Upper back
5 Lower back
6 Upper front torso
7 Lower front torso
8 Left upper leg and thigh
9 Right upper leg and thigh
10 Left lower leg and foot
11 Right lower leg and foot

FINGERTIP UNITS
For the use of other topical products there is a guidance created called Finger Tip Units or FTU's by CC Long and AY Finlay. It is a way of measuring the amount of product squeezed out of a tube with a 5mm diameter nozzle and applied from the distal skin-crease (the crease closed to the fingertip) to the tip of the index finger.

The FTU concept has been used as a central part of an education programme for parents of children with atopic eczema, has been advocated to reduce the variation in usage of topical steroids and to encourage adherence to therapy. For a serum, you may need less as they are lightweight products which should be fully "absorbed" without residue. If the skin still feels sticky after 1 minute, you probably applied too much product. A guidance would be a pea size dot on forehead, right cheek, and left cheek, which is similar to the recommended amount of retinoids (Vitamin A). However, unlike Vitamin A, using too much serum usually isn't harmful for the skin, but increases the risk of "pilling".

The precise number of FTU's required:

• face 1
• front neck and décolletage 1
• back neck 0.5
• face and neck (front and back) 2.5 
• front of trunk 6.7
• back of trunk 6.8 
• arm and forearm 3.3 
• hand 1.2 
• leg and thigh 5.8 
• foot 1.8 
• entire body 40 units

One FTU covers 286 cm2, more specifically in males and 312 cm2 in females 257 cm2. 

The quantity of cream in a fingertip unit varies:
Adult male: 1 fingertip unit provides 0.5 g
Adult female: 1 fingertip unit provides 0.4 g
.
Keep in mind this is a general guideline and the amount of product needed or results may vary also depending on skin type, concerns and the products particular attributes.

​Take care (in the right amount and duration)

​
References:
1. BMJ. 2002 Jun 22; 324(7352): 1526.Simple dosage guide for suncreams will help users Steve Taylor et al.
Illustration Tinea incognito with unjustified use of potent Topical Corticosteroids: a case series July 2017 International Journal of Basic & Clinical Pharmacology 6(8):2087 Haiya Sheth et al.

Something I am asked quite regularly is if low humidity can dry out the skin. The answer is yes it can. However, it really depends on your skin. There are 4 skin types: normal, dry, combination and oily. According to the (AAD American Academy of Dermatology) sensitive skin is a skin type too, however some would say all skin is sensitive and I somewhat agree. Dehydrated skin is not a skin type, but a (temporary) condition. Your skin type is pretty much set for life and not changing with the seasons. There is an exception as normal, oily or combination skin may become dry(er) post-menopause. The environment, including temperatures and humidity impact our skin significantly. 

Humidity
Humidity is the amount of water vapor in the air. If there is a lot of water vapor in the air, the humidity will be high. A relative humidity of 70 percent means the air is at 70 percent of its water-holding capacity for the present temperature. Cold air cannot hold as much water vapor as warm air. Thus, as temperature falls, with no change in the amount of water in the air, the relative humidity rises.

HIGH HUMIDITY
A study showed that in a dry environment the skin hydration decreases but the amount of sebum increases to compensate for skin dryness. (1)
High humidity can be beneficial if you have dry skin, however can cause problems if you have oily or combination skin. Low levels of humidity can negatively affect your skin, even when your skin is oily. In general high humidity levels has some benefits.

Hydration
The increased levels of moisture in the air in high humidity decrease trans-epidermal-water loss of water evaporation from the skin. Hence, your skin is able to maintain it's hydration levels.

Increased cell regeneration
A moisture-rich climate can also promote skin cell turnover and desquamation (the shedding of dead skin cells). Skin’s regeneration process is increased when your skin is well hydrated. The shedding of dead skin cells is the last step in this cell-turnover or regeneration process and good desquamation leads to smoother texture and more radiant skin. 

Well-ageing effects
Fine lines and wrinkles are more noticeable if your skin lacks moisture and feels dry. Moreover, skin regeneration process declines as we age. Since high humidity positively contributes to hydration, lines and wrinkles are less pronounced and the regeneration process supported, therewith leading to more youthful looking skin. 

Increased sebum production
If your skin is oily, high humidity (especially heat thus sweat) can increase sebum production. An overproduction of sebum, especially in combination or oily skin types can make your skin oily and greasy. Moreover, dirt and irritating particles may "stick" better to greasy skin.

Acne prone skin
Excess sebum and oil caused by high humidity (heat and sweat)  increases the risk of clogged pores, break-outs and comedones (blackheads, and whiteheads). 

Heat or sweat rash
Heat rash, or sometimes called prickly heat, sweat rash or miliaria, is a harmless but very itchy or prickling skin rash. It causes small red (raised) spots in places where sweat collects, such as the armpits, back, under the breasts, chest, groin, elbow creases and back of the knees, and the waist. Although uncomfortable, it is usually harmless and improves on its own after a few days.

Tips to take care of your skin in humid conditions

• Wash your face regularly with a gentle cleanser to remove sweat, dirt, and impurities
• Use a toner to re-balance skin's pH level after cleansing
• Use a (light) moisturiser at all times, preferably with SPF
• Apply anti-oxidants. For example a product combining fresh L-Ascorbic Acid and Licochalcone A (excellent for every skin type)
• If you have oily skin, use a care product with oil-control or sebum regulating properties (for example: L-Carnitine) 
• Avoid touching your face
• Exfoliate to encourage the removal of dead skin cells 
• Drink plenty of water
• Wear loose cotton clothes
• Take (short) cool baths or showers
• Use antiperspirant (designed to reducing sweat)
• Don't neglect the skin of your body or lips

LOW HUMIDITY 
Low levels of humidity most commonly negatively affect your skin.

Decrease skin regeneration
When your skin is not well hydrated, the skin's regeneration process including shedding of dead skin cells is impaired. This can lead to a more dull, rough or even flaky skin.

Dehydrated skin
Your skin can get dehydrated or deprived of moisture when exposed to low humidity levels and the skin looks less radiant or glowing.

Sings of ageing
When your skin lacks moisture, the skin is less plump and wrinkles, fine lines become more visible. 

Worsening of skin conditions
If you have eczema or another problematic impaired barrier related skin condition, low humidity can cause flare-ups. It can also cause or worsen dry skin symptoms like redness, scaliness, rough texture, cracks, itchiness, stinging, burning and the skin might  be more prone to irritation and infection.

Tips to care care of your skin in low humidity

• Wash your face with a very gentle (not stripping) cleanser 
• Use a toner to re-balance skins pH level, this supports skin's barrier function
• Apply a lipid rich (or if needed a semi-occlusive - this prevent trans-epidermal water loss) moisturizer
• You can use care products containing hyaluronic acid. If well formulated, they will not decrease (this is a myth) however improve skin's own hydration
• Apply SPF during daytime (always)
• Exfoliate not more than 2 times per week - avoid over-exfoliation  
• Drink plenty of water (always)
• Take (short - never hot) baths or showers
• A humidifier can add moisture to the air and prevent skin dryness. A study showed that to avoid dryness of the eyes and skin, it is necessary to maintain a relative humidity level of > 30% . (2)
• Don't neglect the skin of your body or lips

​Take care

References

1. A study of skin characteristics according to humidity during sleep. Sue Im Jang et al. Skin Res Technol. 2019 Jul;25(4):456-460.
2. Physiological and subjective responses to low relative humidity Yujin Sunwoo et al. J Physiol Anthropol. 2006 Jan.

It is widely known that skin´s own hyaluron is a precious molecule keeping our skin hydrated as it is a powerful humectant (attracting and binding water), hence giving the skin a natural plumpness and bounce. What many don´t know is that skin´s own hyaluronic acid content needs to be replenished continuously, as it´s half-life is only several hours up to one day 1. It´s degradation is fastened by 2 different pathways: an external influence via free radical activity or physical degradation and an internal pathway via enzymatic or biological degradation by a family of enzymes called hyaluronidase or abbreviated HYAL.

There are 6 different ones identified and HYAL 1 is the most active one. HYAL 1 “cuts” large size hyaluron molecules (the most capable of binding water) into smaller molecules, which are eliminated even faster. One of the strategies to maintain skin´s own hyaluron content is to inhibit the HYAL enzymes, especially HYAL1. Comparing photo-exposed skin to photoprotected skin showed significant increase in the expression of L-HA (low molecular weight HA) which are smaller or broken hyaluronic acid molecules. An increase of degradated hyaluron was associated with a significant expression of HYAL-1 (2)..UV, ROS or free radical activity leads to the activation of hyaluronidase (3,4).

You may now wonder how it is possible that hyaluron filler injections can have a lasting effect of several months or even longer than a year. This is because in those injectable gels the hyaluron molecules are stabilized to protect them from the impact of free radicals and HYAL enzymes. Often this is done with chemical crosslinks (BDDE). Manufacturers of those hyaluron injectable gels use different stabilizing or crosslink technologies and different number of crosslinks, which impacts the gels consistency and longevity. They aren´t completely resistant to hyaluronidase, as it can be used to dissolve injected hyaluron. As hyaluron is anyway depleted and replenished every day, this dissolving procedure hardly affects skin´s own hyaluronic acid content. This is a common misconception.

In skin care however, the use of crosslinked hyaluron (hence lasting for months or longer) does not make a lot of sense as we usually cleanse our skin twice daily and thus wash it away. It is too large to penetrate. There are some benefits for crosslinked hyaluron, but it does not impact the longevity of skin´s own hyaluronic acid content. One ingredient derived from the roots of Chinese Licorice plant called Enoxolone (also known as Glycyrrhetinic acid) however, has proven to decrease the HYAL1 activity by 54% (in vitro) (5.6). This is a novel and safe topical way to protect skin´s own hyaluronic acid content from fast degradation and elimination.
​
However, as mentioned before free radicals increase HYAL1 activity and as we age our skin becomes less resilient against accumulated oxidative stress. Therefore, the most optimal approach to inhibit increasing break down of hyaluronic acid is to combine HYAL1 inhibition with powerful anti-oxidants. In the illustration, which I created professionally, it is Saponin. Saponin is next to a powerful anti-oxidant, also a potent bio-stimulator of the fibroblast for hyaluron (+256%), collagen (+49%) (6) and elastin (+19%). Furthermore, Enoxolone stimulates melanin production, supports the skin's own repair mechanism against UV-induced DNA damage and inhibits enzymatic elastin degradation. What a power-couple to have in dermo-cosmetic products to manage the biological degenerative process of ageing skin. 
 
Take care

1. HA: a key molecule in skin aging E. Papakonstantinou
2. Dermatoendocrinol. 2012 Jul 1; 4(3): 253–258. doi: 10.4161/derm.21923 Hyaluronic acid: A key molecule in skin aging Eleni Papakonstantinou, 1 Michael Roth, 2 and George Karakiulakis 1 
3. BMC Complementary and Alternative Medicine December 2013, 13:304| In vitro determination of the anti-aging potential of four southern African medicinal plants Authors Gugulethu NdlovuEmail, Gerda Fouche, Malefa Tselanyane, Werner Cordier, Vanessa Steenkamp
4. Bioorg Chem. 2018 Apr;77:159-167. doi: 10.1016/j.bioorg.2017.12.030. Epub 2018 Jan 4. In-vitro evaluation of antioxidant, anti-elastase, anti-collagenase, anti-hyaluronidase activities of safranal and determination of its sun protection factor in skin photoaging. Madan K1, Nanda S2.
5. EADV Poster 2021 A holistic hyaluron-centric anti-aging concept to improve static and dynamic wrinkles Geloven van A, Harbig S, Stuhr A, Dunckel J, Kuhn A, Dippe R, Warnke K, Beiersdorf AG, Hamburg, Germany 
6. EADV Poster 2021 Multifaceted novel approach to increase skin’s own epidermal & dermal hyaluron content Bussmann T, Warnke K, Krüger A, Möller N, Harbig S, Stuhr A, Dunckel J, Geloven van A, Weise J, Beiersdorf AG, Hamburg, Germany
7. Hong et al. Glycyrrhetinic Acid: A Novel Modulator of Human Skin Pigmentation and DNA-Repair September 2009Journal of Investigative Dermatology Conference: 39th Annual European-Society-for-Dermatological-Research Volume: 129

Reading the instructions on cleansing and care products can be misleading. When do I pat my skin dry first or when do I apply the product on damp skin? Even many recommendations from skin care guru's or skinfluencers are not completely correct. 

In general it is recommended to apply a serum, eye care or moisturising / hydrating care product on damp skin, or immediately after bathing for the following reasons:

Increased Absorption
The primary benefit of applying skin care products to damp skin is that the skin is more receptive to the ingredients. Water helps to increase the hydration levels of the skin cells, which then improves the absorption of the skincare products. When the skin is damp, the skin's surface is more permeable, allowing the ingredients in the skin care products to penetrate deeper into the skin, and work their magic. Absorbing the ingredients more effectively, this leads to better results.
The exception are products which require a very low pH level to penetrate, and be more effective, for example L-Ascorbic Acid (Vitamin C) and chemical exfoliating "acids" like hydroxy acids. The reason is that water has a pH level of 7-8, acidic formulations will be "neutralised" on damp skin.

Better hydration
Applying skin care products to damp skin helps to lock in moisture, leaving your skin feeling soft, supple, and hydrated. Hydration is critical for the skin because it helps to maintain and restore the skin's barrier function. The skin barrier protects the skin from losing hydration and prevents irritants and bacteria from entering. Applying serums and moisturisers on damp skin, increases the hydration benefits from the products.

Improved spreadability
Another advantage of applying skincare on damp skin is that it helps to improve the spreadability of the product. When we apply products such as serum or moisturiser to dry skin, they tend to settle in one area and can be challenging to spread evenly. On the other hand, when applied to damp skin, the skin care products can spread easily and evenly across the skin surface, ensuring maximum coverage and benefit.
The exception are lipid rich products which are hydrophobe (water repelling), for example ointments, they might not spread evenly or easy on damp skin.

Enhanced performance
Applying skin care products to damp skin has been shown to improve their performance. This is because when products are applied to damp skin, they are less likely to evaporate, and the ingredients remain active for longer. This increased contact time with the skin leads to better, more effective results.
The exception are products containing vitamin A, retinoids, tretinoin, retinal, retinol, retinaldehyde as damp skin increases the risk of irritation.

Sensitive and hyper-sensitive skin
Usually people with sensitive and hyper-sensitive skin have an impaired skin barrier function, hence ingredients will penetrate better in comparison to a resilient and well-functioning skin barrier. Applying products on (hyper)sensitive skin will therefore increase the risk of irritations. Be mindful which ingredients you use and use a pH rebalancing toner after cleansing and prior to any serum or care product you use. A toner is anyway an affordable product, which I highly recommend to use in every skin care routine. Read more.

Study results on patients with dry skin and healthy volunteers
In healthy subjects, compared to at control sites, the Stratum Corneum Water Content (SCW) was significantly higher at sites treated with the moisturizer immediately after bathing, with 1.0 and 2.0 mg/cm2 of the moisturizer, and with once- and twice-daily applications.
In patients with dry skin, the SCW was significantly higher compared to control sites after 8 weeks when the moisturizer was applied twice daily. Read more.

Take care.

Skip-care is a skincare trend that has taken the beauty world by storm for a while now. It is a Korean beauty inspired technique that focuses on simplifying your skin care routine by skipping steps and using multi-purpose products. This skin minimalistic approach will save time, money and reduces the risk of skin irritation caused by the overuse of certain products or combinations.

Skip-care is rooted in the Korean beauty philosophy of ‘less is more’. The skincare industry in South Korea is one of the most innovative and advanced in the world, and they have been leading the way when it comes to skincare trends. The Korean beauty industry is famous for their 10-step skincare routine, which is aimed at improving overall skin health and beauty. However, this long and high-maintenance routine is not for everyone, and this is where skip-care comes in as an alternative approach. It aims to simplify the routine and accessible to people who do not have the time or resources to devote to a lengthy skincare routine.

Skip-care steps:

1. Cleanse: Start by cleansing your skin to remove any dirt, oil, or makeup from your face.
2. Tone: Use a hydrating toner that both re-balances the pH of your skin and preps the skin for the following steps. (There is an all-in-one toning cleanser)
3. Treat: Apply a serum that targets specific skin concerns that you might have (for example hyaluronic acid serum for hydration and wrinkle reduction)
4. Care + Protect: Use a moisturising care product (day care with SPF + anti-oxidants) enriched with ingredients that your skin needs

If you want to go very minimal, you could combine cleanse and tone by using an all-in-one toning cleanser, skip the "treat" step and your skip-care routine is reduced to 2 steps only.

Con's:

1. Not recommended if you have specific skin concerns that require more attention and specific treatments.
2. May not provide the same level of visible results as a full skincare routine.

A benefit on top of saving time, money and reducing the risk of irritation is that by simplifying and streamlining your routine, you probably increase compliance. The best skin care routine is still the one you actually adhere to. 

Take care

It was always believed that the moment we are born, is the moment we are exposed to environmental influences. The truth is that there is ample evidence that already during pregnancy the mothers behaviour: smoking or food has a significant impact on how well we age. We know that all skin needs to be protected against UV and HEVIS by using sunscreen, especially in sun exposed areas from birth onwards.

Although you can not start too early taking care of your skin, the right age to start with a well-ageing skin care routine is actually just post-adolescence for 3 reasons.

1. During adolescence most start with their first cleansing and care routines to remove access of sebum, debris and reduce plus prevent break-outs or comedones. Boys may already shave facial hair. So teenagers or young adults are used to a morning- and evening skin care routine which benefits the overall sense of well-being.
2. Most commonly growth stops when puberty ends and this is the moment the degenerative biological process starts, even though there are no visible signs yet.
3. Prevention of pre-mature ageing skin is the most effective and efficient strategy. 

SKIN NEEDS CARE
There is a movement stating that normal unproblematic skin doesn't need care. I strongly disagree. The choice of products at this age depends of course on the skin type, skin condition, skin health, and environment (like weather conditions, pollution), however the morning care should always focus on protecting every skin type, using suncreen (UV + HEVIS protection) and ideally complimented by anti-oxidants to reduce damaging free radical activity, while the evening routine should at least include proper cleansing (to remove dirt and pollutants), which may be followed by product catering to specific needs, like for example sebum regulating, barrier repairing or hydrating ingredients. I would not make a differentiation between darker or lighter skin in terms of photoprotection, as dark skin only has a natural SPF of 13.3 and light skin of 3.4, hence both not enough to prevent sun damage. However, dark skin has a lower amount of ceramides in the statum corneum and is therefore more prone to trans-epidermal water loss. 

LAZY SKIN?
If you are afraid of spoiling your skin and making it "lazy" using skin care for a long time, know that all effects from a dermo-cosmetic product are 100% reversible, thus temporary. This is regulated by law and to enjoy the benefits from skin care, you need to keep using the products. When you stop, your skin will bounce back to it's original state at least after a full regeneration cycle of about 28 days. A few things to avoid are: sun-damage, especially burns, over-exfoliation (damaged skin barrier) and slugging of oily or acne-prone skin (breakouts). 

Take care.

Mood-boosting skin care can be defined as a skin care routine that includes products and/or tools and techniques which (may be specifically designed) enhance our mood and mental well-being in addition to improving the overall health and appearance of the skin.

Research has shown that skin care is becoming more than just a physical experience, but also a therapeutic and emotional one. The role of mood-boosting skin care in providing self-care and supporting mental well-being has become increasingly important and has profound benefits.

ESSENTIAL OILS
These mood boosting routines typically incorporate products that have essential oils that help to relax, uplift, and calm the mind, which in turn, affects an individual's mood positively. However, I am not a big fan of incorporating essential oils in a skin care routine as they can be irritating, cause skin sensitivity, redness and breakouts. Irritation and redness can be signs of sub-clinical inflammation and speed up the biological degenerative process called skin ageing or skin inflammageing. It is not a surprise that dermatologists warn against the use of most essential oils on the skin. When it comes to essential oils, it is best to use them in a diffuser and not skin care. Facial oils can be beneficial however in a skin care routine. Click here to read more about the use of facial oils.

A SPA "ME" MOMENT
The ancient Greeks were the first to suggest that spas and bathing could be used for therapeutic purposes and not just for hygiene and cleanliness (which are basic requirements for good skin health). A warm relaxing bath isn't always good for skin health however (1). On the other side a 20-30 second cold shower after a workout or sauna encourages the release of cold shock proteins. Cold shock proteins may help you maintain your muscle mass when you're too busy to make it to the gym or when you're taking some planned time off your training routine. Some cold shock proteins are known to decrease inflammation and support faster wound healing. Cold water immersion also activates brown fat, tissue that helps keep the body warm and helps it control blood sugar and insulin levels. It helps the body to burn calories, hence to lose weight. Click here to read more.

A SPA BONDING MOMENT
As time is precious, meaningful time together with friends, your partner or your kids, can boost your sense of satisfaction and strengthen bonds. Funny anecdote was that I was "masking" with my son, who was at the time 12 years old. While relaxing he asked me what his mask was actually doing and I told him that it makes you look younger. He immediately asked me to remove it, scared he would look afterwards like 7 years old. 

JADE ROLLERS & GUA SHA
I love using (refrigerated) jade rollers and gua sha, especially in the under eye area in the morning to reduce puffiness, increase the circulation and lymph drainage. It is important that the tools glide over the skin, don't tug and thus I apply a nourishing care product first. Moreover, applying skin care products using mindful techniques such as massaging in gentle circular motions can be therapeutic, providing a sense of calm and relaxation.

SKIN CARE ROUTINES
Mindful evening skin care routines have been shown to be particularly beneficial in unwinding after an overwhelming day, helping to reduce stress and induce better sleep. As it turns out, consistent routines provide more stability in your day, which is beneficial for your mental health and stress level regulation. Therewith every morning- and evening skin care routine is mood-boosting.

DO GOOD, FEEL BETTER
If you treat your self and your skin good, it will make your skin look better and even improve your quality of life. Self-care enhances feelings of self-worth, boost self-esteem and can even give a sense of accomplishment, is thus mood boosting, even without the use of aroma therapy or essential oils. 

Take care

We all learned that sleeping in make-up is the ultimate skincare sin. What is bad about it is when you go 24 hours without washing your face and end up going to bed leaving your day-time make-up on. Over the course of the day, our skin accumulates pollutants, dirt and dead skin-cells.

If dirt and pollutants are left on the skin, they may cause micro-inflammation and contribute to premature ageing skin via a process called inflamm-aging and free-radical damage which is a major contributor to skin-ageing. The combination of both micro-inflammation and free-radical damage is called ox-inflammation. We should aim to reduce or preferably avoid it. Pollution, dirt and sebum (oils) can impact the skin's healthy pH balance and thus lead to a weakening of the skin barrier function, more sensitive skin, dehydration, slowed down skin-cell renewal process and thus ageing. Not removing dead skin cells together with dirt increases the risk of clogged pores. 

Make-up itself usually doesn’t contain harming ingredients. Coloured micro-pigments actually provide additional sun-protection. Make-up or foundation itself is thus not the problem, however the fact that we don’t cleanse our skin after a busy day and/or evening is what could make us age faster. Not doing your PM cleanse and care routine is anyway a missed opportunity to support your skin’s night-time recovery with beneficial active ingredients.

If you go out in the evening, take the opportunity to cleanse before getting ready and get rid of debris which was accumulated during day-time.

Don’t worry about falling asleep in your make-up once or twice. Just don’t make it a habit. I would always aim to remove eye make-up. Sleeping in full eye make-up (mascara, liner, eyeshadow) increases the risk of an eye-inflammation, redness and corneal abrasions. Waking up with “panda-eyes” filled with black rheum or goop isn’t pretty either.

Take care

Our life expectance is increasing and the average age when menopause occurs didn't change much in the last decade. This is why more women will have to care for post menopause skin for a longer time. During and after menopause our skin will go through some changes and might even become problematic. In this blog post I will have a closer look into these changes.

Change
During the start of menopause, also called peri-menopause, women will notice some changes to their skin. This is because estrogen levels start to decline (-35% between age 35-50) and as estrogen level decline, androgen level proportionately become more dominant. As a result, the majority of women experience drier skin. Or when the hormone levels are differently balanced they may get a more oily skin or develop acne tarda (adult acne), because the oil gland activity is increased. Another problem is that the skin's pH level will increase, which will impact skin health, barrier and microflora or microbiome. A higher pH value may result in problematic skin.

Loss of biological activity 
Around this period the metabolic biological activity in the skin will decrease faster than in our 20s or 30s. The production of important components like hyaluronic acid (filling + hydration), collagen (strength + structure) and elastin (flexibility + stretch) by fibroblasts (a very important skin cell) isn't sufficient, while the speed of their degradation is inclining because the skin's natural resilience against damaging free radical activity is reduced and the activity of degradation enzymes, like hyaluronidase, collagenase and elastase is elevated. Therewith the presence of those important skin components is declining 30% in the first years. This leads to more advanced signs of ageing skin and an overall loss of skin quality: skin firmness, skin surface eveness, skin tone eveness and glow (Goldie, Clin Cosmet Invest Dermatol, 2021). 

Solution
Skin ageing is a multifaceted continuous biological degenerative process, with an impact on overall skin quality, self perceived attractiveness, confidence and comfort (Quality of Life). The optimal solution should improve all 4 emergent perceptual categories or EPG's of skin quality (an important component of human attractiveness) as mentioned above. This can be achieved by supporting skin's own resilience against the inclined loss by degradation (reduce free radical and enzymatic activity) and increase skin's own biological activity, hence skin's own production of hyaluron, collagen and elastin with bio-active ingredients or bio-stimulators and inhibit human tyrosinase activity (reduce age spots). I will explain the 4 key actions below:

1. Bio-stimulators
Some evidence based bio-actives we can find in skincare are:

• 52 kDa Micro-Hyaluron (stimulation of hyaluron production with 209%: hyaluron-filler)
• Creatine (stimulation of collagen I and IV by + 35%  and elastin with +36%)
• Glycine Saponin (stimulation of hyaluron production +256% collagen +49% elastin +19%) which is also a powerful anti-oxidant

There are very good in-office treatments for bio-stimulation.

2. Enzyme inhibitors
Some ingredients in skincare which inhibit enzymatic degradation are:

• Enoxolone (reduces hyaluronidase I activity by >50%)
• Arctiin (reduces HN-elastase activity by 79%) and is also an anti-oxidant

3. Anti-oxidants
Damaging free radical activity is increased in mature skin and ROS (Radical Oxidative Species) increase degradation of all components, enzymatic degradation and human tyrosinase activity, a powerful cocktail of anti-oxidants is a "must-have". The combination of fresh activated L-Ascorbic-Acid (primary defence with instant neutralisation of extra-cellular free radicals) and Licochalcone A (secondary defence with long-lasting intracellular stress protection is a valuable addition in any day or nighttime skincare regimen. Licochalcone A is moreover one of the most powerful anti-oxidants (if not the most powerful one) proven to reduce (deep) oxidative stress from High Energy Visible Light or HEVIS. As we know, free radicals from HEVIS damage the important skin-cell called the fibroblast and increase the risk of age spots. 

4. Human tyrosinase inhibition
A relatively new, effective and safe ingredient in skincare which was tested on inhibiting human tyrosinase is Thiamidol. Other ingredients in skincare were tested on mushrooms (Hornyak, Journal of Investigative Dermatology 2018 & Mann et al. 2018) and are not potent in reducing human tyrosinase activity. It took 10 years of pioneering research (dr Ludger Kolbe) and comparing 50.000 actives to patent and market it. In the mean time Thiamidol is loved and recommended globally by many dermatologists and evidence based with 35+ studies including >2000 participants with all Fitzpatrick phototypes. 

Every AM routine should at least have a skincare product with SPF of 15 or higher.
An improvement of skin quality leads to an improvement of quality of life (van Geloven et al. EADV 2022). 
​
Hope this was helpful.
Take care

Vitamin C is a "must have" skin care ingredient our skin needs at any age.
 
One of the best researched skin care ingredients and proven to be very beneficial for skin is Vitamin C. Our skin uses Vitamin C as an anti-oxidant and the dermal fibroblasts need Vitamin C for the production of collagen. Two very good reasons to add this ingredients into your daily skincare routine whether you are twenty or eighty. Moreover, our skin depends on us for the needed supply, as our skin is not able to produce Vitamin C itself.
 
We can either include enough Vitamin C in our diet or apply Vitamin C topically there where we need it the most. Usually this is the skin which is exposed to (sunlight) as this increases damaging free radical activity in our skin. An active form of vitamin C can reduce the free radical activity, which we call anti-oxidative effect. 
 
There are 4 things to consider when buying a skincare product containing Vitamin C:

1. Vitamin C needs to be used in an active form. Fresh reconstituted (mixed) L-Ascorbic Acid is the most active form of Vitamin C. A stabilized form of Vitamin C is not active anymore and therewith not as effective or not effective at all.
2. The formula has to have a low or very low pH value in order for the vitamin C to penetrate well into the skin.
3. The percentage of vitamin C needs to be above 8 and not over 20 to be optimal. For a good balance between great efficacy and tolerability, 10% fresh L-Ascorbic Acid is just right. Higher might not add much efficacy, but could create tolerability issues, especially for more sensitive skin.
4. The packaging and application form should protect the formula from light & air as much as possible. A dropper for example will expose the formula to air with every use.

 
Day or night?
Some recommend to use Vitamin C during the night, as the active form of Vitamin C will oxidize in daylight. Hence, your skin can benefit from the Vitamin C longer during the night. I would recommend Vitamin C to be used during daytime (thus added to your morning routine), as we need protection from damaging free radicals the most during daytime and the oxidization of Vitamin C is actually a sign that the ingredient is doing it’s job! It’s even better to add Vitamin C both to your day & night time skincare routine.
 
Is L-Ascorbid Acid enough?
Vitamin C is counteracting free radicals from UV light. However, UV is not the only damaging light form as there is also High Energy Visible Light or abbreviated HEVIS. This penetrates even deeper into the skin where also the dermal fibroblasts reside. The dermal fibroblasts are our collagen and hyaluronic acid producing cells and a key target in an effective anti-ageing skincare strategy. Lichochalcone A (Licorice-root extract) has proven to be the most potent anti-oxidant to protect the dermal fibroblasts and neutralize free radicals from HEVIS. Moreover, Lichocalcone A increases Glutathione, which is a skin’s own anti-oxidant. Licorice-root extract is an anti-ageing hero.

Summary
The combination of Vitamin C and Lichocalcone A will protect our skin and dermal fibroblasts from free radical damage by UV and HEVIS and will provide superior biological cell protection in comparison to Vitamin C only. For me this is a good reason to use a product containing both ingredients as a first step after my cleansing routine in the morning. If you have sensitive eyes, I recommend to use an eye care prior, which will form a barrier to help to prevent the low pH Vitamin C product to migrate into the eye area. Afterwards you can use the other products of your skincare routine. I would like to put emphasis on using a SPF of 30 or higher during the day. This will not only help to protect your skin, but also support the anti-oxidative benefits and make them last longer.
 
Hope this was helpful.
Take care!

One of the frequently asked questions is, if it's necessary or if there is a benefit using a special eye care or cleansing products. Yes, there is!

As I mention in many of my previous posts, the right pH-level is very important for healthy skin. Skin usually prefers a pH of around 5. However there are some area's where the skin's natural pH balance is a little bit different. One of those area's is the area around the eyes. The preferred pH-level there is around 7, thus less acidic and more alkalic in comparison to your regular cleansing or care product for face or body.

This is one of the most important reasons why I would recommend to use a special eye make-up remover and eye care product, as they are adjusted to the pH level most suitable for use in the eye area. Furthermore, special eye products are tested and proven to be safe when used around the eyes, while it isn't always recommended or proven for a regular face product. 

Some care products have a tendency to "travel" or migrate into the eye area. Even when not directly applied around the eyes, they might end up there. A special eye care product can form a "barrier" and thus help to prevent that unwanted products move to the eye area and cause irritation. I would particularly recommend the use of an eye cream when using other products containing gold standard anti-ageing active ingredients like Vitamin A, C (or derivatives of both), Hydroxy Acids (Alpha, Beta or Poly), when you have experienced some sensitivity of the eyes or eye area in the past or have a more problematic skin type.

Eye care products preferably should not contain Vitamin C (L-Asorbic Acid or related) as it requires a low pH value of <4 to be active and do it's job properly. Eye care products with Vitamin C therewith are either too acidic to be used in the eye area or alternatively too alkalic for the Vitamin C to be effective. Safe to use in the eye area are products containing Hyaluronic Acid. Although  "Acid" is in the name, Hyaluronic Acid isn't acidic. One of it's key functions is attract and bind water, which usually has a pH of ~7.

Take care!

Safe use of cosmetics and care products is particularly important for the sensitive eye area. If you've ever or never had a problem, here is how you can avoid them.. 

Irritation
If any eye cosmetic or care product causes irritation, stop using it immediately. If irritation persists, see a health care provider.

Infection
Avoid using eye cosmetics if you have an eye infection or the skin around the eye is inflamed. Wait until the area is healed. Discard any eye cosmetics you were using when you got the infection. Be aware that there are bacteria on your hands that, if placed in the eye, could cause infections. 

Hygiene
Wash your hands before applying eye cosmetics. Make sure that any instrument you place in the eye area is clean. Don't share your cosmetics. Another person's microflora may be hazardous for you.

Packaging
Don't allow cosmetics to become covered with dust or contaminated with dirt or soil. Keep containers and nozzles clean. Don't use old containers or eye cosmetics and don't re-use containers. Never trust a product that smells funky, looks dirty, or past the open-jar time.

Mascara
Discard dried-up mascara. Don't add saliva or water to moisten it. The bacteria from your mouth may grow in the mascara and cause infection. Adding water may introduce bacteria and will dilute the preservative that is intended to protect against microbial growth. Manufacturers usually recommend discarding mascara two to four months after purchase.

Storage
Don't store cosmetics at temperatures above 85 degrees F or 30 degrees Celsius. Cosmetics held for long periods in hot cars, for example, are more susceptible to deterioration and bacteria. Some products are best stored in the refrigerator. Read the leaflet or follow the instructions how to best store the product.

Application
When applying or removing eye cosmetics, be careful not to scratch the eyeball or other sensitive area. Never apply or remove eye cosmetics in a moving vehicle. Don't use any cosmetics near your eyes unless they are intended specifically for that use. For instance, don't use a lip liner as an eye liner. You may be exposing your eyes to contamination from your mouth, or to color additives that are not approved for use in the area of the eye. Avoid color additives that are not approved for use in the area of the eye, such as "permanent" eyelash tints and kohl. 

Tools
​If you use make-up brushes or sponges, clean them every week with a special product or soap. Give them additionally from time to time an extra spritz with a disinfectant.

Don't mix it up
Sometimes you might feel to mix several products or add something to the product. Problems can arise if you challenge a product’s preservative capability, which is optimal and tested only with the original formula and packaging.

Check ingredient list
As with any cosmetic product sold to consumers, eye cosmetics are required to have an ingredient declaration on the label. Check if there is anything listed you don't tolerate or like. If the product doesn't have the ingredients listed, the product may be considered misbranded and illegal. Do the same for adhesives used for lash extensions or false lashes.

Be aware of testers
Keep in mind when you come across “testers” at retail stores that they might be contaminated. If you do sample cosmetics at a store, be sure to use single-use applicators, such as clean cotton swabs. Check how the store maintains their testers. If possible, ask for a sample, especially for care products. Using a few applications gives you a better idea about the compatibility (how well your skin tolerates the product), if you like the texture and enjoy the product. 

​Take care.

We can support's skin natural exfoliation process in various ways, for example with mechanical or chemical exfoliation. 

Desquamation (shedding of skin cells thus exfoliation) is an important part of the skin's natural regeneration or renewal process.

Already in our twenties, this process slightly, however increasingly starts to slow down (Kligman 1983). As a result, the cells on the surface of our skin (corneocytes) become bigger (Kligman 1989) and a little disorganised. This leads to a duller appearance (loss of radiance) and a more rough texture of our skin.

A very comprehensive comparison of both methods:

The word "acid" unfortunately sounds very harsh and skin-unfriendly. Many acids are actually skin's own, like for example lactic acid is a skin's own natural moisturising factor (NMF) and so is hyaluronic acid. The level of NMF's decrease as we age and our skin my lose the ability to maintain well hydrated. Many years ago the benefits of lactic acid were capitalised by using baths filled with donkey milk. Citric acid is commonly used in skin care products and toners to balance skin's pH. Gluconolactone is only gradually penetrates skin and is very gentle. 

It's unfortunate that "acids" have such a negative connotation, as our skin (healthy and problematic) can benefit if we use them regularly. Moreover, I prefer this method over mechanical exfoliation for all skin types, however particularly if you have dry skin, acne- or redness prone skin, sensitive skin or mature skin. 

The risk of exfoliation is over-exfoliation. Over-exfoliation is damage of our skin barrier and the symptoms are very comparable to dry or (hyper) sensitive skin symptoms, which are: redness, irritation, tightness, excessive dryness, dry patches, flaking skin, uncomfortable stinging, or even burning sensation. Whenever you experience one or more symptoms of over-exfoliation, it's recommended to reduce the number of times you exfoliate and support the skin barrier repair with a moisturiser.

Hope you enjoy healthy skin & take care.

Facial oils are a trending skin care product at the moment, loved and recommended by many "beauty guru's" and skin care experts. This is why I found it very interesting to read a comment written by a well respected dermatologist claiming that face oils would stifle skin renewal and exfoliation and would make skin dull over time. She must have a reason why she is saying this, and that's why I looked into this a little bit deeper.

To start with, I've done own research (not just me) with a facial oil, included many testers and found many benefits and no draw backs during the duration of the study. Moreover, I jumped out of my chair (literally) when I saw the visible results from the clinical photography, no joke! We've found that the oil (a combination of Argan oil and Lady's Thistle oil) improves moisture, elasticity and firmness, supports skin resilience, making the skin feel smooth and look more radiant. There was even a reduction of comedones detected. The results were published in a poster, accepted by the European Academy of Dermatology and Venereology in 2016.

If you are an impatient person, and demand a fast answer, I can spill the tea right now: I've found no data to support that facial oils would stifle skin renewal and exfoliation, but the opposite.

Moisturisers absolutely influence the skin barrier function and TEWL (transepidermal water loss - which is used to measure the skin barrier function). A good barrier function (confirmed by low TEWL), positively contributes to the skin cell renewal process, which includes skin exfoliation process. Very dry skin has an increased TEWL, and so does very well hydrated skin. There is simply more water on the skin surface to evaporate. A high TEWL with very well hydrated skin can therefore give the impression of an impaired barrier function and thus give a "false positive". This phenomenon is nicely explained in a publication by Marie Loden "Effect of moisturizers on epidermal barrier function".

Looking at non fragrance plant oils also called fixed oils, there are many and they are all different, so it's impossible to generalise. Many plant oils, like almond, jojoba, soybean and avocado oils mostly remain on the skin surface. Even without penetrating deeper into the outer layer of the skin (called epidermis), the occlusive effect of plant oils will reduce water evaporation from the skin and help the growth of the cells of the top layer called keratinocytes. They actually support the skin barrier and therewith skin cell renewal. Part of the skin cell renewal is a process called desquamation, which is skin's natural exfoliation of dead skin cells. Helping this process will make skin appear more radiant and smooth, not duller.

​The benefits of plant oils are supported in many publications, one of which is found in the International Journal of Molecular Sciences anti inflammatory skin barrier repair effects by Tzu-Kai Lin 2017. 

Argan oil
One of the most popular and well researched fixed oils is organ oil. It contains oleic and linoleic fatty acids. Both are part of our skin's natural intercellular lipid-enriched matrix or skin barrier. Linoleic acid (an omega 6 fatty acid) is in fact the most abundant polyunsaturated fatty acid. Our skin barrier is protecting our skin from water loss and penetration of external agressors. Thus the skin barrier keeps the good stuff in and bad stuff out.
Linoleic acid plays a direct role in maintaining the integrity of this skin barrier. Some research shows that oleic acid may indeed disrupt the skin barrier and act as an permeability enhancer, helping other ingredients to penetrate deeper. When oleic acid is continuously applied, it could lead to barrier problems. Another ingredient in argan oil is tocopherol or vitamin E.  Tocopherol is well known for it's antioxidative effect (neutralising damaging free radicals from pollution or sun which cause premature ageing) and lesser known for supporting the skin barrier. Daily topical application of argan oil (the finished product which contains multiple ingredients) has shown to improve skin elasticity (firmness), improve the skin hydration by restoring the barrier function and maintaining water-holding capacity. Furthermore it has a softening and relaxing effect on skin. 

Lady's Thistle oil
The oil of the Milk Thistle plant (also known as Silybum Marianium) is a common ingredient in anti-aging skincare. It contains skin barrier supporting Linoleic acid and is known to nourish skin and improve radiance. 

Facial oils are certainly not for everybody, but in general skin will benefit from a cold pressed fixed plant oil or a mixture. Don't smother skin with oils, just apply a few drops by itself on the skin prior or after your moisturiser, or mix a few drops with your moisturiser of foundation. 

Hope you enjoy radiant skin & take care.

Anything you don't enjoy using or doesn't cater to your needs, is not worth buying. 

Skin care is personal and there is a good product for all wallet sizes. However, is a luxury product better than a more affordable one? Is expensive the best?

There are actually many factors influencing the prize of a product, other than the prestigious brand-name and advertising costs.

Note: This content will mainly apply to skin care catering to the need of healthy, thus not problematic skin types. Problematic (or diseased) skin needs special care which usually is not found in the prestige or luxury skin care segment. 

Realistic expectations
If you are disappointed by the results your skin care products, you might not have bought the right product for you. Make sure that your understand your skin type. There is also a change that you might have too high expectations of what skin care can actually do for you. Your skin will definitely benefit from a good skin care regimen with the right product(s). However, don't expect a metamorphosis, especially not from one day to the next. There are limitations to what skin care can do for your skin and actually what skin care is allowed to do. These rules apply for all skin care products.

Formula
Some very excellent skin care ingredients are expensive, however there are many very good ingredients which are affordable. Expensive ingredients can be useless "actives" in skin care, and "sound" appealing. Usually "rare" ingredients are expensive, but not all rare ingredients are "the best" actives. The majority of active ingredients only give visible or noticeable results in optimal concentrations. Many skin care products in the prestige or luxury skin care category have long INCI lists (ingredient lists). This will increase the price of the product, but does not necessarily mean that this is the right skin care for you. Furthermore, there is more to a formula than an ingredient list! If the end products texture (also called galenics) is too greasy or too light for your liking, you might not enjoy using the product, and it is not worth the splurge. Luxury brands invest in pleasurable textures of the formula to ensure a positive user experience and high repurchasing rate. A nice texture, doesn't necessarily ensure high performance of a product. Actually the more occlusive products (sometimes regarded as greasy or heavy), are commonly well performing in preventing transepidermal water loss, thus hydration.

Note: especially with very long ingredient lists it is highly recommended to try the product before you buy, particularly if you have sensitive skin, as the risk of a skin reaction is increased when the number of ingredients is high. Check also if the product was tested and proven suitable for sensitive skin in this case.

Innovation & technology
New active ingredients may be exclusively developed by a company and it took them a lot of time, effort and money to collect enough data and proof that this particular active ingredient is effective and safe to use. Products containing such a (probably patented) ingredient can be more expensive than products with more generic frequently used ingredients. Sometimes expensive technology is especially developed or used to improve the formula, texture or container. 

Packaging
Formula's may need a special container or dispenser to be stored appropriately. This is more expensive than a simple standard packaging. Some containers are only luxury and aim to look amazing in your bathroom or on your dresser. Others might be very "inviting", quick and easy to use. If this is what you prefer and enjoy, it might be worth the splurge.
 
Evidence based
Evidence is in my opinion compulsory, however not always scientific. Real proof and particularly scientific proof or clinical proof is expensive and time consuming. The best proof is a combination of scientific publications (in peer reviewed journals) and "product-in-use" tests (most similar to daily use) with large representative groups. A claim xx% of testers agree with a panel of 6 or 25 testers, is not enough to be significant. If you want certainty about the benefits of a product, a formula which has proven to be very effective and well tolerated might be worth the splurge.

​Usually (not always) brands that are recommended by or sold through dermatologists, aesthetic doctors or health care providers have conducted more rigorous research to provide the doctors with evidence, so they feel confident in recommending the product. 

Likeability brand
Some brands have a great story, background, founder and thus a high likeability or appeal. Some huge companies producing large quantities may have lower production costs per product than small companies producing a limited number of products at an external supplier. Some brands "harvest" their own ingredients, have an intense auditing procedure for suppliers or special requirements for the ingredients they use. These factors influence the price of the product. It's certainly not worth the splurge, if you don't like the brand or the company behind the brand. If you have special wishes or requirements, you might be willing to pay for those. 

Indulge
If you love special skin care, indulging "me-moments" and therewith skin care is high on your priority list, you will look at a pricy skin care purchase very differently from someone who just wants an effective moisturiser. If the product or the purchase makes you more happy and you it's use, it might be very well worth the splurge.

Need
Last but not least, any purchase you make only makes sense if the product fits your needs (skin type and concerns) and your skin care regimen. 

Try before you buy
Some expensive high end products may be worth the splurge, if you enjoy them too. However, there are good affordable alternatives available. The most expensive isn't per se the best or the best for you. Do some research on the product and check reviews from customers. I would recommend to ask a sample and try every product before you buy it and preferably apply it first on the area where you want to use it. For example: applying a product on your hand in the store is not the same as trying it on your face, neck or décolletage! 

I apologise for the length of this blog post, but the answer is not so easy. Any purchase you make depends on what your are looking for, are willing and able to spend. Invest in proper cleansing before applying any serum or care. If the skin care product is so expensive that you are hesitant to actually use it and you know that it will sit in your bathroom untouched, it's not worth to buy it. If you already own such a product, rather use it and keep the empty container on display.

Hope you enjoy and use your skin care. 

Recently I've read an article in which facial toners were called a redundant step in the cleansing routine. They would not serve any purpose anymore and would be “old-fashioned". I disagree, and will explain why.

Particularly when you prefer wet facial cleansing (water has a pH of 7-8), your skin’s pH goes up and you may consider using a toner to bring it back to normal (~5) before using a moisturizer or serum. This also applies if you use an alkaline cleanser or micellar water. It is common that products which are suitable to be used around the eyes, like micellar water, are adapted to a more “eye-friendly” and less “skin friendly” pH of ~7. Skin prefers a pH of ~5.

In my humble opinion, toners are a very important step in every a.m. and p.m. skin care regimen for both healthy and particularly problematic skin  types. They refresh, remove left-over debris and make-up and moreover instantly rebalance skin’s pH value. A balanced pH value is the cornerstone for healthy skin. An optimal pH supports skin's microbiome (microflora or "ecosystem") and barrier function. Furthermore, the use of a toner usually helps the penetration and thus efficacy of your care product!  

Alternatively, you can use “chemical” exfoliating lotions or pads which contain AHA (glycol, citric and lactic acid), BHA (salicylic acid), PHA (gluconotactone), etcetera. Just be careful using them around the eyes or even avoid this area.

Hope you enjoy healthy skin & take care.