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12/7/2024 Comments Collagen banking![]() 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. ![]() There are at least 28 types of collagen in the human body, but the most abundant and relevant for skin are: [1] Type I Collagen: ▌Most abundant type in the skin, making up about 80-90% of skin's collagen. ▌Provides tensile strength and structure to the skin. ▌Maintains skin elasticity and firmness. Type III Collagen: ▌Found alongside Type I collagen in the skin, comprising about 8-12% of skin collagen. ▌Contributes to skin firmness and elasticity. ▌Important in early stages of wound healing and fetal development. Type IV Collagen: ▌Found in the basement membrane of the skin. ▌Provides support and filtration in the basement membranes. ▌Crucial for overall skin health and function. Type V and VI Collagen: ▌Present in smaller amounts in the skin. ▌Support skin health and collagen fibril formation. ![]() 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]. ![]() Environmental factors like UV exposure and pollution, and lifestyle decisions like smoking, and poor diet, poor sleep and stress further accelerate collagen degradation [4]: 1. UV exposure stimulates the production of matrix metalloproteinases (MMPs), enzymes that break down collagen in the skin. 2. Smoking constricts blood vessels in the skin, depriving it of oxygen and nutrients crucial for collagen production. It also increases MMP production and generates free radicals that damage collagen fibers. 3. Poor diet, particularly high sugar consumption, can lead to glycation, a process that makes collagen dry, brittle, and weak. COLLAGEN DEGRADATION Collagen degradation is a complex process involving several key enzymes, primarily from the matrix metalloproteinase (MMP) family, along with other proteases. The degradation of collagen as one of the components of the ECM (extracellular matrix) is a very important process in the development, morphogenesis, tissue remodeling, and repair. ![]() 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.
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 [1] Ricard-Blum, S. (2011). The collagen family. 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Biochemistry, Collagen Synthesis. In StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507709/ [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).
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12/7/2024 Comments The dark side of vitamin C![]() 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. 12/7/2024 Comments Regenerative aesthetics: Wound healing & growth factors for collagen biostimulation![]() Interestingly, the biochemical pathways involved in skin rejuvenation and wound healing share notable similarities. This connection forms the basis for many clinical regenerative aesthetical treatments designed to stimulate collagen production. Interventions, such as chemical peelings and energy-based devices, work by creating controlled damage (wound) to trigger the skin's natural healing response, while topical treatments can include growth factors to boost collagen synthesis (biostimulation) and promote skin regeneration [1]. Wound healing is a complex biological process that relies on the synchronized actions of various cell types, guided by growth factors and cytokines [2]. Central to this regenerative process is collagen, a crucial component of the extracellular matrix (ECM) giving skin strenght and structure, however is declining as we age and therefore a primary target for skin (pre)rejuvenation treatments. Collagen's plays vital roles throughout the wound healing process [3]. The wound healing process has four distinct however overlapping phases (illustration): [3][4] 1. Hemostasis: ▌Platelets release growth factors including PDGF, IGF, TGF-α/β, and EGF, initiating the wound healing cascade and attracting immune cells to the wound site [3][5]. 2. Inflammation: ▌ Growth factors and cytokines released by platelets and immune cells promote inflammation and cellular migration [5]. ▌Macrophages produce additional growth factors, including FGF, which induces fibroblast activation and proliferation [5]. 3. Proliferation: ▌PDGF and TGF-β stimulate fibroblast migration, proliferation, and collagen production [4][5]. ▌FGF promotes fibroblast proliferation and angiogenesis [4]. ▌VEGF is crucial for angiogenesis and the formation of granulation tissue [5][6]. ▌KGF and EGF facilitate reepithelialization by stimulating keratinocyte migration and proliferation [6]. 4. Remodeling: ▌ TGF-β influences the transition from type III to type I collagen, improving wound strength [3][5]. ▌This phase can last from 3 weeks to 2 years post-injury [5]. This explains why biostimulation of collagen production is a gradual process and ultimate results can take weeks or even months. Initially, type III collagen is deposited in the granulation tissue, forming a loose matrix with other components like hyaluronic acid and fibronectin [3][5]. ▌During remodeling, type III collagen is gradually replaced by stronger type I collagen, increasing the mechanical strength of the tissue [3][5]. ▌The collagen fibers are rearranged into a more organized lattice structure, although newly formed scar tissue has only 70-80% of the tensile strength of intact skin [5]. ▌ Fibroblasts and myofibroblasts, stimulated by growth factors, are responsible for collagen production and remodeling [5][7]. Impairments in any phase of wound healing can lead to chronic, non-healing wounds, which is a growing concern in healthcare [3]. ![]() GROWTH FACTORS Growth factors (GF) are naturally occurring polypeptides secreted by various cells including the dermal fibroblast, facilitating signaling pathways between and within cells throughout the healing phases [6]. These factors, including Platelet-Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor-β (TGF-β), among others, function synergistically to guide the wound from injury to complete tissue regeneration [4]. Topical applied growth factors can support this skin rejuvenation healing process [8][9]. However, direct application of growth factors to wounds faces challenges such as rapid degradation in the wound environment and the need for high doses to achieve clinical efficacy [4]. COLLAGEN Collagen, whether in its natural fibrillar form or as soluble parts in the wound environment, closely interacts with these growth factors [3]. Collagen not only provides structural support to the skin, it also actively participates in cell signaling, influencing key processes such as hemostasis, inflammation resolution, angiogenesis, and matrix remodeling [3][10]. The interaction between growth factors and collagen creates a lively environment that is essential for effective wound healing. Some studies suggest potential benefits of oral collagen supplements [11][12][13] and topical collagen products [14] for wound healing. A high quality collagen powder does have right building blocks (amino acids: proline, glycine and hydroxyproline) for collagen production. The effects may vary depending on the type of wound, collagen formulation, and application method. Exosomes [15] Exosomes isolated from stem cell cultures contain various growth factors, including EGF, VEGF, TGF, HGF, FGF, IGF, and PDGF. These growth factors play crucial roles in skin regeneration, anti-aging effects, and wound healing by promoting fibroblast proliferation and collagen synthesis. The use of skin´s own healing power via a regenerative aesthetic treatment causing controlled injury is collagen biostimulatory and the use of topical growth factors, exosomes and oral collagen powders may enhance the outcome. 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] Goldman R. Growth factors and chronic wound healing: past, present, and future. Adv Skin Wound Care. 2004 Jan-Feb;17(1):24-35. doi: 10.1097/00129334-200401000-00012. PMID: 14752324. [2] Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014 Sep-Oct;22(5):569-78. doi: 10.1111/wrr.12205. PMID: 24942811; PMCID: PMC4812574. [3] Mathew-Steiner SS, Roy S, Sen CK. Collagen in Wound Healing. Bioengineering (Basel). 2021 May 11;8(5):63. doi: 10.3390/bioengineering8050063. PMID: 34064689; PMCID: PMC8151502. [4] Vaidyanathan, L. (2021). Growth Factors in Wound Healing – A Review. Biomedical and Pharmacology Journal, 14(3). DOI: https://dx.doi.org/10.13005/bpj/2249 [5] Park JW, Hwang SR, Yoon IS. Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration. Molecules. 2017 Jul 27;22(8):1259. doi: 10.3390/molecules22081259. PMID: 28749427; PMCID: PMC6152378. [6] Barrientos, S., Stojadinovic, O., Golinko, M.S., Brem, H., & Tomic-Canic, M. (2008). Growth factors and cytokines in wound healing. Wound Repair and Regeneration, 16(5), 585–601. [7] Hochstein, A. O., & Bhatia, A. (2014). Collagen: Its Role in Wound Healing. Podiatry Management, 33(6), 103-110. [8] Zarei, F., & Soleimaninejad, M. (2018). Role of growth factors and biomaterials in wound healing. Artificial Cells, Nanomedicine, and Biotechnology, 46(sup1), 906–911. [9] La Monica, F.; Campora, S.; Ghersi, G. Collagen-Based Scaffolds for Chronic Skin Wound Treatment. Gels 2024, 10, 137. https://doi.org/10.3390/gels10020137 [10] Shi, S., Wang, L., Song, C. et al. Recent progresses of collagen dressings for chronic skin wound healing. Collagen & Leather 5, 31 (2023). https://doi.org/10.1186/s42825-023-00136-4 [11] Bagheri Miyab K, Alipoor E, Vaghardoost R, Saberi Isfeedvajani M, Yaseri M, Djafarian K, Hosseinzadeh-Attar MJ. The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial. Burns. 2020 Feb;46(1):156-163. doi: 10.1016/j.burns.2019.02.015. Epub 2019 Dec 16. PMID: 31859087. [12] Choi FD, Sung CT, Juhasz ML, Mesinkovsk NA. Oral Collagen Supplementation: A Systematic Review of Dermatological Applications. J Drugs Dermatol. 2019 Jan 1;18(1):9-16. PMID: 30681787. [13] Katayoun Bagheri Miyab, Elham Alipoor, Reza Vaghardoost, Mohsen Saberi Isfeedvajani, Mehdi Yaseri, Kurosh Djafarian, Mohammad Javad Hosseinzadeh-Attar, The effect of a hydrolyzed collagen-based supplement on wound healing in patients with burn: A randomized double-blind pilot clinical trial, Burns, Volume 46, Issue 1, 2020, Pages 156-163,ISSN 0305-4179, https://doi.org/10.1016/j.burns.2019.02.015. [14] Friedman, A., et al. (2019). A Head-to-Head Comparison of Topical Collagen Powder to Primary Closure for Acute Full-Thickness Punch Biopsy-Induced Human Wounds: An Internally Controlled Pilot Study. Journal of Drugs in Dermatology. [15] Kim, J. Y., & Park, Y. H. (2017). Stem cell-derived exosome containing high amount of growth factors (World Intellectual Property Organization Patent No. WO2017123022A1). Google Patents. 3/20/2024 Comments Telomeres: tiny caps with big impact![]()
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
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This consequently affects both health and beauty
FACTORS INFLUENCING TELOMERE SHORTENING Sleep quality Poor sleep quality significantly impacts telomere length:
INTERVENTIONS FOR TELOMERE PRESERVATION 1. Possible strategies to preserve telomere length
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:
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]
A study showed that diet, exercise, stress management, and social support could increase telomere length by approximately 10% over five years [20].
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
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].
RNAi technology in development RNAi-based skincare approaches could target genes involved in telomere maintenance or have effects on markers related to telomere biology:
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.
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]:
Mechanisms of skin cell senescence:
The presence of senescent cells accelerates the ageing process due to their communication with nearby cells through various molecules: [18]
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]
Skin care ingredients: [18]
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
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Many of the skin regenerating or rejuvenating treatments, like energy based devices in the doctors-office are based on the principle to cause controlled damage and therewith provocation of a skin rejuvenating repair response. One of the fascinating mechanisms behind laser "damage" is the heat shock response leading to increased production of regenerating heat shock proteins (HSPs). Heat shock proteins respond to heat stress, are crucial cellular defence mechanisms against stress (environmental and physiological), act as chaperones, aiding in protein folding, prevention of protein damage, cellular protection and repair, with other words HSPs play a crucial role in proteostasis. [1]
HEAT SHOCK PROTEINS AND OX-INFLAMMAGEING UV radiation and blue light cause oxidative stress and inflammation, and can overwhelm skin's own capacity to counteract the increased formation of reactive oxygen species (ROS) and inflammatory mediators. Chronic oxidative stress state and chronic low grade of inflammation are hallmarks of skin ageing and their combination can be called ox-inflammageing. Oxidative stress and inflammation alter cellular signal transduction pathways and thereby the expression of the ECM genes as well as the structure of the ECM proteins like collagen, fibronectin and elastin. Their reduced expression and increased degradation manifests eventually at the skin surface as wrinkles, loss of firmness, and elasticity. Heat shock proteins are chaperone proteins that facilitate the formation of the ECM and prevention of molecular oxidative damage or degradation and are classified based on their molecular weights.
HEAT SHOCK PROTEINS AND PROTEOME Proteostasis, or protein homeostasis, refers to the balance between protein synthesis (like collagen, fibronectin and elastin), folding, and degradation. As we age, this balance is disrupted, leading to the accumulation of misfolded and aggregated proteins [10]. Loss of proteostasis is another hallmark of aging and HSPs play a crucial role in maintaining proteostasis through several mechanisms: 1. Protein folding: HSPs assist in the proper folding of newly synthesised proteins and refolding of misfolded proteins [10][11]. 2. Protein degradation: HSPs collaborate with the ubiquitin-proteasome system and autophagy to target misfolded proteins for degradation [10][12]. 3. Stress response: Under stress conditions, HSPs are upregulated to protect cells from protein damage and maintain cellular functions [13][14]. HSP-70 and HSP-90 are particularly important in protein folding and refolding, while small HSPs are involved in preventing protein aggregation [11][14]. Several studies have provided evidence supporting the potential of HSPs as an intervention to improve proteostasis: lifespan extension: [15], neuroprotection (HSP70), stress resistance and cellular survival [13][14], protein aggregation prevention (small HSPs) [11][14], autophagy regulation and particularly HSP70 is crucial for cellular protein quality control [16]. STIMULATION OF REJUVENATING HEAT SHOCK PROTEINS Heat shock protein synthesis can be initiated not only by heat but also by many chemical and physical stimuli, such as heavy metals, amino acid analogues, oxidative stress, viral infection and UV and ionizing irradiation. [17] Exercise and hormesis: Mild stress induced by exercise or other hormetic interventions has been shown to upregulate HSPs and improve proteostasis. Laser Laser treatments have been shown to induce a heat shock response in the skin from epithelial cells to deeper connective tissues, leading to the production of heat shock proteins. This response is characterized by the temporary changes in cellular metabolism, release of growth factors, and increased cell proliferation and thus contribute to tissue regeneration and rejuvenation. [17] CBD It has been proven that a large number of genes belonging to the heat shock protein super-family were up-regulated following cannabidiol (CBD) treatment. [18] UV radiation Ultraviolet radiation (UV)‐induced cell death and sunburn cell formation can be inhibited by previous heat shock exposure and UV itself can induce HSP expression. However, levels of HSP-27 have been found to be elevated in sun‐protected aged skin indicating a link between HSP-27 expression and age‐dependent epidermal alterations. [19] I would recommend daily protection from UV radiation and blue light (or high energy visible light). Ultrasound Ultrasound exposure at different frequencies, intensities, and exposure times can induce HSP-72 expression. Higher ultrasound frequencies, such as 10 MHz, have been found to significantly increase HSP-72 levels. Additionally, increasing the temperature during ultrasound exposure has shown to enhance HSP-72 expression. Interestingly, ultrasound at 1 MHz was unable to induce HSP-72 significantly, while 10 MHz ultrasound induced HSP-72 after 5 minutes of exposure. [16] Radiofrequency Radiofrequency has been shown to increase HSP-70 and decrease melanin synthesis and tyrosinase activity. [20] RF-US treatment significantly increased levels of HSP47 proteins. [21] Red & near infra red light Although I've not seen much peer reviewed published evidence, red light and near infra red light therapy may release the HSPs in the skin if tissue reaches >42 - 45 degrees (even for 8 - 10 seconds). Nicotinamide Nicotinamide and its derivatives have been found to stimulate the expression of heat shock proteins, including HSP-27, HSP-47, HSP-70, and HSP-90 in the skin. These proteins play as mentioned before an essential role in collagen production, skin protection, skin health and rejuvenation. [6] NAD as nutrient interestingly has proven to tweak the epigenome by modulating DNMT1 enzymatic DNA methylation and cell differentiation. [22] In topical applications an ingredient called Dihydromyricetin also called Epicelline® has been successful in inhibiting DNMT1 enzyme activity biochemical assays. [23] Stimulation of heat shock proteins offers a promising and novel invasive, non invasive and topical approach for skin regeneration, rejuvenation, reduction of ox-inflammageing and prevention of loss of proteostasis. 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
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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]
Effective homeodynamic space or buffering capacity (body's ability to maintain stability or balance in changing conditions) is characterized by:
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:
Hormetins can be categorized into three types:
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
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Hair is a powerful factor in how we're perceived by others and even how we see ourselves. It plays a significant role in the perception of youth and attractiveness. Studies have shown that hair style, color, and quality can significantly affect how old we look and how attractive we're considered [1]. Research suggests that hair is one of the most defining characteristics of our appearance, with the potential to make us look years younger or older [1]. From an evolutionary perspective, lustrous hair has long been associated with youth, health, and fertility [1]. Culturally, hair has been a symbol of beauty and status across societies for centuries [2].
HAIR GENETICS BEYOND MATERNAL INHERITANCE We have approximately 5 million hair follicles distributed across our bodies, with only about 100,000 located on the scalp [3][4]. Contrary to popular belief, hair characteristics are not solely inherited from one's mother. Human genetic makeup consists of 23 pairs of chromosomes, including the sex-determining X and Y chromosomes [5]. Females typically have two X chromosomes (with one usually inactivated through a process called X-chromosome inactivation), while males have one X and one Y chromosome [6]. Our hair's characteristics, including texture, color, and growth patterns, are determined by about 600 genes [7]. Interestingly, only 11% of these genes are located on the X chromosome [8]. The majority of genes influencing hair traits are found on autosomes (non-sex chromosomes), contributing to the inheritance patterns observed in families [9]. For instance, genes like EDAR and FGFR2 have been associated with hair thickness in Asian populations, while TCHH has been linked to hair texture in individuals of Northern European ancestry [10]. Research has identified several genes on the X chromosome that play a role in male pattern baldness, including the androgen receptor (AR) gene. Telomere length in hair follicle stem cells correlates with hair growth capacity and may be a biomarker for hair follicle aging. The complexity of hair genetics extends beyond sex chromosomes, involving multiple autosomal genes, environmental factors, hence epigenetics, and this is great news as changes in epigenetic patterns are partially reversible! Epigenetics Epigenetics refers to heritable changes in gene expression that occur without alterations in the DNA sequence itself [11]. Environmental factors, diet, lifestyle, chronic stress, sleep, circadian rhythms, physical activity, aging and even social interactions can influence gene expression through four main epigenetic mechanisms:
These epigenetic mechanisms can significantly impact hair biology
Example of change in epigenetic pattern Ever wondered why hair starts growing in odd places as we age? It is a good example of epigenetic changes. As we get older, changes in our epigenome can cause regions of our DNA that are normally silent (due to histone modifications) to become readable. In essence, we're becoming more like our ancient ancestors! This is why some people start growing more hair in places like ears and noses as they age. Epigenetic changes can thus silence or activate hair growth-related genes, potentially contributing to hair loss or promoting regeneration. Thus, the future of our hair health is literally (at least partially) in our hands today!. Lifestyle changes and hair regrowth Lifestyle modifications have demonstrated impacts on hair regrowth, particularly in early stages of hair loss and for prevention. 1. Nutrition: A balanced diet rich in proteins, vitamins (especially biotin, vitamins A, C, and D), and minerals (iron, zinc) has been associated with improved hair growth [20]. Supplementation with these nutrients has shown benefits in treating telogen effluvium and other hair loss conditions [21]. 2. Stress Management: Chronic stress can lead to telomere shortening and premature hair follicle aging. Stress reduction techniques like meditation and yoga have been linked to increased telomerase activity, potentially benefiting hair growth. 3. Exercise: Regular physical activity improves blood circulation to the scalp, potentially enhancing nutrient delivery to hair follicles. A study found that moderate exercise was associated with increased expression of hair growth-related genes. 4. Sleep: Adequate sleep is crucial for maintaining healthy hair growth cycles. Sleep deprivation has been linked to increased oxidative stress and inflammation, which can negatively impact hair follicles. Studies have shown promising results in targeting epigenetic mechanisms for hair loss treatment
In office therapies 1. Low-Level Laser Therapy (LLLT): LLLT works by decreasing nitric oxide enzyme activity, leading to a beneficial "micro-stress" in mitochondria. This hormetic effect increases energy production, allowing stem cells to stay young and rejuvenate. Clinical studies have demonstrated improved hair density and thickness with LLLT in androgenetic alopecia patients. 2. Platelet-Rich Plasma (PRP) and exosomes: These regenerative therapies deliver growth factors and signaling molecules to hair follicles, potentially reversing miniaturization and promoting the anagen phase. PRP has shown promising results in multiple clinical trials for androgenetic alopecia. 3. HydraFacial Keravive scalp treatment: A 3-step process involving cleansing, exfoliating, and nourishing the scalp to improve hair follicle health. 4. Hair Transplantation: Includes techniques like Follicular Unit Extraction (FUE) and strip harvesting to transplant hair from donor areas to balding areas. 5. Scalp micropigmentation: A cosmetic tattooing procedure that creates the appearance of a fuller head of hair. 6. Corticosteroid Injections: Used primarily for treating alopecia areata by injecting steroids directly into affected areas of the scalp. 7. Microneedling: Uses small needles to create micro-injuries in the scalp, potentially stimulating hair growth when combined with topical treatments. 8. Scalp Reduction: A surgical procedure that removes bald areas of the scalp and stretches hair-bearing skin. 9. Mesotherapy: Involves injecting vitamins, minerals, and other nutrients directly into the scalp to nourish hair follicles. BALD AINT BAD (for men)
Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for your particular skin or hair condition. Take care! Anne-Marie
The picture I used for this post is from my lovely daughter, who is blessed with fabulous hair.
References
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If you've scrolled through Instagram, you may have caught a glimpse of dermatologists raving about LED masks emitting red light, the secret, evidenced based weapon behind skin rejuvenation known as photo biomodulation. It uses low-powered light within the red to near-infrared range (wavelengths from 632 to 1064 nm) to induce a biological reaction aka stimulate cellular processes. The wonders of red light, also known as LLLT (low-level laser therapy), PBM (red light photo-biomodulation), or PBMT (photo-biomodulating therapy), extend far beyond non-invasive skin rejuvenation. I am not a fan of devices for home use, mostly because of lacking safety and/or efficacy, PBM definitely earned it's prominent spot in my skincare routine.
A summary of the benefts of red light with and without near infrared light for skin Numerous studies have demonstrated the effectiveness of red and infrared light therapy for skin rejuvenation. A combination of red light and near IR light has proven to stimulate the production of collagen (I & III) plus elastin production (Li WH et al Int J Cosmet Sci 2021), enhance mitochondrial ATP production, cell signaling, growth factor synthesis, rebalance ROS (reactive oxidative species) and reduce inflammation. Stem cells can be activated allowing tissue repair and healing. Wrinkle and scar reduction was observed and it can reduce UV damage both as treatment and prophylactic measure. In pigmentary disorders such as vitiligo, it can increase pigmentation by melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity (Pinar Avci et al. Semin Cutan Med Surg. 2013 & Mitchell J Winkie et al. Review Photodermatol Photoimmunol Photomed A focused review of visible light therapies for vitiligo 2024). It has the potential to activate both keratinocytes (epidermis) and fibroblasts (epidermal junction and dermis). With consistent use, you can expect a reduction of lines and wrinkles, improvement of skin tone and texture. PBMT (when done effective and safe) will compliment both your skin rejuvenating and regenerating at home skincare regimen and in-office procedures or even post-surgical skin recovery. ATP ATP (adenosine triphosphate) is the primary source of energy for cellular processes and plays a crucial role in various biological functions. When red light with specific wavelengths (630 nm to 638 nm and 810 nm) is absorbed by the skin cells, it stimulates the mitochondria, which are the powerhouses of the cells responsible for ATP synthesis. This increase in ATP production is providing cells with more energy to carry out their functions effectively and has several beneficial effects on the skin like boosting cellular metabolism, promoting more efficient nutrient uptake and waste removal. The increased ATP levels facilitate collagen synthesis by fibroblasts, a vital component for skin structure, elasticity and firmness and reduction of lines and wrinkles.. ATP aids in the repair and regeneration of damaged skin cells. It accelerates the healing process, making it beneficial for wound healing, post-surgical recovery, and addressing skin issues such as acne scars. ROS (Reactive Oxidative Species) By modulating ROS levels, red light therapy helps reduce oxidative stress and its detrimental effects on the skin. ROS are highly reactive molecules that are naturally produced by cells as byproducts of metabolic processes. While low levels of ROS play important roles in cellular signaling and immune responses, excessive ROS can lead to oxidative stress and damage to cells and tissues. Restoring the balance of ROS result in improved skin health, reduced inflammation, and enhanced skin rejuvenation. Red light therapy has been shown to modulate reactive oxidative species (ROS) levels in the skin by promoting antioxidant defense mechanisms and reducing oxidative stress:
The difference between LLLT and PBM LLLT refers specifically to the use of lasers, which produce coherent, focussed and an intense beam of monochromatic light, while PBM has a broader range of light sources, may include laser as well as light-emitting diodes (LEDs) and other non-laser devices. LEDs are often used in PBM because they are cost effective, versatile and have the ability to cover large treatment areas. LLT uses higher power densities with more energy and has a shorter treatment duration in comparison to PBM to achieve desired therapeutic effects. While there are similarities in terms of mode of action", there is a difference of light source, treatment application and parameters. Based on consensus, PBM and PBMT are considered the correct way to describe this photonic specialty for therapeutic applications. In this post I will focus on PBM and specifically LEDs. A home device claiming to use cold near infrared laser light or Low-Level Laser Therapy is called LYMA laser. It is sold for several thousand euro´s. LED masks and LED panels LED masks specifically produced by the brand Omnilux (FDA cleared) are currently very popular for very good reasons; they are safe and effective when the LEDs emit the right wavelengths and used in the recommended frequency. Omnilux combines 2 therapeutically effective and complimentary wavelengths: 633nm and near-infrared 830 nm. Both wavelengths (more precise 630nm + 850nm) I would recommend to minimally look for in any red LED device, which will disqualify most LED masks and panels in the market! I've include some (not affiliated) links to devices below. Both masks and panels can be effective, however most panels are stronger in comparison to masks 60 mW/cm² vs mW/cm²), hence have the benefit of a shorter treatment time to get a similar result. Intensity and power of red light therapy devices are typically measured in terms of irradiance (measured in milliwatts per square centimeter, mW/cm²) and radiant flux (measured in watts, W), which quantify the amount of light energy emitted by the device. Wearing a mask during a hot summer or in a warmer climate will make you sweat and depending on the materials of the mask and straps, they may be very uncomfortable to wear. Panels have the benefit that they give a more even distribution of emitted light as masks are worn on the face and thus the LED bulbs are pushed on a small skin surface area, panels can cover a larger area (depending on their size) and are more versatile in use, as area's like neck, décolletage, or knees are easier to treat with a panel. With a mask you may be more mobile, although I would not recommend walking around while using the mask. My personal preference would be a panel for the reasons mentioned before and panels are more suitable (more hygienic) for family sharing. My son can use it after an intense workout to speed up his recovery and I like to use it for purposes beyond photo-biomodulation or skin rejuvenation, for example to improve my sleep. With a panel I get more "bang for my buck". ![]()
Red light and NIR (Near Infra Red light) have the ability to penetrate varying depths of the skin, resulting in distinct benefits, thus combinations of wavelengths will provide complementary effects.
630 nm Wavelength This wavelength is often used for its skin rejuvenation benefits. It has a relatively shallow penetration depth and is absorbed closer to the surface of the skin primarily affecting the epidermis. 630nm light is associated with increased circulation, reduce inflammation, improved skin tone & texture, aiding in the delivery of nutrients and oxygen to skin cells, and stimulating the production of collagen, leading to improved skin elasticity and a reduction of the appearance of fine lines & wrinkles. 660 nm Wavelength At 660nm, red light can penetrate a little deeper into the skin, reaching the dermis. It is known for its ability to stimulate collagen production, enhance cellular metabolism, and promote anti-inflammatory effects, helping to reduce redness and inflammageing. It also promotes wound healing, making it beneficial for post-surgical or post-trauma skin recovery. 810 nm Wavelength Improve healing & recovery & accelerate wound healing. 830 nm Wavelength Accelerate healing, reduce infection, improve aesthetic outcome following plastic surgery, increase endorfines (mood-enhancing), improve bone repair and growth. 850 nm Wavelength Improve general inflammation body, enhance muscle recovery, improve wound healing, reduced fine lines, wrinkles and hyperpigmentation. Always consult a qualified healthcare professional or dermatologist to determine if and what the most suitable red light therapy approach is for your particular skin condition and rejuvenation goals. Take care! References: Hamblin, Michael R. "Mechanisms and applications of the anti-inflammatory effects of photobiomodulation." AIMS biophysics 4.3 (2017): 337-361. Barolet, Daniel. Regulation of Skin Collagen Metabolism In Vitro Using a Pulsed 660 nm LED Light Source: Clinical Correlation with a Single-Blinded August 2009Journal of Investigative Dermatology 129(12):2751-9 Wunsch A, Matuschka K. (2014). A controlled trial to determine the efficacy of red and near-infrared light treatment in patient satisfaction, reduction of fine lines, wrinkles, skin roughness, and intradermal collagen density increase. Journal of Cosmetic and Laser Therapy, 16(5), 232-237. Avci P, et al. (2013). Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Seminars in Cutaneous Medicine and Surgery, 32(1), 41-52. Links to some devices which combine 630 nm and 850 nm: FDA-approved devices ensure safety and regulatory compliance, however the panels are more powerful: Omnilux(tm) Mask (FDA clearance) Very affordable panel (no FDA clearance) Affordable panel (no FDA clearance) ![]()
Skin ageing is a biological degenerative process, marked by loss. The number of patients seeking nonsurgical rejuvenation of the face and the body is continuing to increase due to a growing ageing population concerned with physical appearance. Women wish to maintain a youthful appearance and attractiveness represent 92% of all cosmetic procedures.(1) Men are keen to maintain physical characteristics associated with virility.(2) Millennials are also increasingly concerned with preserving their beauty and youth.(3) Among the various treatment approaches, different minimally invasive techniques have been developed and dermal fillers currently come second after botulinum toxin type A (BTA).(3) Their use is increasing worldwide.
"The fear of looking done is the number 1 reason why patients don't seek treatment"* The range of fillers available for soft-tissue augmentation is constantly expanding. The latest advances in filler technology include bio-stimulators that exert their aesthetic effect by promoting predominantly collagenesis or biological stimulation of new collagen and sometimes also elastin production. Therewith they provide a biological answer to the skin ageing degeneration process, with gradual and often very natural results. Over the course of last years the knowledge on injectable bio-stimulators has grown, and therewith their safety and popularity as they provide subtle longer lasting results. Facial fillers can be broken into 3 main groups:
Bio-stimulating fillers promote the body’s natural production of some ECM components (mostly collagen) over a period of several months. Their differences are characterized by their property of inducing natural collagen production. SYNTHETIC BIOSTIMULATORS
Calcium Hydroxylapatite Calcium hydroxylapatite: Calcium hydroxylapatite is a type of mineral that is commonly found in human teeth and bones and in injectbales the calcium hydroxylapatite particles are suspended in a gel-like solution. The effects of this material last approximately 18 months with minimal inflammatory response. Radiesse is a biodegradable filler consisting of 30% synthetic CaHA microspheres (diameter of 25-45μm) suspended in a 70% aqueous carboxymethylcellulose gel carrier. The soluble carrier gel evenly distributes the Radiesse CaHA microspheres providing 1:1 correction and gradually dissipates leaving the microspheres at the injection site where they induce collagenesis (collagen type I and mostly collagen type III) by fibroblast activation. Animal studies have shown that this new collagen growth occurs as early as four weeks post-injection and continues for at least 12 months with an average duration of effect of 12 to 18 months, though some results have been noted 24 months post-injection. Radiesse provides both immediate (replacement volume) and long-lasting (collagen biostimulation) volume enhancement. (5) Poly-L-lactic acid PLLA is a biodegradable, bioresorbable biocompatible man-made polymer. This material has wide uses in absorbable stitches and bone screws. The effects of PLLA generally become increasingly apparent over time (over a period of several weeks) and its effects may last up to 2 years. There is an inflammatory response. PLLA is an alpha hydroxy acid polymer of the lactic acid L-enantiomeric structure that has been safely used in many applications and in medicine for more than 30 years. Its use has expanded worldwide, associated with good long-term aesthetic results thanks to its biostimulatory-collagen effect. PLLA-based fillers are supplied as a lyophilized powder to be reconstituted with sterile water. The collagen stimulatory properties were evidenced in human in subjects (n=14) who received PLLA injections (3 sessions, spaced 4 weeks apart) at the postauricular level by collagen histochemical determination on biopsies taken at different times. Increase of collagen type-I was shown at 3 and 6 months. This study opened the new class of collagen stimulators. The long duration of action was demonstrated in a first pivotal study comparing PLLA versus collagen (116/117 subjects, respectively); the long-term safety/efficacy was shown up to 25 months. The rationale for several sessions was first documented in a dedicated article; this modality allows the effect through collagen stimulation, a biological process to occur and avoids overcorrection. PLLA fillers are among the most clinically documented products. (6) Polymers, polycaprolactone The PCL-based collagen stimulator is composed of PCL microspheres suspended in a carboxymethyl-cellulose gel carrier providing immediate and sustained volumizing effects when injected; the morphology, the biocompatibility of the PCL microspheres embedded with the collagen fibers produced all contribute to the creation of a unique 3D scaffold for a sustained effect. Its safety has been investigated in clinical studies and vigilance surveys. It presents the advantage of a slower degradation than polylactic acid (PLLA) or polyglycolic acid (PGA), which both belong to the same chemical family. Both the S and M products induced collagen production. In animal, the M product induced collagen type-III and type-I at early stage (measure at 9 months), and later predominantly collagen type-I, that deposits around the PCL microspheres (measure at 21 months). Many fibroblasts were found near the PCL microspheres. Interestingly, new elastin fibers were also formed, and neovascularization with new capillaries observed as well. (7) NATURAL BIOSTIMULATORS 1. Platelet rich plasma 2. Platelet rich fibrin 3. Polynucleotides like Nucleofill or Nucleadyn 4. Exosomes 5. Alginate 6. Tropoelastin (precursor of elastin molecule) 7. Poly-y-glutamic acid Platelet-Rich Plasma (PRP): PRP treatments are produced by spinning a small volume of the patient’s own blood through a centrifuge. This separates and concentrates the blood’s components, including platelet-rich plasma and the “buffy coat,” a solution that contains immune cells. The provider combines these two components with a small amount of calcium chloride (which activates and keeps the PRP stable), then injects them into the treatment area. Over a period of months, PRP stimulates the body’s natural collagen production. Platelet-Rich Fibrin (PRF): PRF is produced using a process similar to PRP concentration. The active material is a fibrin matrix rich in platelets, stem cells, and immune cells. Like PRP, PRF treatment stimulates collagen production and is also implicated in tissue regeneration, though there’s less data on the durability of its effects. Because both treatments use material from the patient’s own body, so there’s no risk of rejection or similar complications. PRF and PRP effects are durable — typically lasting longer than 18 months. Polynucleotides: Polynucleotides are most often natural, highly purified DNA molecules extracted for example from trout gonads and activate specialised cells called myofibroblasts and adipocytes. PN containing devices act as short time temporary fillers thanks to the viscoelasticity of the long DNA fragments and improve skin well‐being (cell growth) and steady self‐repair (tissue regeneration). Read more Exosomes: The use of exosomes at the Aesthetic & Anti-Aging Medicine World Congress in Monaco was discussed during many session and some excellent results were presented. However their use is not yet approved and safety and long-term effect not yet established and largely depends on the source. Read more BOTULINUM TOXIN There is evidence that the neuromodulator or musclerelaxer Botinumtoxin after injection upregulated the expression of type I collagen, decreases the production of some MMPs in fibroblasts, preventing collagen degradation and improves collagen organisation. (8.9.) ENERGY BASED DEVICES Intense Pulsed Light/BroadBand Light, Radiofrequency Microneedling, lasers, High-Frequency Ultrasound, Electromagnetic Tec. stimulate collagen production via a controlled damage and repair mechanism. DERMO-COSMETICS WITH BIO-ACTIVES There are innovative dermo-cosmetic products containing bio-stimulating ingredients, working more superficial in comparison to in-office treatments and they therefor are potentially an excellent choice as adjunctive care for biological rejuvenation and revitalization for younger looking and acting skin. They are safe to use easy to apply over face, neck and décolletage. Unlike in-office treatments their effects are temporary (fully reversible as regulated), hence they require daily or twice daily application. Biostimulating active ingredients in skincare which have shown to particularly stimulate the fibroblast are for example:
VITAMIN C IS NEEDED FOR COLLAGEN SYNTHESES! Our skin needs Vitamin C to produce collagen and is not able to produce it, thus relies on external resources for supply. Therefore I highly recommend to either get enough Vitamin C from your diet or use a high quality topical product pre & post biostimulators. Read more BIOSTIMULATION FAT CELLS Renuva is an allograft adipose matrix injectable that offers a non-surgical solution for volume restoration in various areas of the body, including the face, hands, and areas with contour irregularities. It stimulates the growth of own fat cells, potentially providing longer-lasting results. Renuva is FDA-regulated. In skincare the ingredient Magnolol or Magnolia Bark Extract has shown to increase the number and size of adipocites or fat cells to counteract volume-loss. As the biological degeneration takes place in different layers of the skin and it's underlying structures, combining in-office treatments specifically targeting those layers in a series of treatments may provide longer lasting results and give higher patient satisfaction.(13) Safety and outcome rely on the qualification and experience of your cosmetic doctor, dermatologist or plastic surgeon. Take care Special thanks MD FAAD Hassan Galadari Jair Mauricio Cerón Bohórquez M.D. References: 1. American Society Plastic Surgeons. 2020 national plastic surgery statistics; 2020. 2. Wat H, Wu DC, Goldman MP. Noninvasive body contouring: a male perspective. Dermatol Clin. 2018;36(1):49–55. 3. Wang JV, Akintilo L, Geronemus RG. Growth of cosmetic procedures in millennials: a 4.5-year clinical review. J Cosmet Dermatol. 2020;19(12):3210–3212. 4. Evaluation of the biostimulatory effects and the level of neocollagenesis of dermal fillers: a review. Haddad S, Galadari H, Patil A, Goldust M, Al Salam S, Guida S International Journal of Dermatology, 29 Apr 2022 5. J Clin Aesthet Dermatol. 2015 Jan; 8(1): 38–49. Calcium Hydroxylapatite Over a Decade of Clinical Experience Jani Van Loghem, MD, Yana Alexandrovna Yutskovskaya, MD,b and WM. Philip Werschler, MDc 6. Clin Cosmet Investig Dermatol. 2022; 15: 997–1019. Collagen Stimulators in Body Applications: A Review Focused on Poly-L-Lactic Acid (PLLA) Marie-Odile Christen Read more 7. Clin Cosmet Investig Dermatol. 2020; 13: 31–48. Polycaprolactone: How a Well-Known and Futuristic Polymer Has Become an Innovative Collagen-Stimulator in Esthetics Marie-Odile Christen and Franco Vercesi 8. Oh SH, Lee Y, Seo YJ, Lee JH, Yang JD, Chung HY, Cho BC. The potential effect of botulinum toxin type A on human dermal fibroblasts: an in vitro study. Dermatol Surg. 2012 Oct;38(10):1689-94. 9. El-Domyati M, Attia SK, El-Sawy AE, Moftah NH, Nasif GA, Medhat W, Marwan B. The use of Botulinum toxin-a injection for facial wrinkles: a histological and immunohistochemical evaluation. J Cosmet Dermatol. 2015 Jun;14(2):140-4 10 EADV 2022 Inhibition of extracellular matrix degrading enzymes and bio-stimulation of fibroblasts – A novel approach to mitigate the advanced degenerative process in skin aging Weise J, Vogelsang A, Sperling G, Welge V, Nölter A, Mielke H, Knott A, Harbig S, Stuhr A, Dunckel J, Warnke K, Geloven van A 11. EADV 2021 Multifaceted novel approach to increase skin’s own epidermal and 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 12. Photochemistry and Photobiology, 2005, 81: 581–587 Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract Kirstin M. Su¨del et al 13. Combination Therapy in Midfacial Rejuvenation Humphrey et al. Dermatologic Surgery 42:p S83-S88, May 2016. *AMWC 2023 Tapan Patel ![]()
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 ![]()
Polynucleotides (PNs) are a type of biomolecule that have recently gained traction in the field of skin care and aesthetic treatments. PNs are composed of multiple nucleotides, which are the building blocks of DNA and RNA. These biomolecules have shown promise in improving the appearance and health of the skin through their ability to stimulate cell growth (activate growth factors), tissue regeneration incl. collagen production, wound healing, fibroblast proliferation and have anti-inflammatory properties.
Polynucleotides (PN) are linear polymers composed of many nucleotide units and they play a key role in the storage and transmission of genetic information. There are two types of polynucleotides (aka nucleic acid) found in nature: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). As mentioned, PN are composed of nucleotides, which consist of 3 parts: a nitrogenous base, a phosphate group. and a five-carbon sugar (2'-deoxyribose in DNA or ribose in RNA). The five base nucleotides are adenine, guanine, cytosine, thymine, and uracil. A DNA molecule consists of two long polynucleotide chains composed of four types of nucleotide subunits: adenine, thymine, guanine, and cytosine, while RNA uses adenine, guanine, cytosine and uracil. REGENERATIVE AESTHETICS Regenerative aesthetics is an emerging branch of regenerative medicine with therapies or products aimed at recapturing youthful structure and function using the body's own systems. Examples of such treatments are platelet-rich plasma (PRP), the use of exosomes or polynucleotides. Dr. Kate Goldie explained soft tissue regeneration fundamentals as following: 1. Regeneration of tissue architecture (structure): tissue composition - component abundance, ratio's, position, density and biomechanics/integrity 2. Regeneration of tissue function: signaling, cell function, cellular components (incl. senescence), gene expression and molecular interaction. The 3 treatment pillars of regenerative aesthetics are: cells, biocues and bio-stimulatory scaffolds. Key superficial soft quiescent cells are the fibroblasts and adipose derived stem cells. One of the big advantages of regenerative aesthetics is by using the body's own system, the results are natural and focused on "skin health" (function) and "skin quality" (appearance). POLYNUCLEOTIDES IN REGENERATIVE AESTHETICS Polynucleotides are most often natural, highly purified DNA molecules extracted for example from trout gonads and activate specialised cells called myofibroblasts and adipocytes. PN containing devices act as short time temporary fillers thanks to the viscoelasticity of the long DNA fragments and improve skin well‐being (cell growth) and steady self‐repair (tissue regeneration). Studies support their dermal reactivating properties or their efficacy as “bioreactivating primers” of skin. The final outcome is more natural and in‐depth tissue regeneration and a healthier look of the skin: a more radiant complexion, even skin tone, reduced appearance of fine lines, wrinkles and sagging, faster wound healing, improved pore size and skin thickness, elasticity and hydration. Furthermore, PNs are generally well-tolerated by the skin and have a low risk of adverse effects. Their effectiveness may vary depending on the individual's skin type, age, and overall health. The long-term effects of PNs on the skin are not yet fully understood, and more research is needed to determine their safety and efficacy. There are various brands available which use polynucleotides in their (meso-) injection gels. For example Mastelli Srl, Italy NEWEST® (Polynucleotide and Hyaluronic Acid) for bio-revitalization, BR Pharm HP Cell Vitaran Skin Healers, NUCLEADYN® or Nucleofill®. One brand of (synthetic) polynucleotide-based skin care products is Yuva by Dr. Devgan Scientific Beauty. The Yuva line includes a range of products formulated with PNs, such as the Yuva Serum and the Yuva Enhancer. These products are marketed as being able to provide hydrating, anti-aging, and skin-rejuvenating benefits. THE FUTURE OF POLYNUCLEOTIDES While polynucleotides have many benefits, they also have some drawbacks. One of the primary limitations is their instability in certain environments. This instability can make it difficult to synthesize and manipulate polynucleotides in the lab. Moreover their are limitations, risks and ethical concerns harvesting or using (human identical) PN's, and long-term safety and efficacy data is not conclusive. However, PNs are a promising area of research in the field of skin care and aesthetic treatments and regeneration. We can expect to see further advancements in the development of PNs-based products and treatments. PNs are already used in combination with other biomolecules, such as hyaluronic acid, growth factors and anti-oxidants and used in combination with other treatments. For a personal recommendation on which aesthetic treatment is most suitable to aesthetically regenerate your skin, please consult an experienced board certified dermatologist, plastic surgeon or cosmetic doctor. Take care. |
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