 Vitamin C is one of the best researched skincare ingredients and is well-known for its significant benefits for the skin. It is the most abundant (primary) anti-oxidant in human skin [1] and necessary for collagen production. However, we are not able to synthesize vitamin C ourselves, as humans lack the enzyme L-gulonolactone oxidase necessary for synthesizing Vitamin C [2]. Thus we rely on food, supplementation or topical application [3]. 10% vitamin C in your serum is 200 x more concentrated than 1 orange. There are many compelling reasons to incorporate vitamin C in your skincare regimen, whether you are twenty or eighty. 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. Vitamin C´s efficacy is dose-dependant, more efficacy in higher concentrations, which range between 3-20%. If you´re considering a collagen stimulating (or biostimulating) aesthetic treatment, it is highly recommended to have vitamin C either in your diet or skincare regimen (day, night or both). This is beneficial for younger, however especially more mature rejuvenators as vitamin C levels are lower in mature or photo-damaged skin [4]. More vitamin C is found in epidermis which is the top layer of the skin compared to the deeper layer or dermis [5]. Oxidative stress (from pollutants or UV irradiation) is associated with depleted vitamin C levels in the epidermal layer [6]. Topical ascorbic acid is favored in the practice of dermatology [1]. Vitamin C has multiple benefits, it enhances production of barrier lipids – decreasing TEWL (transepidermal water-loss) [7] , supports differentiation of keratinocytes (skin regeneration) [8] and protects keratinocytes from apoptosis (cell death), thus increases cell survival [9], supports wound healing, and increases dermal papillae. Dermal papillae provide nutrients and oxygen to the epidermis through their rich vascular network, support epidermal-dermal adhesion, and play a crucial role in regulating hair follicle development and cycling.
 THE ROLE OF VITAMIN C IN COLLAGEN PRODUCTION 1. Transcriptional activation: Vitamin C directly activates transcription factors involved in collagen synthesis. Research indicates that it stabilizes pro-collagen messenger RNA (mRNA), which regulates the expression of type I and type III collagen genes, particularly COL3A1. This stabilization enhances the overall production of collagen in fibroblasts. [10] 2. Hydroxylation: Vitamin C acts as a cofactor for prolyl and lysyl hydroxylases, enzymes necessary for the post-translational modification of collagen precursors. Hydroxylation of proline and lysine residues is essential for the stability and proper folding of collagen molecules. A deficiency in vitamin C leads to improper collagen formation, resulting in weakened connective tissues. [11] 3. Epigenetic regulation: Recent studies suggest that vitamin C can modulate gene expression through epigenetic mechanisms, influencing chromatin structure and accessibility. This regulation allows for enhanced transcription of collagen-related genes, thereby promoting collagen synthesis. [12] THE ROLE OF VITAMIN C IN PREVENTION OF COLLAGEN DEGRADATION Vitamin C not only plays a role in collagen synthesis but also influences its degradation: 1. Inhibition of matrix metalloproteinases (MMPs): Vitamin C has been shown to inhibit the activity of MMPs, particularly MMP-1 and MMP-12, which are responsible for collagen degradation. By reducing MMP activity, vitamin C helps maintain collagen levels in the skin. [13] [14] [15] 2. Oxidative stress reduction: As an antioxidant, vitamin C protects collagen (and other components, cells and our DNA) from oxidative damage caused by free radicals. This protection is vital for preserving the structural integrity of collagen fibers over time. [2] VITAMIN C FORMS IN SKINCARE Vitamin C is a vital ingredient in skincare, celebrated for its antioxidant properties, ability to stimulate collagen production, and other skin benefits. However, various forms of vitamin C differ in their stability, penetration, safety, and effectiveness. 1. L-Ascorbic Acid (LAA) ▌Penetration: High; penetrates the skin effectively but requires a low pH for optimal absorption. [16] ▌Stability: Prone to oxidation; degrades quickly when exposed to light and air. [17] ▌Safety and tolerability: Can cause irritation, especially at higher concentrations (esp. above 20%). [18] ▌Mode of action: Directly stimulates collagen synthesis and acts as a potent antioxidant. [19] ▌Effect on collagen: Increases collagen production by stabilizing pro-collagen mRNA and activating transcription factors involved in collagen synthesis. [20] LAA enhances the expression of collagen genes, particularly COL3A1, contributing to improved skin firmness and elasticity. [16] ▌Antioxidative capacity: Excellent; neutralizes free radicals effectively. ▌Other benefits: Brightens skin tone, reduces hyperpigmentation, increases dermal pappilae, smoother skin texture and reduced roughness thus enhance overall skin texture, hydration, reduce inflammation [21], can improve the effectiveness of sunscreens [22] Pros: Highly effective; significant evidence supporting its efficacy. Cons: May irritate sensitive skin; requires careful storage.  2. Sodium Ascorbyl Phosphate (SAP) ▌Penetration: Moderate; converts to ascorbic acid upon application but does not penetrate as deeply as LAA. ▌Stability: More stable than LAA; less prone to oxidation. [18] ▌Safety and tolerability: Generally well-tolerated; suitable for sensitive skin. ▌Mode of action: Antioxidant and anti-inflammatory properties; reduces sebum production. ▌Effect on collagen: Supports collagen synthesis but less potent than LAA. ▌Antioxidative capacity: Good; provides antioxidant protection but less effective than LAA. ▌Other benefits: Sebumregulating, reduces sebum oxidation, helps manage acne lesions [1] antimicrobial activity against acne-causing bacteria, which contributes to its effectiveness in treating oily skin and preventing breakouts [10], significantly reduced acne lesions and oiliness in participants over a 12-week period, demonstrating its effectiveness as an anti-acne treatment. [23] Pros: Gentle on the skin; stable formulation. Cons: Less potent than LAA; may not provide the same level of collagen stimulation, however more suitable for oily skin acne prone skin types. 3. Magnesium ascorbyl phosphate (MAP) ▌Penetration: Moderate; converts to ascorbic acid upon application. ▌Stability: Highly stable; retains efficacy longer than LAA. [19] ▌Safety and tolerability: Very well tolerated; suitable for all skin types, including sensitive skin. ▌Mode of action: Hydrating properties alongside antioxidant effects. ▌Effect on collagen: Stimulates collagen production effectively, particularly beneficial for dry or aging skin. ▌Antioxidative capacity: Good; protects against oxidative stress. ▌Other benefits: Improves skin hydration and soothes irritation. Pros: Hydrating; stable and effective at lower concentrations. Cons: May be more expensive than other forms. 4. Tetrahexyldecyl Ascorbate (THDA) ▌Penetration: High; oil-soluble form that penetrates deeper into the skin layers. ▌Stability: Very stable against oxidation and degradation. [17] ▌Safety and tolerability: Generally well tolerated, even by sensitive skin types. ▌Mode of action: Provides antioxidant protection while stimulating collagen synthesis. ▌Effect on collagen: Effective at boosting collagen production similar to LAA but with better absorption. ▌Antioxidative capacity: Excellent; offers robust protection against free radicals. ▌Other benefits: Enhances skin texture and brightness. Pros: Superior penetration and stability; effective for anti-aging. Cons: May be more costly due to formulation complexity. 5. Ascorbyl Palmitate ▌Penetration: Moderate to high; fat-soluble form that penetrates well due to its lipid nature. ▌Stability: More stable than LAA but less potent overall. [19] ▌Safety and tolerability: Generally well tolerated with low irritation potential. ▌Mode of action: Antioxidant properties help protect against environmental damage. ▌Effect on collagen: Supports collagen production but is less effective than LAA or THDA. ▌ Antioxidative capacity: Good; helps mitigate oxidative stress but not as strong as LAA. ▌Other benefits: Improves skin texture and reduces fine lines. Pros: Stable formulation with lower irritation risk. Cons: Less effective for collagen stimulation compared to other forms. 6. Ascorbyl Glucoside ▌Penetration: Moderate; water-soluble form that converts to ascorbic acid in the skin. ▌Stability: Highly stable against oxidation compared to LAA. [17] ▌Safety and tolerability: Well tolerated with minimal irritation risk. ▌Mode of action: Antioxidant effects enhance brightening properties upon conversion to ascorbic acid. ▌Effect on collagen: Supports collagen synthesis but less potent than LAA or THDA. ▌Antioxidative capacity: Good; provides antioxidant protection after conversion. ▌Other benefits: Brightens dull complexions effectively. Pros: Stable and gentle option for sensitive skin. Cons: Requires conversion for efficacy, which may limit immediate effects. 7. 3-O-Ethyl Ascorbic Acid (EA) ▌Penetration: Good; water-soluble derivative with enhanced skin penetration compared to L-ascorbic acid (AA) [24][25]. ▌Stability: Highly stable against oxidation due to the ethyl group modification, making it more resistant to degradation than AA [24][26]. ▌Safety and tolerability: Generally well-tolerated, with only rare cases of allergic contact dermatitis reported [25]. ▌Mode of action: Potent antioxidant that converts to vitamin C (AA) in the skin, offering enhanced free radical scavenging and skin brightening properties [24][26]. ▌Effect on collagen: Stimulates collagen synthesis by promoting procollagen I and III gene transcription, similar to AA after conversion [27]. ▌Antioxidative capacity: Excellent; exhibits strong DPPH radical scavenging ability with an IC50 value of 0.032 g/L [26]. ▌Other benefits: Demonstrates skin brightening effects, aids in repairing sun damage, and shows anti-inflammatory properties [24][27]. Pros: Highly stable, easily absorbed by the skin, and offers multiple skin benefits and good tolerability. Cons: May be less potent than pure AA in some aspects, as it requires conversion in the skin. NEW DELIVERY AND STABILIZATION SYSTEMS FOR TOPICAL VITAMIN C 1. Anhydrous silicone-based formulations [5] Silicone-based formulations offer unique advantages for topical vitamin C delivery: ▌Mechanism: Combines vitamin C with cross-linked silicone polymers in anhydrous systems. ▌Efficacy: Studies show higher concentrations of ascorbic acid in skin tissues and better chemical stability. Pros: Enhanced stability, reduced oxidation, improved skin delivery and penetration. Cons: Potential for heavier skin feel affecting consumer acceptance. 2. Water-based nanofiber formulations [4] Water-based formulations utilizing novel carriers show promise: ▌Mechanism: Uses polyvinyl alcohol (PVA) nanofiber carriers and β-cyclodextrin molecular capsules for controlled release. ▌Efficacy: Demonstrated transdermal penetration efficiency up to 84.71% after 24 hours. Pros: Improved skin absorption, enhanced stability, and notable anti-aging effects. Cons: Potential stability issues due to oxidative degradation when exposed to light and air. 3. Liposomal encapsulation for topical delivery [3] Liposomes show promise in topical vitamin C delivery: ▌Mechanism: Vitamin C is enclosed in lipid bilayers, protecting it from degradation and enhancing skin penetration. ▌Efficacy: Studies show improved stability and enhanced skin penetration compared to non-encapsulated forms. ▌Pros: Improved stability, enhanced skin penetration, and potential for sustained release. Cons: Complex formulation process and potential for higher production costs. 4. Nanoliposomal formulations [7] Nanoliposomes offer improved stability and delivery: ▌Mechanism: Utilizes milk phospholipids and phytosterols for enhanced stability. ▌Efficacy: Encapsulation efficiency up to 93% has been achieved. Pros: Increased stability and controlled release of vitamin C. Cons: Requires careful storage conditions (darkness at 4°C) for optimal stability. 5. Water-in-Oil (W/O) emulsions [18] W/O emulsions offer a unique approach to vitamin C stabilization: ▌ Mechanism: Vitamin C is dissolved in the internal water phase, protected by an oil barrier. ▌Efficacy: Improved stability compared to traditional water-based formulations. Pros: Enhanced stability and potential for improved skin feel. Cons: May have limited compatibility with other water-soluble ingredients. 6. Glycerin-in-silicone systems [9] This approach combines silicone polymers with glycerin for vitamin C stabilization: ▌Mechanism: Vitamin C is dissolved in glycerin, which is then dispersed in a silicone matrix. ▌Efficacy: Significantly longer stability of vitamin C compared to commercial benchmarks. Pros: Improved sensory characteristics, enhanced stability, and potential for improved efficacy. Cons: May require specialized formulation techniques. Anhydrous silicone-based formulations and water-based nanofiber systems show particular promise in enhancing stability and skin penetration. Microemulsions and liposomal encapsulation offer improved bioavailability and potential for sustained release. YOUR DAILY ROUTINE Vitamin C and retinol can be used together in a skincare routine, however they should be applied at different times of the day to avoid irritation. Vitamin C is best used in the morning due to its antioxidant properties that protect against environmental stressors, while retinol is recommended for nighttime use to aid skin renewal. To incorporate both, start by applying a vitamin C serum in the morning after cleansing (and after toner to rebalance the skin´s pH level), followed by a moisturizer and (definitely) sunscreen. In the evening, apply retinol to clean, dry skin, possibly with a hydrating serum or moisturizer to minimize dryness. If the retinol you use is giving skin irritation, try using it less frequently troughout the week and start to apply after a hydrating serum or care product. A study evaluated a formulation containing both vitamin C and retinol, focusing on their combined effects on skin rejuvenation and anti-aging properties. This trial assessed a regimen with 0.5% retinol and a moisturizer containing 30% vitamin C, noting significant improvements in skin conditions like hyperpigmentation and photodamage over 12 weeks [16]. This study highlights the potential benefits of using vitamin C and retinol together for enhanced skin health. [9] INCOMPATIBILITIES Vitamin C is generally compatible with many skincare ingredients, however using vitamin C with alpha hydroxy acids (AHAs) or beta hydroxy acids (BHAs), or post some procedures might cause irritation due to increased skin sensitivity or disrupted barrier. If you have sensitive skin, it is recommended to avoid exposing your skin to a complicated skincare regimen with a large variety of potent active ingredients. Irritation is your skin “telling” you to stop and rethink your regimen. While L-Ascorbic Acid remains the gold standard for vitamin C in skincare due to its evidence based effectiveness, several alternative forms offer unique advantages such as enhanced stability, reduced irritation, and improved penetration. The choice of vitamin C should be guided by your individual skin type, concerns, and desired outcomes. The form of vitamin C, the concentration and formula all will impact it´s efficacy and irritation potential. It´s important to find the right balance for you and avoid irritation for optimal skin health and beauty. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and goals. Take care Anne-Marie [1] Huang, Y., Zhang, Y., & Chen, N. (2023). Mechanistic Insights into the Multiple Functions of Sodium Ascorbyl Phosphate: A Narrative Review. Biomedicines, 11(5), 1234. doi:10.3390/biomedicines11051234. [2] Carr, A. C., & Maggini, S. (2017). Vitamins C and E: Beneficial effects from a mechanistic perspective. Frontiers in Immunology, 8, 1-15. doi:10.3389/fimmu.2017.01916. [3] Lee, C., et al. (2013). Delivery of vitamin C to the skin by a novel liposome system. Journal of Cosmetic Science, 64(1), 11-24. [4] Hu, Y., et al. (2023). Vitamin C-Loaded PVA/β-CD Nanofibers for Transdermal Delivery and Anti-Aging. ACS Omega, 8(2), 2446-2456. [5] Pinnell, S. R., et al. (2001). Topical L-ascorbic acid: percutaneous absorption studies. Dermatologic Surgery, 27(2), 137-142. [6] Lee, J. H., & Kim, Y. J. (2017). Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications. Antioxidants, 6(4), 94. doi:10.3390/antiox6040094. [7] Amiri S, et al. (2018). New formulation of vitamin C encapsulation by nanoliposomes: production and evaluation of particle size, stability and control release. Food Science and Biotechnology, 28(2):423-432. [8] Eeman, M., et al. (2016). Case Studies for the Use of Silicone Chemistry in Topical Formulations. Dow Corning Corporation. [9] Herndon JH Jr, Jiang LI, Kononov T, Fox T. An Open Label Clinical Trial to Evaluate the Efficacy and Tolerance of a Retinol and Vitamin C Facial Regimen in Women With Mild-to-Moderate Hyperpigmentation and Photodamaged Facial Skin. J Drugs Dermatol. 2016 Apr;15(4):476-82. PMID: 27050703. [10] Lee, S. Y., & Kim, J. H. (2022). Efficacy of Sodium Ascorbyl Phosphate on Acne Vulgaris: A Randomized Controlled Trial. Journal of Cosmetic Dermatology, 21(3), 1205-1211. doi:10.1111/jocd.14356. [11] Prockop, D. J., & Kivirikko, K. I. (1995). Ascorbate requirement for hydroxylation and secretion of procollagen. Journal of Biological Chemistry, 270(19), 11731-11734. doi:10.1074/jbc.270.19.11731. [12] De La Rosa, M. A., & Sosa, J. (2023). Vitamin C and epigenetics: A short physiological overview. Medical Journal of Cell Biology, 12(1), 1-8. doi:10.1515/med-2023-0688. [13] Kleszczyńska, H., et al. (2003). Influence of flavonoids and vitamins on the MMP- and TIMP-expression of human dermal fibroblasts after UVA irradiation. Photodermatology, Photoimmunology & Photomedicine, 19(5), 253-259. doi:10.1111/j.1600-0781.2003.00067.x. [15] Jacob, R.A., & Sotoudeh, G. (2001). Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in human skin. Journal of Investigative Dermatology, 117(5), 1184-1190. doi:10.1046/j.0022-202x.2001.01484.x. [16] Huang, Y., Zhang, Y., & Chen, N. (2024). Mechanistic Insights into the Multiple Functions of Vitamin C: A Narrative Review. Biomedicines, 12(1), 123. doi:10.3390/biomedicines12010001. [17] Kumar, S., & Gupta, R. (2024). Niacinamide: A versatile ingredient in dermatology and cosmetology. *PMC*. doi:10.1007/s12325-024-02046-z. [18] Draelos, Z. D., & Thaman, L. A. (2016). The anti-aging effects of niacinamide: A review of clinical studies. *Dermatology Times*. Retrieved from https://www.dermatologytimes.com/view/anti-aging-effects-niacinamide. [19] Hsieh, C., Lin, Y., & Chen, Y. (2023). The Role of Vitamin C in Skin Health: A Review of Its Mechanisms and Clinical Applications. Antioxidants, 12(2), 203. doi:10.3390/antiox12020203. [20] Wu, M., Cronin, K., & Crane, J. (2022). Biochemistry, Collagen Synthesis. In StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507709/. [21] PMC. (2015). The Roles and Mechanisms of Actions of Vitamin C in Bone: New Developments. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC4833003/ [22] Topical Vitamin C and the Skin: Mechanisms of Action and Clinical Applications: This review article discusses the photoprotective effects of topical vitamin C and its role in enhancing the efficacy of sunscreens (Huang et al., 2017). Available at PMC5605218. [23] Kwon, H., & Kim, J. (2021). Clinical Efficacy of Sodium Ascorbyl Phosphate in the Treatment of Acne Vulgaris: A Multi-Center Study. Dermatology, 237(4), 456-462. doi:10.1159/000515678. [24] Cosmacon GmbH. "3-O-Ethyl Ascorbic Acid (Vitamin C Derivative)." Cosmacon Glossary, 2025. [25] Iliopoulos F, Sil BC, Moore DJ, Lucas RA, Lane ME. 3-O-ethyl-l-ascorbic acid: Characterisation and investigation of single solvent systems for delivery to the skin. Int J Pharm X. 2019 Jul 19;1:100025. doi: 10.1016/j.ijpx.2019.100025. PMID: 31517290; PMCID: PMC6733298. [26] Liao, W. C., Huang, Y. T., Lu, L. P., & Huang, W. Y. (2018). Antioxidant Ability and Stability Studies of 3-O-Ethyl Ascorbic Acid, a Cosmetic Tyrosinase Inhibitor. Journal of Cosmetic Science, 69(4), 233-243. [27] Boo YC. Ascorbic Acid (Vitamin C) as a Cosmeceutical to Increase Dermal Collagen for Skin Antiaging Purposes: Emerging Combination Therapies. Antioxidants (Basel). 2022 Aug 26;11(9):1663. doi: 10.3390/antiox11091663. PMID: 36139737; PMCID: PMC9495646.
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 The process of autophagy in which a lysosome engulfs and digests excess or damaged cellular material.
Autophagy was initially classified under "altered proteostasis" as part of the hallmarks of aging. However as autophagy is involved in various other aspects of aging, such as DNA repair and metabolism, it's now seen as an "integrative hallmark". Autophagy is the cell´s way of cleaning up and recycling it´s own parts to maintain health and efficiency [1] by breaking down various parts of the cell, such as proteins, fats, and small structures called organelles. This breakdown happens in special compartments within the cell called lysosomes, which contain enzymes that can digest these cellular components. Impaired autophagy is a cause of aging and not just a consequence. When the efficiency of autophagy declines, it contributes to the accumulation of damaged cellular components, affecting other hallmarks of aging and the progression of health and beauty (skin health) problems [1][2].
SIMPLIFIED HOW AUTOPHAGY WORKS
▌Initiation: The process begins when a cell is under stress, such as during nutrient deprivation or oxidative stress. ▌Formation of the autophagosome: A double-membrane structure called a phagophore forms and expands to engulf damaged or unnecessary cellular components. ▌Encapsulation: The phagophore completely surrounds the targeted cellular material, forming a sealed vesicle called an autophagosome. ▌Fusion with lysosome: The autophagosome travels through the cell and fuses with a lysosome, forming an autophagolysosome - see picture below ▌Breakdown and recycling: Inside the autophagolysosome, lysosomal enzymes break down the captured cellular material into basic building blocks like amino acids, fatty acids, and nucleotides. ▌Reuse of materials: The broken-down components are released back into the cell's cytoplasm, where they can be reused to build new cellular structures or generate energy. THREE MAIN TYPES OF AUTOPHAGY (illustration) A. Macroautophagy: The most common form, involving the formation of autophagosomes that engulf cellular components and fuse with lysosomes for degradation. B. Chaperone-mediated autophagy: Selective degradation of specific proteins with the help of chaperone proteins. D. Microautophagy: Direct engulfment of cytoplasmic material by lysosomes. Various impairments in these autophagy mechanisms can occur: ▌Autophagosome formation ▌Decreased lysosomal function ▌Impaired fusion of autophagosomes with lysosomes ▌Accumulation of non-degradable material in lysosomes These impairments lead to the accumulation of damaged cellular components, contributing to the aging process. CONSEQUENCES DECLINE AUTOPHAGIC ACTIVITY
 Illustration showing the fusion of a lysosome (upper left) with an autophagosome during the process of autophagy.
GENERAL CAUSES IMPAIRED AUTOPHAGY - HEALTH
Disruption of key regulatory pathways Autophagy is tightly regulated by several molecular pathways, and disruption of these can impair the process: ▌Nutrient sensing pathways: Inhibition of AMPK and SIRT1 or activation of mTOR can suppress autophagy initiation [1][5]. ▌Mutations affecting proteins like ULK1, Atg13, or other autophagy-related genes can disrupt autophagosome formation [5]. ▌Dysregulation of transcription factor TFEB, which controls expression of autophagy and lysosomal genes, can impair the process [1][5]. Defects in autophagosome formation or maturation Problems with the machinery involved in forming or maturing autophagosomes can impair autophagy: ▌Disruption of membrane sources like the ER or mitochondria can affect autophagosome formation [6]. ▌Mutations affecting proteins involved in autophagosome-lysosome fusion, like Dynein, can block completion of autophagy [6]. Lysosomal dysfunction Since lysosomes are crucial for the degradation step of autophagy, lysosomal defects can severely impair the process: ▌Lysosomal storage disorders, like Pompe disease, directly impair the degradative capacity of lysosomes [1]. ▌Accumulation of undegraded material in lysosomes can overwhelm their function over time [1]. Cellular stress and damage Various cellular stressors can both induce and potentially overwhelm autophagy: ▌Oxidative stress and mitochondrial dysfunction can both trigger and potentially impair autophagy if severe [7][8]. ▌Accumulation of protein aggregates, as seen in neurodegenerative diseases, can overwhelm autophagic capacity [6][7]. Metabolic imbalances Disruptions in cellular metabolism can impair autophagy: ▌Chronic exposure to excess nutrients, like in obesity or alcoholic liver disease, can suppress autophagy through mTOR activation [1][5]. ▌Energy deficits can potentially impair autophagy if severe enough to disrupt basic cellular functions [5]. In many cases, impaired autophagy results from a combination of these factors, often creating a vicious cycle where initial dysfunction leads to further cellular stress and damage, progressively worsening autophagic impairment over time [1][7][8]. This is particularly evident in age-related and neurodegenerative diseases, where multiple factors converge to disrupt cellular homeostasis and autophagic function. SKIN AGING Autophagy impairment contributes significantly to skin aging through multiple mechanisms: [9] ▌Reduced collagen and elastin production by fibroblasts ▌Accumulation of damaged ECM components ▌Altered keratinocyte differentiation and reduced barrier function (thinning) ▌Reduced stem cell function and altered cellular metabolism ▌Accumulation of cellular damage and reduced stress resistance Impaired autophagy in fibroblasts and keratinocytes leads to wrinkles and reduced skin elasticity [10][11] and more visible signs of aging skin. SKIN SPECIFIC CAUSES IMPAIRED AUTOPHAGY - BEAUTY Autophagy decline was observed in both intrinsic and extrinsic skin aging [12]. Oxidative stress and environmental factors Skin cells are constantly exposed to environmental stressors that can impair autophagy: ▌Ultraviolet (UV) radiation is a major factor that can disrupt autophagy in skin cells, particularly keratinocytes and melanocytes [13][14]. ▌Reactive oxygen species (ROS) generated from various environmental factors can deactivate key autophagy regulators like Akt and mTORC1, leading to impaired autophagy initiation [15]. Aging and senescence As skin cells age, their autophagic capacity tends to decline: ▌Premature skin aging is associated with decreased autophagy in various skin cell types [13]. ▌Senescence of mesenchymal cells in the dermis is linked to impaired autophagy and contributes to skin aging [14]. Dysregulation of autophagy pathways Several molecular pathways can become dysregulated, leading to impaired autophagy: ▌Mutations or alterations in autophagy-related genes (ATGs) can disrupt the formation of autophagosomes and impair the process [15][16]. ▌Dysfunction of the mTORC1 signaling pathway, a key regulator of autophagy, can lead to autophagy impairment [17]. Cellular energy imbalances Disruptions in cellular metabolism can impair autophagy in skin cells: ▌Low cellular energy levels (high AMP/ATP ratio) can abnormally trigger AMPK activation, disrupting normal autophagy regulation [17]. ▌Nutrient imbalances can affect mTORC1 activity, which is crucial for proper autophagy function [17]. Inflammatory processes Chronic inflammation in the skin can interfere with normal autophagy: ▌Inflammatory skin conditions like psoriasis and atopic dermatitis are associated with impaired autophagy in various skin cell types [16][17]. Lysosomal dysfunction Since lysosomes are crucial for the final stages of autophagy, their dysfunction can severely impair the process: ▌Accumulation of undegraded material in lysosomes, which can occur with aging or in certain skin conditions, can overwhelm lysosomal function and impair autophagy completion [15][14]. ROLE OF UV AND BLUE LIGHT IN AUTOPHAGY IMPAIRMENT IMPLICATIONS FOR SKIN HEALTH AND PHOTOAGING UV Radiation and autophagy: UV exposure has a complex effect on autophagy in skin cells. Acute UV exposure activates autophagy as a protective mechanism. This process helps degrade oxidized lipids and metabolic wastes, potentially slowing photoaging. However, chronic UV exposure leads to autophagy impairment and accelerated skin aging [13]. UV radiation modulates several signaling pathways involved in regulating autophagy: [14] [18] 1. mTOR (mechanistic target of rapamycin): A negative regulator of autophagy 2. AMPK (AMP-activated protein kinase): Promotes autophagy 3. PI3K/Akt pathway: Influences autophagy regulation 4. p53: Plays a role in UV-induced autophagy response UV exposure also affects the expression and activity of autophagy-related genes like Atg5, Atg7, and LC3 [14]. The UV-induced DNA damage and oxidative stress contribute significantly to autophagy dysfunction over time. Blue light and autophagy: ▌Blue light induces approximately 50% of the oxidative stress in skin cells compared to UV. ▌It penetrates deeper into the skin, affecting both epidermal keratinocytes and dermal fibroblasts. ▌Prolonged exposure may lead to autophagy impairment, contributing to premature skin aging and pigmentation issues. Molecular mechanisms and key players: [14] Several molecular mechanisms and key players are involved in the UV-autophagy relationship:
AUTOPHAGY AND DNA REPAIR Autophagy plays a crucial role in maintaining cellular homeostasis and genomic stability, particularly in skin health and DNA repair [19]. When UVB radiation hits our skin, it activates AMPK, which in turn boosts the autophagy process in our cells [18]. This mechanism is essential for repairing various types of DNA damage, including broken DNA strands, small structural changes, and errors that occur during DNA replication [20]. Autophagy positively regulates the recognition of DNA damage by nucleotide excision repair (NER) and enhances the repair of UV-induced lesions, particularly through the removal of oxidized proteins and lipids [21]. By responding to various DNA lesions and regulating multiple aspects of the DNA damage response (DDR), autophagy helps maintain the integrity of our genetic material and promotes overall skin health. IMPACT ON SKIN CELLS The skin, being the largest organ, is significantly affected by impaired autophagy, which impacts various skin cells differently, leading to visible signs of aging such as wrinkles, reduced skin thickness, and pigmentation changes. Ethnic differences in autophagy capacity may influence susceptibility to skin damage [12]. Autophagy has different effects in three categories of skin cells: [13] ▌stem cells: autophagy supports self-renewal and quiescence. Declining autophagy can lead to stem cell loss over time. ▌short-lived differentiating cells: like keratinocytes, autophagy contributes to differentiation processes like cornification but is less impacted by aging. ▌long-lived differentiated cells (hair follicles and sweat glands): autophagy maintains cell survival and function. Decreased autophagy leads to accumulation of damaged components. The roles of autophagy in skin aging are complex and cell type-specific [13]. Keratinocytes Keratinocytes, the primary cell type in the epidermis, rely heavily on autophagy for differentiation and barrier function [16]. Different autophagy proteins showed distinct localization patterns in the epidermis [12]. LC3 and ATG9L1 were enriched in granular layers, while ATG5-ATG12 and ATG16L1 were in basal/spinous layers [12]. Autophagy plays a critical role in keratinocyte cornification, the process by which these cells form the outermost layer of the skin. Autophagy protects keratinocytes against UV-induced DNA damage and inflammation, potentially slowing photoaging [13]. Impaired autophagy in keratinocytes can lead to: ▌Reduced barrier function ▌Increased susceptibility to environmental stressors [14] ▌Altered epidermal differentiation ▌Accumulation of damaged proteins and organelles ▌Increased DNA damage, senescence, and aberrant lipid composition after oxidative stress [14][22]. mTOR inhibition directly promoted keratinocyte differentiation [12]. Fibroblasts Dermal fibroblasts are responsible for producing extracellular matrix (ECM) components, including collagen and elastin. Fibroblast autophagy helps clear lipofuscin (age pigment) and damaged proteins that accumulate with age. Autophagy impairment in fibroblasts can result in: ▌Reduced proteostasis and ECM production (collagen and elastin production) [13] ▌Accumulation of senescent cells and DNA damage [13] ▌Increased matrix metalloproteinase (MMP) activity, leading to ECM degradation ▌Altered cellular metabolism and energy production ▌Accumulation of autophagosomes, resulting in the deterioration of dermal integrity and skin fragility [10][11] These changes contribute to the formation of wrinkles and loss of skin elasticity [14]. Melanocytes Melanocytes, responsible for skin pigmentation, are particularly sensitive to autophagy impairment [13]. Autophagy defects disturb melanosome biogenesis and transport, leading to pigmentation disorders. Autophagy-deficient melanocytes display a senescence-associated secretory phenotype (SASP), contributing to inflammation and pigmentation changes [23]. Declining melanocyte autophagy may contribute to age-related pigmentation changes and hair graying. The consequences of impaired autophagy: ▌Accumulation of damaged melanosomes ▌Altered melanin production and distribution ▌Increased susceptibility to oxidative stress, inflammation and senescence ▌Pigmentation disorders like vitiligo and hyperpigmentation Stem cells Skin stem cells, including those in hair follicles and the interfollicular epidermis, rely on autophagy for maintenance and function. Impaired autophagy in stem cells can lead to: ▌Reduced self-renewal capacity ▌Altered differentiation potential ▌Accumulation of damaged cellular components ▌Premature stem cell exhaustion These effects contribute to reduced skin regeneration and repair capacity with age [14]. Sweat glands and sebaceous glands Autophagy is essential for normal sebum production in sebaceous glands (long-lived cells) and in sweat glands suppresses accumulation of lipofuscin ("age pigment") during aging and maintains gland function [13]. Autophagy plays a crucial role in the function of sweat glands and sebaceous glands. Impairment can result in: ▌Reduced sweat production, affecting thermoregulation ▌Altered sebum composition and production - can affect skin barrier function and contribute to conditions like acne [24] ▌Increased susceptibility to infections and skin disorders Merkel cells Autophagy regulates serotonin signaling in Merkel cells and may impact age-related changes in touch sensation [13]. Hair follicles In hair follicles, (long lived cells) autophagy promotes hair growth [14] and may counteract age-related hair loss when pharmacologically activated [13]. PIGMENTATION Dysregulation of autophagy in melanocytes affects melanin synthesis and transfer, leading to pigmentation disorders [23]. Autophagy activity correlates with skin lightness measurements and plays a role in melanosome degradation in keratinocytes . autophagy proteins like LC3, p62, ATG9L1, ATG5-ATG12 and ATG16L1 were decreased in hyperpigmented skin, while mTORC1 activity was increased in hyperpigmented elbow skin [12]. Autophagy impairment can lead to various pigmentation disorders: [12] ▌Hyperpigmentation: Accumulation of damaged melanosomes and altered melanin distribution ▌Hypopigmentation: Potential link to vitiligo through increased melanocyte sensitivity to oxidative stress ▌Uneven skin tone: Dysregulation of melanin production and transfer to keratinocytes Restoring autophagy (inhibiting mTORC1 with Torin 1) improved both pigmentation (maintaining skin color uniformity) and epidermal differentiation (barrier function) [12] and could be a therapeutic approach for photoaging and hyperpigmentation. PIGMENTATION ISSUES 1. Senile Lentigo (Age Spots): Studies have shown that autophagy declines in hyperpigmented skin areas such as senile lentigocompared to even-toned skin [12]. This decline in autophagy is associated with increased melanin deposition and melanocyte proliferation in the epidermis [13]. The impaired autophagy in these areas also correlates with reduced levels of late epidermal differentiation markers like filaggrin and loricrin [13]. 2. Photoaging: Ultraviolet (UV) radiation, a major cause of photoaging, affects autophagy in skin cells. While UV exposure initially increases autophagy as a protective mechanism, chronic exposure leads to impaired autophagic function. This impairment contributes to the accumulation of damaged cellular components and oxidized proteins, accelerating the photoaging process [14][12]. 3. Xerotic hyperpigmentation: In areas of skin with severe xerosis (dry skin) and hyperpigmentation, an exacerbated decline in autophagy has been observed. This decline is accompanied by severe dehydration and barrier defects, showing correlations with deteriorating skin physiological conditions [13]. The impaired autophagy in these areas contributes to both pigmentation abnormalities and compromised epidermal differentiation. These examples demonstrate that impaired autophagy is associated with various aspects of skin aging, including pigmentation changes, barrier function decline, and altered epidermal differentiation. The decline in autophagic activity appears to be both a result of aging processes and a contributing factor to the progression of skin aging symptoms [12][13][14]. SOLAR ELASTOSIS Solar elastosis is characterized by the accumulation of abnormal elastotic material (broken elastin fibres due to sun damage) in the dermis. While not directly linked to impaired autophagy, the loss of autophagy and/or it's housekeeping partner proteasome could be a contributing factor. 1. Autophagy is crucial for cellular homeostasis: Autophagy is described as "an essential cellular process that maintains balanced cell life" and is responsible for "clearing surplus or damaged cell components notably lipids and proteins" [12]. 2. Impaired autophagy in photoaging: Loss of autophagy leads to both photodamage and the initiation of photoaging in UV exposed skin [12][18]. 3. UV radiation affects autophagy: UV exposure can both stimulate and impair autophagy, depending on the circumstances. For example, repeated UVA radiation negatively affects the autophagy process in fibroblasts due to modifications in lysosomal functioning [25]. 4. Accumulation of damaged components: When autophagy is impaired, there's a reduced ability to clear damaged cellular components. This could include broken down elastin fibres. The proteasome and autophagy work closely together in cleaning up and recycling proteins like elastin. 5. Chronic inflammation: Photoaging is characterized by a chronic inflammatory response, which can be exacerbated by defects in autophagy. In turn, defects in autophagy have also been shown to cause severe inflammatory reaction in the skin [12]. AUTOPHAGY FAT CELLS Autophagy in fat cells, or adipocytes, plays a significant role in regulating adipose tissue biology and metabolism. 1. Role in adipose tissue biology: Autophagy is crucial for maintaining cellular homeostasis in adipose tissue by degrading and recycling cellular components. It influences adipogenic differentiation and affects the size and function of adipose tissue depots [26]. 2. Influence of obesity: In obesity, autophagy is often altered. Adipocytes in obese individuals show increased autophagic activity, which is associated with enhanced lipid mobilization and metabolic activity [27]. This process can be influenced by proinflammatory cytokines, leading to selective degradation of lipid droplet proteins like Perilipin 1 [27]. 3. Adipocyte browning: Autophagy is involved in the browning of white adipose tissue, which is associated with increased energy expenditure and protection against obesity [28]. Suppression of autophagy can block adipogenesis and lipid accumulation, indicating its role in fat storage and metabolism [28]. 4. Response to fasting: During fasting, autophagy is upregulated in adipose tissue to promote fat breakdown and support metabolic processes like ketogenesis [29]. This response involves the regulation of genes that influence autophagic activity. 5. Regulation by mTOR: The mTOR signaling pathway is a major regulator of autophagy in adipocytes. Under conditions of nutrient deprivation or stress, mTOR activity is inhibited, leading to the activation of autophagy [17]. AUTOPHAGY AND INSULIN RESISTANCE Activation of autophagy is beneficial for improving insulin sensitivity without compromising insulin production [30][31]. Impaired autophagy as a cause of insulin resistance 1. Accumulation of cellular debris: When autophagy is impaired, damaged organelles and proteins accumulate in cells, leading to cellular stress and inflammation that can contribute to insulin resistance [32]. 2. ER stress: Autophagy inhibition can cause severe endoplasmic reticulum stress in adipocytes, which can suppress insulin receptor signaling and contribute to peripheral insulin resistance [33]. 3. Mitochondrial dysfunction: Impaired autophagy can lead to accumulation of damaged mitochondria, which can disrupt cellular metabolism and contribute to insulin resistance [32]. 4. Reduced insulin signaling: Knockdown of autophagy genes like Atg7 in adipocytes can reduce insulin-stimulated phosphorylation of insulin receptor subunits and IRS-1, directly impairing insulin signaling [33]. Insulin resistance as a cause of impaired autophagy 1. Hyperinsulinemia: Chronic exposure to high insulin levels, as seen in insulin-resistant states, can suppress autophagy through activation of mTORC1 and inhibition of FoxO1 [30]. 2. Nutrient excess: The excess nutrients associated with obesity and insulin resistance can inhibit autophagy through mTORC1 activation [32][33]. 3. Altered gene expression: Insulin resistance can downregulate the expression of genes encoding major autophagy components, further impairing autophagic function [34]. Bidirectional relationship The relationship between insulin resistance and impaired autophagy often creates a vicious cycle: 1. Initial insulin resistance can lead to suppression of autophagy. 2. Impaired autophagy then exacerbates cellular stress and dysfunction. 3. This cellular dysfunction further worsens insulin resistance. 4. The cycle continues, progressively worsening both conditions [32][33]. Tissue-specific effects The relationship between autophagy and insulin sensitivity can vary depending on the tissue: 1. In insulin-responsive tissues like muscle, liver, and adipose tissue, moderate activation of autophagy can improve insulin sensitivity by reducing cellular stress and inflammation [30][32]. 2. In pancreatic β-cells, however, excessive autophagy can reduce insulin storage and secretion, potentially worsening glucose intolerance despite improved peripheral insulin sensitivity [30]. PREVENTION AND TREATMENT OPTIONS Targeting nutrient-sensing pathways (mTORC1, AMPK, SIRT1) can enhance autophagic activity and mitigate age-related cellular damage [4][35][36] The most efficient and evidence-based methods to improve autophagy are: 1. Intermittent fasting (IF): ▌The 16/8 method (16 hours fasting, 8 hours eating window) is commonly recommended [37][38]. ▌Alternate-day fasting and the 5:2 diet (5 days normal eating, 2 days restricted calories) are also effective [38][39]. ▌Fasting periods of 18-72 hours show increasing benefits for autophagy [37]. Fasting a lot is not recommended for women in their reproductive age, the use of geroprotectors (a few mentioned under point 6) are more suitable. 2. Calorie restriction (CR): [4] ▌Reducing daily calorie intake by 10-40% can trigger autophagy [38]. ▌Long-term calorie restriction increases the expression of autophagy-related genes [40]. 3. Exercise: [4] ▌Both aerobic exercise and resistance training stimulate autophagy [37][41]. ▌Aerobic exercise (lower intensity, longer duration) may be more effective for autophagy than high-intensity exercise [37]. 4. Ketogenic diet: ▌A high-fat, low-carb diet can mimic fasting effects and trigger autophagy [41]. 5. Sleep: ▌Good quality sleep supports autophagy, as it follows the sleep-wake cycle [41]. 6. Specific nutrients and supplements: ▌Spermidine (naturally occurring in our body and food) has been shown to enhance autophagy [40][42] and is on top of the list. ▌Resveratrol, found in red wine and grapes, may induce autophagy [40] (in very high doses), however there are contradicting study outcomes. ▌Curcumin (from turmeric) has shown potential in animal studies [41]. ▌Green tea contains compounds that may support autophagy [40]. ▌GlyNAC - more information below 7. Stress management: ▌Chronic stress can interfere with autophagy, so stress reduction techniques like meditation or yoga may be beneficial [38]. 8. Pharmacological Interventions: ▌Several antidiabetic medicines and other pharmacological agents are being explored to modulate autophagy and slow aging [3][4]. ▌Genetic approaches to upregulate autophagy-related genes (e.g., ATG7, BECN1) are being investigated as potential therapeutic strategies for neurodegenerative diseases [35][43]. 9. Hormetic stress activates autophagy: Hormesis influences and activates autophagy through various mechanisms, contributing to cellular stress resistance and potential health benefits. ▌Hormesis appears to be executed by a variety of physiological cellular processes, including autophagy that cooperatively interact and converge [44]. ▌Hormetic heat shock activates autophagy in human RPE cells [45]. Heat shock factor 1 (HSF1) plays a role in hormetic autophagy activation [46=73]. HHS enhances the expression of fundamental autophagy-associated genes in ARPE-19 cells through the activation of HSF1 [45]. ▌Inhibition of mTOR (mechanistic target of rapamycin) is a key pathway for hormetic autophagy activation. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy [44]. ▌Hormetic autophagy contributes to stress resistance, longevity, and improved proteostasis [46]. 10. Sunscreen: I promote the use of sunscreens, particularly ones with the natural compounds Licochalcone A (powerful anti-oxidant, Nrf2 activator, Glutathione stimulator and MMP1 inhibitor) [47][48][49][50] and Glycerrhetinic Acid (supports DNA repair) [51]. The regular use of sunscreen can decrease the risk of impaired autophagy in skin: ▌Reduction of oxidative stress: By blocking UV rays, sunscreen helps prevent the generation of excessive ROS, which can impair autophagy [18]. ▌Prevention of DNA damage: Sunscreen protects skin cells from UV-induced DNA damage, which can interfere with autophagy-related gene expression [18][21]. ▌Maintenance of cellular homeostasis: By reducing overall UV-induced stress on skin cells, sunscreen helps maintain the balance necessary for proper autophagy function [21]. Several studies have demonstrated the link between UV protection and autophagy preservation. A study published in the Journal of Investigative Dermatology showed that UV radiation can dysregulate autophagy in skin cells, and that protecting against UV exposure can help maintain normal autophagy function [21]. Research published in the International Journal of Molecular Sciences highlighted that sunscreen use can prevent UV-induced damage to autophagy-related proteins and pathways in skin cells [18]. A review in Frontiers in Pharmacology discussed how sunscreen, as part of a comprehensive photoprotection strategy, can help preserve autophagy function in skin by reducing overall UV-induced cellular stress [21]. By using sunscreen regularly, individuals can significantly reduce their risk of impaired autophagy in skin cells, contributing to overall skin health and slowing the photoaging process. 11. Red light therapy: Red light therapy, particularly at a wavelength of 660 nm, has been shown to promote autophagy, the cellular process of cleaning out damaged cells and regenerating healthier ones. Studies indicate that this therapy can enhance autophagy in various contexts, such skin health [57]. Additionally, red light therapy is often used in combination with fasting to further boost cellular repair processes associated with autophagy. Red light activates autophagy in retinal cells: Studies have shown that red light exposure can activate multiple steps of the autophagy process in retinal pigment epithelium (RPE) cells. It increases autophagy-related proteins and promotes the formation of autophagosomes [58]. 12. Polynucleotides: 1. DNA damage response: DNA damage can trigger autophagy as a protective mechanism. Polynucleotides, particularly damaged DNA, can activate autophagy pathways [59]. 2. RNA-mediated regulation: Certain RNA molecules, such as microRNAs and long non-coding RNAs, can modulate autophagy-related gene expression and signaling pathways [59]. 13. Exosomes: Exosomes have a complex relationship with autophagy: 1. Autophagy regulation: Exosomes can carry proteins and RNAs that influence autophagy in recipient cells. For example, some exosomal microRNAs can target autophagy-related genes [59]. 2. Protein content alteration: Autophagy modulators can significantly alter the protein content of phosphatidylserine-positive extracellular vesicles (PS-EVs), including exosomes, produced by cancer cells [59]. 3. Signaling molecules: Exosomes can contain important signaling molecules like SQSTM1 and TGFβ1 pro-protein, which are involved in autophagy regulation [59]. 4. Intercellular communication: Exosomes derived from cells treated with autophagy modulators can influence the metabolism and phenotype of recipient cells [59]. 5. Autophagy-related protein transport: Exosomes can carry autophagy-related proteins like LC3-II, potentially transferring autophagic capabilities between cells [59]. The relationship between exosomes and autophagy is bidirectional. Autophagy can also influence exosome production and content. The specific effects may vary depending on the cell type, physiological context, and the particular polynucleotides or exosomes involved. GLYNAC AND AUTOPHAGY GlyNAC, a combination of glycine and N-acetylcysteine, has shown promising effects on various aspects of cellular health, including autophagy. Glutathione synthesis and oxidative stress GlyNAC supplementation has been shown to improve glutathione (GSH = body's master antioxidant) synthesis and reduce oxidative stress [52][53][54]. GSH is a crucial antioxidant that plays a role in regulating autophagy and DNA repair. By improving GSH levels, GlyNAC may indirectly support autophagic processes [52][53]. Aging hallmarks GlyNAC supplementation has been shown to improve multiple hallmarks of aging, including mitochondrial dysfunction, oxidative stress, and inflammation [52][53][54].[55].These improvements may indirectly support autophagic processes, as these hallmarks are interconnected with autophagy regulation [1][2]. Direct evidence on autophagy While direct evidence of GlyNAC's effect on autophagy is limited, some studies provide insights: 1. In a study on HIV patients, GlyNAC supplementation improved mitophagy markers, suggesting a potential role in enhancing selective autophagy of mitochondria [53]. 2. N-acetylcysteine, a component of GlyNAC, has been shown to induce autophagy in various cellular models, potentially through its antioxidant properties and effects on mTOR signaling [56]. Potential mechanisms The potential mechanisms by which GlyNAC might influence autophagy include: 1. Reduction of oxidative stress, which can promote autophagy induction [52][53][54]. 2. Improvement of mitochondrial function, which is closely linked to mitophagy regulation [7][8][52][53]. 3. Modulation of nutrient-sensing pathways, such as mTOR, which are key regulators of autophagy [53][56]. Future directions While the evidence suggests that GlyNAC supplementation may have beneficial effects on cellular processes related to autophagy, more direct research is needed to fully elucidate its impact on autophagic flux and regulation. By improving autophagy, we're not just investing in our appearance, but in the fundamental processes that keep our body healthy. Always consult a qualified healthcare professional to determine what the most suitable approach is for your needs and rejuvenation or regeneration goals. Take care! Anne-Marie
References:
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The Role of Autophagy in Skin Fibroblasts, Keratinocytes, Melanocytes, and Epidermal Stem Cells. J Invest Dermatol. 2020 [10] Kim H et al. (2018). Autophagy in Human Skin Fibroblasts: Impact of Age. International Journal of Molecular Sciences, 19 [11] Tashiro K. et al. Biochem. Biophys. Res. Commun. Age-related disruption of autophagy in dermal fibroblasts modulates ECM (2014) [12] Wang M et al. Autophagy: Multiple Mechanisms to Protect Skin from Ultraviolet Radiation-Driven Photoaging. Oxid Med Cell Longev. 2019 [13] Murase D. et al. Int. J. Mol. Sci. Autophagy Declines with Premature Skin Aging Altering Skin Pigmentation and Epidermal Diff. (2020). [14] Eckhart Leopold, Tschachler Erwin , Gruber Florian Autophagic Control of Skin Aging Frontiers in Cell and Developmental Biology 2019 [15] Lin Y. et al. Front. Immunol. The multifaceted role of autophagy in skin autoimmune disorders (2024). [16] Kim HJ, Park J, Kim SK, Park H, Kim JE, Lee S. Autophagy: Guardian of Skin Barrier. Biomedicines. 2022 [17] Klapan K, Simon D, Karaulov A, Gomzikova M, Rizvanov A, Yousefi S, Simon HU. Autophagy and Skin Diseases. Front Pharmacol. 2022 [18] Ma J et al. Autophagy plays an essential role in ultraviolet radiation-driven skin photoaging. Front Pharmacol. 2022 [19] Gomes LR, Menck CFM, Leandro GS. Autophagy Roles in the Modulation of DNA Repair Pathways. Int J Mol Sci. 2017 [20] Umar S.A. et al. RSC Adv. Integrating DNA damage response and autophagy in UV-B induced skin photo-damage (2020). [21] Zhong X. et al. Medicine. Role of autophagy in skin photoaging: A narrative review (2024). [22] Song X. et al. Redox Biol. Autophagy deficient keratinocytes show increased DNA damage and senescence after oxidative stress (2016). [23] Ni C. et al. Int. J. Biochem. Cell Biol. Autophagy deficient melanocytes display SASP with oxidized lipid mediators (2016). [24] Rossiter H. et al. Exp. Dermatol. Inactivation of autophagy changes sebaceous gland morphology and function (2018). [25] Gromkowska-Kępka K.J. et al. J. Cosmet. Dermatol. The impact of ultraviolet radiation on skin photoaging: in vitro studies review (2021). [26] Romero M, Zorzano A. Role of autophagy in the regulation of adipose tissue biology. Cell Cycle. 2019 [27] Ju L. et al. Cell Death Dis. Obesity-associated inflammation triggers autophagy-lysosomal response in adipocytes (2019) [28] Seung-Hyun Ro et al. Front. Physiol., 28 January 2019 Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity [29] Furthering fat loss in the fasting response - EurekAlert! Peer reviewed publication Osaka University 2022 [30] Yamamoto S et al. Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity. Cell Rep. 2018 [31] Ning Wang et al. Autophagy: Playing an important role in diabetes and its complications, Medicine in Drug Discovery 2024 [32] Frendo-Cumbo S. et al. Front. Cell Dev. Biol. Communication Between Autophagy and Insulin Action (2021). [33] Budi Y.P. et al. PeerJ. Autophagy's role in high-fat diet-induced insulin resistance in mouse adipose tissues (2022). [34] Kezhong Zhang; “NO” to Autophagy: Fat Does the Trick for Diabetes. Diabetes 1 February 2018 [35] Uddin M. et al. Front. Aging Neurosci. Autophagy and Alzheimer's Disease: Mechanisms to Therapeutic Implications (2018). [36] Cheon S. et al. Exp. Neurobiol. Autophagy, Cellular Aging and Age-related Human Diseases (2019) [37] Al-Bari M. et al. Int. J. Mol. Sci. Targeting Autophagy with Natural Products for Cancer Therapy (2021) - dr Erik Berg Youtube 2023 [38] InsideTracker. Autophagy Fasting: What You Should Know Before Starting Your Fast (2024) [39] Life MD Autophagy Fasting: What You Need to Know Before Starting Jeffrey Vacek, DNP, FNP-C 2023 [40] DECODE AGE Autophagy: Definition, Process, causes & Supplements Dec 20, 2023 By Madhulatha Kesam Reddy Naga [41]. MedicineNet How Do You Trigger Autophagy? Medical Author: Dr. Jasmine Shaikh, MD Medical Reviewer: Pallavi Suyog Uttekar, MD [42] Hofer, S.J.et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nat Cell Biol 26, 1571–1584 (2024) [43] Tan C. et al. Neurobiol. Aging. Autophagy in aging and neurodegenerative diseases (2014) [44] Moore MN. Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease. Dose Response. 2020 [45] Amirkavei M et al. Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells. Cells. 2022 [46] Kumsta C. et al. Nat. Commun. Hormetic heat stress and HSF-1 induce autophagy in C. elegans (2017) [47] Mann T. et al. Photodermatol. Photoimmunol. Photomed. HEVIS induces skin oxidative stress: Protective effects of Licochalcone A (2019) [48] Lim H.W. et al. J. Am. Acad. Dermatol. Impact of visible light on skin health: Antioxidants in skin protection (2022) [49] Ladewig S. et al. EADV Poster. Licochalcone A protects against HEV light-induced ROS and MMP-1 expression in vitro (2018) [50] Kühn J. et al. Exp. Dermatol. Licochalcone A activates Nrf2 and reduces cutaneous oxidative stress in vivo (2014) [51] Hong M. et al. J. Invest. Dermatol. Glycyrrhetinic Acid: Modulator of Skin Pigmentation and DNA-Repair (2009) [52] Kumar P. et al. Clin. Transl. Med. GlyNAC supplementation improves multiple aging-related deficits in older adults (2021) [53] Kumar P. et al. Clin. Transl. Sci. GlyNAC supplementation improves multiple aging-related deficits in older adults (2020) [54] Kumar P. et al. Antioxidants. GlyNAC improves mitochondrial function and insulin resistance in type 2 diabetes (2022) [55].Kumar P. et al. Nutrients. GlyNAC supplementation increases lifespan and corrects aging-related defects in mice (2021) [56] Sun Y. et al. CNS Neurosci. Ther. N-acetylcysteine induces mitochondria-dependent apoptosis in glioma cells (2016) [57] Yang KL et al. In vitro anti-breast cancer studies of LED red light therapy through autophagy. Breast Cancer. 2021 [58] Pinelli R. et al. Antioxidants. Light pulses and phytochemicals promote autophagy to counter oxidative stress in AMD (2023) [59] Hanelova K. et al. Cell Commun. Signal. Autophagy modulators affect signaling molecules in PS+ extracellular vesicles (2023) 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
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
Like epigenetics and exosomes, neurocosmetics represent a revolutionary approach for skin care incorporating neuroscience principles, leveraging the skin-brain connection to improve skin health and beauty. The term itself is a fusion of the words neuroscience and cosmetics. It differs from psychodermatology which like neurocosmetics connects the interaction between mind and skin, but in a different way. Some describe it as how simple sensory stimulation can improve our overall wellbeing and call it "mood beauty", however this doesn't do it justice as neurocosmetics go beyond mood boosting skincare.
DEFINITION NEUROCOSMETICS Dermatologist Professor Laurent Misery back in 2002 described that neurocosmetics are products which are supposed to modulate the neuro-immuno-cutaneous-system (NICS) function at an epidermal level. Skin cells can produce neuromediators, which are mediators for transmission of information between skin, immune and the nervous system. All skin cells express specific receptors for neuromediators and by binding of the neuromediator to its receptor, modulation of cell properties and skin functions are induced like cell differentiation and proliferation (renewal), pigmentation, etc. Hence, keratinocytes, Langerhans cells, melanocytes, endothelial cells, fibroblasts and the other cells of the skin are modulated and controlled by the nerves and in return skin is able to modulate neuronal activity and growth. [1] SKIN-BRAIN CONNECTION In an article from the International Journal of Novel Research and Developments, the skin-brain connection was described as a psychobiological concept that highlights how emotions, stress, and neurotransmitters impact skin health. Indicating that the skin acts as a neuroimmunoendocrine organ, emphasizing its sensitivity to neural signals and stress responses. [4] CUTANEOUS NERVOUS SYSTEM The skin a sophisticated sensory organ that allows you to interact with your environment through touch and feel. It contains a complex network of nerves that send information about sensations like pressure, pain, itch and temperature from the skin through the spinal cord to the brain [9]. The dynamic interactions between the skin and the nervous system is influenced by factors like stress and inflammation, which can impact skin health and ageing. [7] Nerves in the skin: These nerves are like tiny messengers that tell your brain about what your skin is feeling: pressure, heat or pain. Types of nerve fibers: Some are thick and wrapped in a protective coating, which helps them send messages quickly. Others are thin and slow but are very good at sending messages about pain or temperature changes. [3] Sensory receptors: These receptors can tell if something is touching the skin lightly or if there's a lot of pressure. They can also sense if something is hot, cold, or causing pain. [3] Autonomic nervous system: Part of the cutaneous nervous system helps control things that happen in the skin automatically, like sweating to regulate body temperature. [8] Nerve cells: There are about 20 different types of neurons in our skin. [10] The contribution of epidermal keratinocytes to NICS [3]
CUTANEOUS NEURO-AGEING Neuro-ageing is defined as the changes in the nervous system which cause continuous neurodegeneration due to oxidative stress, neuroinflammation or impaired neuromodulation. As skin ages, Aβ-toxin (increased by oxidative stress) accumulates at the nerve endings innervating the tissue, causing disrupted cellular communication, particularly affecting fibroblasts’ ability to produce collagen and extracellular matrix. On top there is a decrease of nerve growth factor (NGF) production, important for the development and maintenance of nerve cells. Different factors can lead to a drop in NGF production, resulting in malfunctioning keratinocytes and reduced lipolytic activity of adipocytes, visibly impacting skin hydration and firmness. [6] Skin nerve fibres are significantly reduced in number following UV irradiation and in ageing skin [5] and therefore neuro-protectors or targetting neurodegeneration can reduce stress manifestations and promote healthy cellular communication for optimal skin function. [3] Although not much is known regarding skin specific or topical neuroprotectors (most research was focussed on the brain), probably potent anti-oxidants, by significantly reducing oxidative stress from UV and blue light and anti-inflammatory ingredients may inhibit skin neuro-ageing and can be neuroprotective especially when combined with sunscreen and strengthening of the skin barrier. NEUROCOSMETIC VARIETY OF ACTIONS
THE FUTURE OF NEUROCOSMETICS The neurocosmetics market is booming, with a projected value of USD 2.69 billion by 2030. [11] The future of neurocosmetics holds promise for innovative ingredients and concepts that harness new neuroscientific insights to revolutionize skin care and sunscreen formulations, to cater to both physical and emotional aspects of skin health and beauty. Take care! Anne-Marie References
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
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, reduced inflammation, reduced sebum production, 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) 5/11/2023 Comments The right amount of skin care
Using the right amount of a skin care product is as important as picking the right product(s). If you don't apply enough of the product or for a too short duration, you will not get the optimal result. This is particularly crucial when using sunscreen to reach the sufficient SPF level and protection. According to a study published in the Journal of the American Academy of Dermatology by Andreas Storm MD et al. 95% of patients with a topical treatment under-dose, hence do not use enough cream.
If there is a specific user manual mentioning the dosage, or you got a prescription, follow their recommended instructions. If the product came without specific dosage instructions, there is a general rule of thumb. The recommended amount of product to apply varies, depending on the product type. THE 2 FINGERS RULE FOR SUNSCREEN For sunscreen you need 1/2 teaspoon for the face or enough to cover the bottom of a shot glass and a full shot glass for the body, which should add up to 2mg per cm2. Another method is using the "rule of nines, which is used for burns. The body areas are divided into 11 area's, each representing 9% of the total. Sunscreen can be applied to each of these areas at a dose of 2 mg/cm2 (regardless phototype) if two strips of sunscreen are squeezed out on to both the index and middle fingers from the palmar crease to the fingertips, thus 2 fingers. (1) The body areas are: 1 Head, neck, and face 2 Left arm 3 Right arm 4 Upper back 5 Lower back 6 Upper front torso 7 Lower front torso 8 Left upper leg and thigh 9 Right upper leg and thigh 10 Left lower leg and foot 11 Right lower leg and foot FINGERTIP UNITS For the use of other topical products there is a guidance created called Finger Tip Units or FTU's by CC Long and AY Finlay. It is a way of measuring the amount of product squeezed out of a tube with a 5mm diameter nozzle and applied from the distal skin-crease (the crease closed to the fingertip) to the tip of the index finger. The FTU concept has been used as a central part of an education programme for parents of children with atopic eczema, has been advocated to reduce the variation in usage of topical steroids and to encourage adherence to therapy. For a serum, you may need less as they are lightweight products which should be fully "absorbed" without residue. If the skin still feels sticky after 1 minute, you probably applied too much product. A guidance would be a pea size dot on forehead, right cheek, and left cheek, which is similar to the recommended amount of retinoids (Vitamin A). However, unlike Vitamin A, using too much serum usually isn't harmful for the skin, but increases the risk of "pilling". 
The precise number of FTU's required:
One FTU covers 286 cm2, more specifically in males and 312 cm2 in females 257 cm2. The quantity of cream in a fingertip unit varies: Adult male: 1 fingertip unit provides 0.5 g Adult female: 1 fingertip unit provides 0.4 g . Keep in mind this is a general guideline and the amount of product needed or results may vary also depending on skin type, concerns and the products particular attributes. Take care (in the right amount and duration) References: 1. BMJ. 2002 Jun 22; 324(7352): 1526.Simple dosage guide for suncreams will help users Steve Taylor et al. Illustration Tinea incognito with unjustified use of potent Topical Corticosteroids: a case series July 2017 International Journal of Basic & Clinical Pharmacology 6(8):2087 Haiya Sheth et al. 5/6/2023 Comments The impact of humidity on skin
Something I am asked quite regularly is if low humidity can dry out the skin. The answer is yes it can. However, it really depends on your skin. There are 4 skin types: normal, dry, combination and oily. According to the (AAD American Academy of Dermatology) sensitive skin is a skin type too, however some would say all skin is sensitive and I somewhat agree. Dehydrated skin is not a skin type, but a (temporary) condition. Your skin type is pretty much set for life and not changing with the seasons. There is an exception as normal, oily or combination skin may become dry(er) post-menopause. The environment, including temperatures and humidity impact our skin significantly.
Humidity Humidity is the amount of water vapor in the air. If there is a lot of water vapor in the air, the humidity will be high. A relative humidity of 70 percent means the air is at 70 percent of its water-holding capacity for the present temperature. Cold air cannot hold as much water vapor as warm air. Thus, as temperature falls, with no change in the amount of water in the air, the relative humidity rises. HIGH HUMIDITY A study showed that in a dry environment the skin hydration decreases but the amount of sebum increases to compensate for skin dryness. (1) High humidity can be beneficial if you have dry skin, however can cause problems if you have oily or combination skin. Low levels of humidity can negatively affect your skin, even when your skin is oily. In general high humidity levels has some benefits. Hydration The increased levels of moisture in the air in high humidity decrease trans-epidermal-water loss of water evaporation from the skin. Hence, your skin is able to maintain it's hydration levels. Increased cell regeneration A moisture-rich climate can also promote skin cell turnover and desquamation (the shedding of dead skin cells). Skin’s regeneration process is increased when your skin is well hydrated. The shedding of dead skin cells is the last step in this cell-turnover or regeneration process and good desquamation leads to smoother texture and more radiant skin. Well-ageing effects Fine lines and wrinkles are more noticeable if your skin lacks moisture and feels dry. Moreover, skin regeneration process declines as we age. Since high humidity positively contributes to hydration, lines and wrinkles are less pronounced and the regeneration process supported, therewith leading to more youthful looking skin. Increased sebum production If your skin is oily, high humidity (especially heat thus sweat) can increase sebum production. An overproduction of sebum, especially in combination or oily skin types can make your skin oily and greasy. Moreover, dirt and irritating particles may "stick" better to greasy skin. Acne prone skin Excess sebum and oil caused by high humidity (heat and sweat) increases the risk of clogged pores, break-outs and comedones (blackheads, and whiteheads). Heat or sweat rash Heat rash, or sometimes called prickly heat, sweat rash or miliaria, is a harmless but very itchy or prickling skin rash. It causes small red (raised) spots in places where sweat collects, such as the armpits, back, under the breasts, chest, groin, elbow creases and back of the knees, and the waist. Although uncomfortable, it is usually harmless and improves on its own after a few days. Tips to take care of your skin in humid conditions
LOW HUMIDITY Low levels of humidity most commonly negatively affect your skin. Decrease skin regeneration When your skin is not well hydrated, the skin's regeneration process including shedding of dead skin cells is impaired. This can lead to a more dull, rough or even flaky skin. Dehydrated skin Your skin can get dehydrated or deprived of moisture when exposed to low humidity levels and the skin looks less radiant or glowing. Sings of ageing When your skin lacks moisture, the skin is less plump and wrinkles, fine lines become more visible. Worsening of skin conditions If you have eczema or another problematic impaired barrier related skin condition, low humidity can cause flare-ups. It can also cause or worsen dry skin symptoms like redness, scaliness, rough texture, cracks, itchiness, stinging, burning and the skin might be more prone to irritation and infection. Tips to care care of your skin in low humidity
Take care References
We all know the fairy tail sleeping beauty, however there is actual scientific evidence supporting that good sleep does make you more attractive. Chronic poor sleep quality is associated with increased signs of intrinsic ageing, diminished skin barrier function, lower satisfaction with appearance (1). A variety of studies in the literature have shown that sleep plays a role in restoring immune system function and that changes in the immune response may affect collagen production. (2) Before going into the science supporting that sleep makes you more beautiful, some tips for better sleep and less wrinkles:
A study was conducted with 60 healthy caucasian women, who were categorised as poor quality sleepers [Pittsburg Sleep Quality Index (PSQI) > 5, sleep duration ≤ 5 h] or good quality sleepers (PSQI ≤ 5, sleep duration 7-9 h. Good sleepers had significantly lower intrinsic skin ageing scores by SCINEXA(TM) . At baseline, poor sleepers had significantly higher levels of TEWL (trans-epidermal water loss). At 72 h after tape stripping, good sleepers had 30% greater barrier recovery compared with poor sleepers. At 24 h after exposure to ultraviolet light, good sleepers had significantly better recovery from erythema (redness). Good sleepers also reported a significantly better perception of their appearance and physical attractiveness compared with poor sleepers. (1) Sleep loss could also impact sexual behaviour and collaboration, because sleep is connected with attractiveness, which has an important impact in many social contexts (2). The notion of beauty sleep is actually very important, because sleep deprived people are perceived as more fatigued, less attractive, and even less healthy than when they are rested (3). Sleep deprivation is associated with increased signs of intrinsic skin ageing (fine lines, uneven pigmentation, reduced elasticity) (4), with much slower recovery rates after skin barrier disruption and lower satisfaction with appearance. If we compare people with a normal night sleep with the same persons but sleep deprived, the sleep deprived ones look more fatigued, with hanging eyelids, redder eyes, more swollen eyes, darker circles under the eyes, paler skin, more wrinkles and fine lines around the eyes, the corners of the mouth as being more droopy and more sad (5). In conclusion, the sleep is not connected only with good health (6,7), but is also a link between attractiveness and health. (2,8) Take care and sleep well
It was always believed that the moment we are born, is the moment we are exposed to environmental influences. The truth is that there is ample evidence that already during pregnancy the mothers behaviour: smoking or food has a significant impact on how well we age. We know that all skin needs to be protected against UV and HEVIS by using sunscreen, especially in sun exposed areas from birth onwards.
Although you can not start too early taking care of your skin, the right age to start with a well-ageing skin care routine is actually just post-adolescence for 3 reasons. 1. During adolescence most start with their first cleansing and care routines to remove access of sebum, debris and reduce plus prevent break-outs or comedones. Boys may already shave facial hair. So teenagers or young adults are used to a morning- and evening skin care routine which benefits the overall sense of well-being. 2. Most commonly growth stops when puberty ends and this is the moment the degenerative biological process starts, even though there are no visible signs yet. 3. Prevention of pre-mature ageing skin is the most effective and efficient strategy. SKIN NEEDS CARE There is a movement stating that normal unproblematic skin doesn't need care. I strongly disagree. The choice of products at this age depends of course on the skin type, skin condition, skin health, and environment (like weather conditions, pollution), however the morning care should always focus on protecting every skin type, using suncreen (UV + HEVIS protection) and ideally complimented by anti-oxidants to reduce damaging free radical activity, while the evening routine should at least include proper cleansing (to remove dirt and pollutants), which may be followed by product catering to specific needs, like for example sebum regulating, barrier repairing or hydrating ingredients. I would not make a differentiation between darker or lighter skin in terms of photoprotection, as dark skin only has a natural SPF of 13.3 and light skin of 3.4, hence both not enough to prevent sun damage. However, dark skin has a lower amount of ceramides in the statum corneum and is therefore more prone to trans-epidermal water loss. LAZY SKIN? If you are afraid of spoiling your skin and making it "lazy" using skin care for a long time, know that all effects from a dermo-cosmetic product are 100% reversible, thus temporary. This is regulated by law and to enjoy the benefits from skin care, you need to keep using the products. When you stop, your skin will bounce back to it's original state at least after a full regeneration cycle of about 28 days. A few things to avoid are: sun-damage, especially burns, over-exfoliation (damaged skin barrier) and slugging of oily or acne-prone skin (breakouts). Take care. 
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. 
Glycation is one of the basic root causes of endogeneous (intrinsic) skin ageing and a very challenging one or almost impossible one to reverse. Glycation is an ageing reaction which begins in early life, developing clinical symptoms at around 30, and progressively accumulates in tissues and skin due to the glycated collagens that are difficult to be decomposed. Glycation occurs naturally in the body when sugars react with proteins and lipids to form advanced glycation end products (AGEs). AGEs can be exogenously ingested (through food consumption), inhaled via tobacco or endogenously produced and formed both intracellularly and extracellularly. AGE modifications lead to dermal stiffening, diminished contractile capacity of dermal fibroblasts, lack of elasticity in the connective tissues, contribute to hyperpigmentation and a yellowish skin appearance. The formation of AGEs is amplified through exogenous factors, e.g., ultraviolet radiation.
AGEs cause changes in the skin through 3 processes:
One study published in the Journal of Investigative Dermatology found that levels of AGEs were higher in the skin of older individuals compared to younger ones. The study also showed that there was a correlation between the level of AGEs and the severity of skin ageing. This suggests that inhibiting the production or accumulation of AGEs in the skin is a potential target for anti-ageing interventions or skin ageing management. AGEs are complex and heterogeneous, more than a dozen AGEs have been detected (however not all) in tissues and can be divided into three categories according to their biochemical properties. AGEs are formed through four pathways:
GLYCATION INHIBITION IS KEY AGEs can be crosslinked through side chains to form a substance of very high molecular weight, which is not easily degraded. The consequences from skin glycation are irreversible. This makes prevention or inhibition of the process the best potential strategy to maintain skin health and ageing skin management. One way to do this is by altering the diet to reduce the intake of sugars and carbohydrates, which are known to contribute to glycation. Several studies have found that reducing sugar intake can result in significant improvements in skin health, including reducing wrinkles and improving skin texture.  Sugar molecules bind to dermal fibers, forming advanced glycation end products (AGEs) over time Left: dermis filled with hyaluron, collagen and elastin Right: dermis with less hyaluron, broken elastin and collagen fibers
AGE inhibitors
Another potential strategy is the use of topical agents that inhibit the formation or accumulation of AGEs in the skin. One study published in the Journal of Cosmetic Science found that a cream containing carnosine, a peptide that inhibits glycation, improved skin elasticity and reduced the appearance of wrinkles in individuals with ageing skin. Skincare containing NAHP or Acetyl Hydroxyproline inhibits the formation of AGEs significantly (in vitro), most likely through a mechanism where NAHP competes with the proteins for the sugar. Finally, NAHP sacrifices itself in place of the proteins and gets (at least partially) glycated. NAHP also prevents loss of cellular contractile forces in a glycated in vitro dermis model and counteracts the diminished cell-matrix interaction that is caused by glyoxal-induced AGE formation. Take-aways from a study published in the International Journal of Cosmetic Science [2]: 1. NAHP significantly and dose-dependently inhibited the formation of advanced glycation end-products (AGEs) in a protein solution. 2. NAHP dose-dependently inhibited the formation of N-(carboxymethyl)lysine (CML), a specific AGE. 3. In fibroblast-populated collagen lattices, NAHP prevented the glycation-induced disturbance of fibroblast contractile capacity. 4. Ex vivo application of NAHP to skin explants decreased AGE fluorescence compared to glucose-treated samples. Anti-Oxidants I would suggest to combine those ingredients with an ingredient like Licochalcone A. Numerous high ranked publications support that Licochalcone A protects cells from oxidative stress mediated by e.g. UV and HEVIS (blue light) induced reactive oxidative species (ROS). Due to the activation and nuclear translocation of the transcription factor NrF2, the expression of anti-inflammatory, antioxidant and detoxifying enzymes are induced. These enzymes protect the skin cells (like keratinocytes and fibroblasts) from ROS-induced damage, like lipid peroxidation and DNA as well as protein damage. If Licochalcone A is combined with L-Ascorbic Acid, (the most active form of Vitamin C), it supporting skin's own collagen production, provides superior biological cell protection amongst other relevant benefits. Vitamin C (and E) has shown to inhibit protein glycation [4]. SPRAY TAN A study in Redox Biology indicates that sunless tanning with dihydroxyacetone (DHA) causes glycation and potential DNA damage in the epidermis [1].: 1. Glycation: DHA exposure led to the formation of advanced glycation end products (AGEs) in epidermal cells, confirmed by mass spectrometric detection of N-ε-(carboxyethyl)-l-lysine (CEL). 2. DNA damage: DHA induced a cellular stress response, including activation of stress-related genes and phosphoprotein signaling. While not directly measuring DNA damage, these responses are often associated with cellular stress that can lead to DNA damage. 3. Significance: The effects were observed at low millimolar concentrations of DHA, relevant to topical application. The stress response was rapid and pronounced, occurring within minutes of exposure. 4. Location: The effects were primarily observed in epidermal cells and reconstructs, with no mention of dermal effects. This study suggests that sunless tanning with DHA may not be as safe as previously thought, warranting further investigation into its long-term effects on skin health [1], however no need to panic as this negative effect is only seen in the top layer of the skin. DOUBLE TROUBLE: GLYCATION + UVB [3] The combination of GO-AGEs and UVB exposure has a more pronounced effect on skin inflammation and oxidative stress than either factor alone. This suggests a synergistic relationship between glycation and UV exposure in accelerating skin aging processes. 1. GO-AGEs combined with UVB irradiation significantly increased the secretion of pro-inflammatory cytokines (IL-1β, IL-6, IL-8) in skin cells compared to either GO-AGEs or UVB alone. 2. The GO-AGEs + UVB treatment group showed a more than three-fold increase in IL-6 and IL-8 mRNA levels compared to other groups. 3. GO-AGEs + UVB treatment induced significantly higher release of nitric oxide (NO) compared to other groups. 4. The combination of GO-AGEs and UVB enhanced reactive oxygen species (ROS) release, creating about 1.5 times more oxidative stress compared to control and other groups. 5. Cell viability was notably affected in the GO-AGEs, UVB, and GO-AGEs + UVB treatment groups compared to the control group. These findings are significant as they demonstrate that the combination of GO-AGEs and UVB exposure has a more pronounced effect on skin inflammation and oxidative stress than either factor alone. This suggests a synergistic relationship between glycation and UV exposure in accelerating skin aging processes. Use sunscreen daily. . GLYCATION AND SKIN HEALTH Acne In addition to its role in ageing, glycation in the skin has also been linked to a range of skin health problems. One study published in the Journal of Cosmetic Dermatology found that the level of AGEs in the skin was significantly higher in individuals with acne than in those without acne. The study also showed that treating acne with a topical antibiotic significantly reduced the levels of AGEs in the skin. Atopic Dermatitis Another study published in the Journal of Investigative Dermatology found that individuals with atopic dermatitis had higher levels of AGEs in their skin than healthy individuals. This suggests that glycation may play a role in the development of inflammatory skin conditions. Diabetes + Woundhealing The correlation between high sugar levels and skin ageing can be seen in diabetic patients, where one-third of this population has skin complications. A prominent feature of ageing human skin is the fragmentation of collagen fibers, which severely damages the structural integrity and mechanical properties of the skin. Elevated levels of MMP-1 and MMP-2 and higher crosslinked collagen in the dermis of diabetic skin lead to the accumulation of fragmented and crosslinked collagen, thereby impairing the structural integrity and mechanical properties of dermal collagen in diabetes. Collagen crosslinking makes it impossible for them to easily repair, resulting in reduced skin elasticity and wrinkles. Keratinocytes and fibroblasts are the main cells involved in wound healing, but due to the high glucose (HG) microenvironment in diabetics, the functional state of these cells is impaired, thereby accelerating cellular senescence (programmed cell death). Conclusion We can't completely stop the glycation process, therefore it's important that we inhibit it from a young age onwards, hence monitor the sugar intake of our children, use daily SPF and invest in good dermo-cosmetic products containing ingredients like NAHP and powerful anti-oxidants like L-Ascorbid Acid (Vitamin C is needed for the production of collagen) and Licochalcone A (also anti-inflammatory). Preventing signs of ageing, specifically caused by glycation is most effective. If your skin shows (advanced) signs of ageing, you can get visible improvement using skin component (hyaluron, collagen and elastin) bio-stimulating ingredients like Retinol, Bakuchiol, Arctiin, Creatine or Glycine Saponin. Consult your dermatologist if you wish to improve your skin's appearance or skin health issues. Take care Anne-Marie References [1] Perer J, Jandova J, Fimbres J, Jennings EQ, Galligan JJ, Hua A, Wondrak GT. The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis. Redox Biol. 2020 Sep;36:101594. [2] Knoblich C, et al. N‐acetyl‐L‐hydroxyproline – A potent skin anti‐ageing active preventing advanced glycation end‐product formation in vitro and ex vivo. Int J Cosmet Sci. 2023;1-10. doi:10.1111/ics.12930 [3] Sultana, R., Parveen, A., Kang, MC. et al. Glyoxal-derived advanced glycation end products (GO-AGEs) with UVB critically induce skin inflammaging: in vitro and in silico approaches. Sci Rep 14, 1843 (2024). https://doi.org/10.1038/s41598-024-52037-z [3] Sadowska-Bartosz I, Bartosz G. Prevention of protein glycation by natural compounds. Molecules. 2015 Feb 16;20(2):3309-34. doi: 10.3390/molecules20023309. PMID: 25690291; PMCID: PMC6272653. Special thanks: Ph.D. dr Julia M. Weise Manager Biological Testing & Dorothea Schweiger Lab Manager Facial Skin Biology Beiersdorf HQ Hamburg 
We all learned that sleeping in make-up is the ultimate skincare sin. What is bad about it is when you go 24 hours without washing your face and end up going to bed leaving your day-time make-up on. Over the course of the day, our skin accumulates pollutants, dirt and dead skin-cells.
If dirt and pollutants are left on the skin, they may cause micro-inflammation and contribute to premature ageing skin via a process called inflamm-aging and free-radical damage which is a major contributor to skin-ageing. The combination of both micro-inflammation and free-radical damage is called ox-inflammation. We should aim to reduce or preferably avoid it. Pollution, dirt and sebum (oils) can impact the skin's healthy pH balance and thus lead to a weakening of the skin barrier function, more sensitive skin, dehydration, slowed down skin-cell renewal process and thus ageing. Not removing dead skin cells together with dirt increases the risk of clogged pores. Make-up itself usually doesn’t contain harming ingredients. Coloured micro-pigments actually provide additional sun-protection. Make-up or foundation itself is thus not the problem, however the fact that we don’t cleanse our skin after a busy day and/or evening is what could make us age faster. Not doing your PM cleanse and care routine is anyway a missed opportunity to support your skin’s night-time recovery with beneficial active ingredients. If you go out in the evening, take the opportunity to cleanse before getting ready and get rid of debris which was accumulated during day-time. Don’t worry about falling asleep in your make-up once or twice. Just don’t make it a habit. I would always aim to remove eye make-up. Sleeping in full eye make-up (mascara, liner, eyeshadow) increases the risk of an eye-inflammation, redness and corneal abrasions. Waking up with “panda-eyes” filled with black rheum or goop isn’t pretty either. Take care 
Vitamin C is a "must have" skin care ingredient our skin needs at any age.
One of the best researched skin care ingredients and proven to be very beneficial for skin is Vitamin C. Our skin uses Vitamin C as an anti-oxidant and the dermal fibroblasts need Vitamin C for the production of collagen. Two very good reasons to add this ingredients into your daily skincare routine whether you are twenty or eighty. Moreover, our skin depends on us for the needed supply, as our skin is not able to produce Vitamin C itself. We can either include enough Vitamin C in our diet or apply Vitamin C topically there where we need it the most. Usually this is the skin which is exposed to (sunlight) as this increases damaging free radical activity in our skin. An active form of vitamin C can reduce the free radical activity, which we call anti-oxidative effect. There are 4 things to consider when buying a skincare product containing Vitamin C:
Day or night? Some recommend to use Vitamin C during the night, as the active form of Vitamin C will oxidize in daylight. Hence, your skin can benefit from the Vitamin C longer during the night. I would recommend Vitamin C to be used during daytime (thus added to your morning routine), as we need protection from damaging free radicals the most during daytime and the oxidization of Vitamin C is actually a sign that the ingredient is doing it’s job! It’s even better to add Vitamin C both to your day & night time skincare routine. Is L-Ascorbid Acid enough? Vitamin C is counteracting free radicals from UV light. However, UV is not the only damaging light form as there is also High Energy Visible Light or abbreviated HEVIS. This penetrates even deeper into the skin where also the dermal fibroblasts reside. The dermal fibroblasts are our collagen and hyaluronic acid producing cells and a key target in an effective anti-ageing skincare strategy. Lichochalcone A (Licorice-root extract) has proven to be the most potent anti-oxidant to protect the dermal fibroblasts and neutralize free radicals from HEVIS. Moreover, Lichocalcone A increases Glutathione, which is a skin’s own anti-oxidant. Licorice-root extract is an anti-ageing hero. Summary The combination of Vitamin C and Lichocalcone A will protect our skin and dermal fibroblasts from free radical damage by UV and HEVIS and will provide superior biological cell protection in comparison to Vitamin C only. For me this is a good reason to use a product containing both ingredients as a first step after my cleansing routine in the morning. If you have sensitive eyes, I recommend to use an eye care prior, which will form a barrier to help to prevent the low pH Vitamin C product to migrate into the eye area. Afterwards you can use the other products of your skincare routine. I would like to put emphasis on using a SPF of 30 or higher during the day. This will not only help to protect your skin, but also support the anti-oxidative benefits and make them last longer. Hope this was helpful. Take care! 
One of the frequently asked questions is, if it's necessary or if there is a benefit using a special eye care or cleansing products. Yes, there is!
As I mention in many of my previous posts, the right pH-level is very important for healthy skin. Skin usually prefers a pH of around 5. However there are some area's where the skin's natural pH balance is a little bit different. One of those area's is the area around the eyes. The preferred pH-level there is around 7, thus less acidic and more alkalic in comparison to your regular cleansing or care product for face or body. This is one of the most important reasons why I would recommend to use a special eye make-up remover and eye care product, as they are adjusted to the pH level most suitable for use in the eye area. Furthermore, special eye products are tested and proven to be safe when used around the eyes, while it isn't always recommended or proven for a regular face product. Some care products have a tendency to "travel" or migrate into the eye area. Even when not directly applied around the eyes, they might end up there. A special eye care product can form a "barrier" and thus help to prevent that unwanted products move to the eye area and cause irritation. I would particularly recommend the use of an eye cream when using other products containing gold standard anti-ageing active ingredients like Vitamin A, C (or derivatives of both), Hydroxy Acids (Alpha, Beta or Poly), when you have experienced some sensitivity of the eyes or eye area in the past or have a more problematic skin type. Eye care products preferably should not contain Vitamin C (L-Asorbic Acid or related) as it requires a low pH value of <4 to be active and do it's job properly. Eye care products with Vitamin C therewith are either too acidic to be used in the eye area or alternatively too alkalic for the Vitamin C to be effective. Safe to use in the eye area are products containing Hyaluronic Acid. Although "Acid" is in the name, Hyaluronic Acid isn't acidic. One of it's key functions is attract and bind water, which usually has a pH of ~7. Take care! 7/22/2018 Comments Chemical or mechanical exfoliation
We can support's skin natural exfoliation process in various ways, for example with mechanical or chemical exfoliation.
Desquamation (shedding of skin cells thus exfoliation) is an important part of the skin's natural regeneration or renewal process. Already in our twenties, this process slightly, however increasingly starts to slow down (Kligman 1983). As a result, the cells on the surface of our skin (corneocytes) become bigger (Kligman 1989) and a little disorganised. This leads to a duller appearance (loss of radiance) and a more rough texture of our skin. A very comprehensive comparison of both methods:
The word "acid" unfortunately sounds very harsh and skin-unfriendly. Many acids are actually skin's own, like for example lactic acid is a skin's own natural moisturising factor (NMF) and so is hyaluronic acid. The level of NMF's decrease as we age and our skin my lose the ability to maintain well hydrated. Many years ago the benefits of lactic acid were capitalised by using baths filled with donkey milk. Citric acid is commonly used in skin care products and toners to balance skin's pH. Gluconolactone is only gradually penetrates skin and is very gentle.
It's unfortunate that "acids" have such a negative connotation, as our skin (healthy and problematic) can benefit if we use them regularly. Moreover, I prefer this method over mechanical exfoliation for all skin types, however particularly if you have dry skin, acne- or redness prone skin, sensitive skin or mature skin. The risk of exfoliation is over-exfoliation. Over-exfoliation is damage of our skin barrier and the symptoms are very comparable to dry or (hyper) sensitive skin symptoms, which are: redness, irritation, tightness, excessive dryness, dry patches, flaking skin, uncomfortable stinging, or even burning sensation. Whenever you experience one or more symptoms of over-exfoliation, it's recommended to reduce the number of times you exfoliate and support the skin barrier repair with a moisturiser. Hope you enjoy healthy skin & take care. 7/12/2018 Comments Relation skin pH and ageing process
A high pH value contributes to premature ageing skin!
A study published in British Journal of Dermatology showed that women with an alkaline stratum corneum (outer layer of the skin) developed more fine lines and crow's-feet (wrinkles at the outside corner of the eyes) than those with acidic skin over an eight-year period. This might be in part because an alkaline epidermis (top layer of the skin) tends to be drier and more fragile than an acidic one. Irritants can enter the skin and water can evaporate more easily. People with hydrated skin showed a 50% lower rate of wrinkling than those with dry skin. If the acid mantle is not intact, it can make skin more susceptible to inflammation (inflammaging) and lowered enzymatic activity, which again increases the risk of development of signs of ageing. Last but not least, alkaline skin is more prone to sun damage thus photo-aging, because its protective barrier has been weakened. pH balance is fragile. I just mentioned that alkaline skin tends to be drier, however it’s also known that the oils secreted by our skin impact skin’s pH by increasing it. This is one of the reasons that oily skin types can be more prone to acne, as the skin’s pH influences it's microflora. That's a topic for another blog post. You’ve maybe seen some of my previous posts on skin’s pH and it’s actually one of my major topics. This is because healthy skin starts with an optimal pH balance. Click below in the featured categories on “Skin pH” if you like to learn more about pH. If there is a specific topic you are interested in missing, please place a comment below and I will see to it that I address it. Take care. 7/10/2018 Comments Facial toners redundant?
Recently I've read an article in which facial toners were called a redundant step in the cleansing routine. They would not serve any purpose anymore and would be “old-fashioned". I disagree, and will explain why.
Particularly when you prefer wet facial cleansing (water has a pH of 7-8), your skin’s pH goes up and you may consider using a toner to bring it back to normal (~5) before using a moisturizer or serum. This also applies if you use an alkaline cleanser or micellar water. It is common that products which are suitable to be used around the eyes, like micellar water, are adapted to a more “eye-friendly” and less “skin friendly” pH of ~7. Skin prefers a pH of ~5. In my humble opinion, toners are a very important step in every a.m. and p.m. skin care regimen for both healthy and particularly problematic skin types. They refresh, remove left-over debris and make-up and moreover instantly rebalance skin’s pH value. A balanced pH value is the cornerstone for healthy skin. An optimal pH supports skin's microbiome (microflora or "ecosystem") and barrier function. Furthermore, the use of a toner usually helps the penetration and thus efficacy of your care product! Alternatively, you can use “chemical” exfoliating lotions or pads which contain AHA (glycol, citric and lactic acid), BHA (salicylic acid), PHA (gluconotactone), etcetera. Just be careful using them around the eyes or even avoid this area. Hope you enjoy healthy skin & take care. 7/8/2018 Comments Wellness not skin friendly?
Long showers and bathing, though considered wellness or “home spa” experience, may actually cause a major disruption to our skin’s pH and skin barrier. The same goes for swimming (in salty sea or pool with chlorine).
These activities increase the risk of skin sensitivity and dryness. Water has a pH of 7-8 while our skin’s optimal pH balance requires a pH ~5. To make long showers and bathing a more a skin friendly experience, it is highly recommended to use non-alkaline or slightly acidic gentle cleansers (preferably with a pH ~5). If you have time, apply afterwards a pH rebalancing body lotion or butter. Your skin will surely appreciate it. I would personally never even consider applying an alkaline body product, as it might take the skin several hours to rebalance it’s pH on a large surface. Instead of hydrating your skin, you may in fact increase the risk of water loss; which is a waste of precious time and (expensive) product. Surely, I don't want to discourage anybody from enjoying swimming, relaxing long showers and baths! Just give your skin a "little love" afterwards. 
Although I am writing this blog post as a private person, the skin care company I am working for as a senior global medical manager was one of the first, if not the first to understand the importance of optimal pH balance of the skin, the cornerstone for healthy skin of face and body. Every day, we expose our skin to pH disruptors, like water (usually a pH of 7-8), alkaline soap, sun, pollution and many more. Even though our skin is resilient and eventually will go back to it’s optimal pH (»5), it is common sense and beneficial for our skin’s health to support our skin with a suitable skin care regimen, reducing disruption and promoting pH-balance.
WHAT IS pH? pH literally means the power (or concentration) of hydrogen atoms in a substance. Substances with a higher concentration of Hydrogen atoms than Hydroxide molecules have a greater acidic 'power' (acids), while those with lower H+ (Hydrogen) and higher OH- (Hydroxide) concentrations have less acidic power (bases). The pH scale runs from 0 to 14: 7 is a neutral pH, values below 7 (6-0) are increasingly acidic while values above 7 (8-14) are increasingly basic. There is a 10-fold difference in concentration between these values, meaning that pH 0 is 10 times stronger than pH 1, 100 times stronger than pH 2, and 10,000,000 times stronger than pH 7. With other words; a slight increase in pH, can make a big difference for your skin. SOME PHYSIOLOGICAL FUNCTIONS OF SKIN pH
SKIN BARRIER pH plays a fundamental role in the skin's barrier, acid mantle or buffer, which is formed by secretions from sweat and sebaceous glands as well as the breakdown of fatty acids by beneficial micro-flora. The barrier functions like an invisible protective veil (hydrolipid film) that protects skin’s lipids, moisture loss and unwanted allergens, pollution and bacteria. The acid mantle is at its strongest and most optimal balanced when the skin is slightly acidic, with an average pH of about 5.5 (ranging anywhere from 4.5 to 6.2). However, different areas of the body have slightly different requirements and different optimal pH ranges. The skin of women is slightly more acidic than skin of men. pH BIORYTHM Skin surface pH decreases during normal working hours with maximum values in the afternoon and minimum values during night time. You’ve probably heard that our skin regeneration is most optimal during night time? Indeed, our skin’s pH plays a key role in this too. In separate posts I will address various specific skin pH related topics, as I could go on forever about pH. There is so much to share on this topic (and still to discover) and balanced pH is essential for healthy skin, from cradle to grave, for all skin types & all phototypes. Please check out my other posts, if you are interested. Hope you enjoy healthy skin & take care. 7/7/2018 Comments Skin's pH influences hydration
Our skin’s pH plays an important role in many processes influencing skin hydration.
Increased pH (more alkaline >6) values correspond with an increase in trans-epidermal water loss, which we refer to in studies as TEWL, one of the most significant indicators of a good epidermal barrier function. The epidermal barrier protects our skin against (excessive) loss of water and thus protects the maintenance of correct hydration. The skin pH promotes the correct organization of the matrix lipids too, by regulating their surface structure and stability. All leading up to better hydrated skin. It makes sense to pay attention to pH when buying your cleansing and care products. Hope you enjoy healthy skin & take care. 2/27/2018 Comments Malodorous armpits
Ever wondered why armpits are smelly, even when using a luxurious and fabulous fragranced deodorant?
The answer might be in your skin’s pH value. Sweat secreted by the glands under our armpits increases local skin’s pH value. This negatively influences it’s microflora, also called skin’s microbiome. A high and unhealthy pH value encourages certain odor-producing bacteria to flourish. Hence, a more alkaline (high) pH value due to (excessive) sweat, does cause smelly armpits or other malodour in other body areas. No fragrance can mask or does counteract this process effectively. That's why we can still suffer from smells armpits while using deodorant. What you can do to balance pH and keep armpits dry Opt for a skin pH friendly deodorant (~5) which reduces perspiration. With less sweat and by maintaining skin’s optimal pH balance, you will automatically reduce nasty bacterial activity. Keep armpits clean Regularly wash away the alkalising sweat and bad bacteria with their smelly by-products. Some skin experts recommend using antibacterial soap. It will reduce all bacterial activity, good and bad. I would rather target only the unwanted bacterial activity with a more skin-flora friendly approach by using gentle cleansing products with a pH value ~ 5. This keeps good bacteria on the skin (we need them for balance) and discourages growth of overly active odor producing bacteria. Make sure that your armpits dry down properly before and after applying a thin layer of deodorant. Shaving Reserve shaving armpits or the use of other hair removal devices for night-time. Gently cleanse and dry your skin prior. Removing hair in the evening and postpone using a deodorant till the next morning will allow your skin to recover a few hours. Mild abrasive hair removal methods can cause micro-injuries to the skin barrier which makes our skin more prone to irritation. Anyway, most of us are less bothered by odor, or at least less aware while sleeping, and we depend more on our pH friendly deodorant to do a good job during day time. Use all skin care products with modesty, except sunscreen! Hope you will enjoy a great summer without malodorous armpits. |
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