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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
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
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=10]. 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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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)
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Blue light, is also known as high-energy visible (HEV) light and is the most energetic part of the visible light spectrum (380 - 700 nm) with wavelengths ranging from indigo or ultramarine light 420-440 nanometers, blue light 450-495 nanometers to cyan light 480 - 520 nanometers. Blue light has lower energy than ultraviolet (UV) radiation (280–400 nm) and can reach further into the dermis, up to the depth of 1 mm. [1] Sunlight is the primary natural source of blue light. Up to 50% of the damaging oxidative stress in human skin is generated in the VIS spectrum and the other 50% by UV light [2], contributing to premature ageing, ox-inflammageing and hyperpigmentation like age spots.
Blue light from electronic devices The use of electronic devices has led to increased exposure to artificial blue light sources, however the amount of blue light emitted during the conventional use of electronic devices is by far not enough to trigger harmful skin effects. If you sit in front of a monitor uninterrupted for a week at a distance from the screen of approximately 30 cm, this would be the same as the blue light intensity of spending one minute outside on a sunny day in Hamburg Germany at around midday at midsummer. If you hold a smartphone right next to the skin, the intensity does increase, but it would still take approximately 10 hours of uninterrupted use to match the effect on the skin of just one minute of sunlight. The emissions from electronic devices are barely noticeable in comparison to natural blue light directly from the sun and are, thus negligible. However, blue light or HEV light from sunlight can be harmful for skin. Dr Ludger Kolbe Chief Scientist for Photobiology and his team at Beiersdorf AG did pioneering research regarding the harmful effects of HEVIS. [3-4] I would also like to take the opportunity to debunk an important myth at the start of this article as infrared or near infrared light does not induce damaging free radicals (even in high amounts), there is no such thing "infra-ageing" as a result or IR and in fact red light photobiomodulation supports skin rejuvenation. Read more Direct effects of blue light and HEV Light on skin Blue light and HEV light can have both beneficial and detrimental effects on the skin. The most significant direct effects are mediated through their interaction with chromophores, such as flavins, porphyrins, and opsins, which can trigger the overproduction of reactive oxygen species (ROS), reactive nitrogen species (RNS). and hyperpigmentation. Reactive oxygen and nitrogen species cause DNA damage and modulate the immune response. [1] This oxidative stress can lead to: Photo-ageing: Exposure to blue light and HEV light can induce premature skin aging, causing wrinkles, fine lines, and loss of elasticity. Hyperpigmentation: Blue light and HEV light can stimulate melanin production, leading to uneven skin tone and the development of age spots or other forms of hyperpigmentation. DNA damage: The ROS and RNS generated by blue light and HEV light can cause DNA damage, plus potentially increase the risk of skin cancer. Inflammation: The oxidative stress triggered by blue light and HEV light can cause an inflammatory response in the skin, exacerbating conditions like acne, eczema, and psoriasis. Molecular and physiological mechanisms of direct blue light effects on the skin [1]
Indirect effects of blue light and HEV Light on skin Blue light and HEV light can also have indirect effects on the skin by disrupting the body's circadian rhythms. This occurs via both the central mechanism, which involves stimulation of light-sensing receptors located in the retina, and via the peripheral mechanism, which involves direct interaction with skin cells. By disrupting the normal circadian rhythm, blue light can negatively affect the skin's natural overnight repair and regeneration processes. [1] The circadian rhythm has been shown to affect multiple cellular and physiological processes occurring in the skin:
Molecular mechanisms of indirect effects of blue light on the skin [1]
Ideal daytime & nighttime skin care regimen When considering cosmetic interventions, a strategy of daytime protection plus defense and night-time repair may be optimal. The skin's own repair mechanisms, such as base excision repair and nucleotide excision repair, attempt to mitigate blue light induced DNA damage. [12] Daytime protection plus defense Of course prevention and/or reduction of blue light exposure from sunlight is key. Reduce the time spent on electronic devices, especially before bedtime, can help minimize the disruption of circadian rhythms and the indirect effects of blue light and HEV light on the skin. Against premature ageing and hyperpigmentation an evidence based effective approach could be the daily use of tinted broadband sunscreen preferably containing Licochalcone A (the most effective anti-oxidant reducing damaging free radical activity from both UV and blue light and moreover protects against collagenase MMP-1 expression) strengthening skin's biological defense [4-5-6-7], while iron oxides in colour pigments provide physical protection against blue light (like zinc oxide and titanium dioxide). Against hyperpigmentation there are (tinted) sunscreens which on top contain the most potent human tyrosinase inhibitor found in dermatological skin care called Thiamidol® [8-9] and one of the 3 ingredients in the "new Kligman Trio" (NT) [18] and Glycyrrhetinic Acid which supports skin's DNA repair and skin pigmentation [10] and inhibits hyaluronidase activity (HYAL1). Most regular sun filters used in sunscreen don't offer any protection against blue light, however according to the website of BASF the chemical UV filters Tinosorb® A2B and Tinosorb® M can reduce the exposure to blue light. [11] Scattering and absorption of blue light [5] The penetration depth of visible light is influenced by the reflection, scattering, and absorption mediated not only by the skin’s physical barrier but also by the VL chromophores in the skin and Fitzpatrick skin or photo-type (FST). The primary VL-scatter and absorption molecules in the skin include hemoglobin, melanin, bilirubin, carotene, lipids, and other structures, including cell nuclei and filamentous proteins like keratin and collagen. Melanin and keratins are the primary VL absorbers and scatterers in the epidermis, while hemoglobin is the dominant absorber, and collagen is the major VL scatter in the dermis. Melanin's absorption spectrum ranges from 200 to 900 nm, with the peak absorption varying based on melanin moiety. This means that individuals with darker skin types, which have higher melanin content, are more prone to hyperpigmentation from blue light or VIS due to the greater absorption and scattering of VIS in their skin on top of the previously mentioned higher levels of tyrosinase–DCT complexes leading to increased melanogenesis, leading to both transient and long-lasting pigmentation [13], dependent upon the total dose and exacerbation of melasma especially in individuals with FSTs III to VI. Blue light tanning Recent data demonstrate synergistic effects between VL and UV-A on erythema and pigmentation. VL-induced pigmentation is more potent and more sustained than UVA1-induced pigmentation in darker skin tones.Typically, three mechanisms are involved in the responsive reaction of melanocytes to VL, with increased melanin content: immediate pigment darkening (IPD), persistent pigment darkening (PPD), and delayed tanning (DT). [15] Read more. VL can also exacerbate post inflammatory hyperpigmentation (study with FST IV and V). [16] Blue light therapy While the detrimental effects of blue light and HEV light on the skin have been well-documented, these wavelengths have also shown promise in the treatment of certain skin conditions. In controlled clinical settings, blue light has been used to: Treat Acne: Blue light can reduce the growth of Propionibacterium acnes, the bacteria responsible for acne, and has an anti-inflammatory effect. Manage Psoriasis and Atopic Dermatitis: Blue light has been found to have an anti-inflammatory and antiproliferative effect, making it potentially beneficial for the treatment of these chronic inflammatory skin diseases. Reduce Itch: Some studies have suggested that blue light may help alleviate the severity of itching in certain skin conditions. Vitiligo: Blue light therapy via LEDs can stimulate repigmentation in patients with vitiligo with minimal adverse events, however larger studies are needed. [17] The optimal protocols for blue light therapy are still being developed, and the long-term safety of this treatment modality requires further investigation and should not be initiated without HCP recommendation and monitoring. Overall, the research suggests that prolonged or excessive exposure to high-energy blue light, can have negative long-term effects on skin structure, function, and appearance in all phototypes. As our understanding of the individual variations in skin's response to blue light exposure deepens, the development of personalised or tailored effective solutions become increasingly more tangible. Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for your particular skin condition and rejuvenation goals. Take care! Anne-Marie
References
Many people associate a tan with health, beauty and an active lifestyle. Although a moderate dose of solar radiation is indispensable for our health, unfortunately, there is no such thing as a real "healthy tan" or "healthy sun-kissed glow" as it is always a visible sign of skin damage. Tanning is a response by the skin to exposure to ultraviolet (UV) radiation (and HEV or Blue Light), either from natural sunlight or artificial sources like tanning beds which leads to photo-ageing, pigmentary disorders (like age spots or hyperpigmentation) and immunosuppression, hence skin cancer. When skin is exposed to sunlight: UV rays and high energy visible light (HEV) or also called Blue Light (the most energetic region of HEV), it produces more melanin, a pigment that darkens the skin as a (partial) protective mechanism to prevent further damage. The amount of artificial blue light emitted during the conventional use of electronic devices is not enough to trigger harmful skin effects. (Click here to read more)
MELANIN Melanin is only produced by cells called melanocytes, mostly distributed in the epidermal-dermal junction. Melanocytes contain specialized organelles called melanosomes to store and produce melanin. Melanosomes are transferred from the melanocytes to the neighboring keratinocytes, which are the most abundant cells in the epidermis. One melanin-forming melanocyte surrounded by 36 keratinocytes and a Langerhans cell is called the melano-epidermal unit. [1.2] Melanocytes use the amino acid tyrosine to produce melanin and protect epidermal keratinocytes and dermal fibroblasts from the damaging effects of solar radiation.. [13] The are two melanin pigment classes:
Differences in skin pigmentation do not result from differences in the number of melanocytes in the skin, as one might assume, but from differences in the melanogenic activity (melano-competence), the type of melanin produced in melanosomes (the ratio between eumelanin and pheomelanin differs per Fitzpatrick phototype) and the size, number and packaging of melanosomes, with melanin content of melanosomes ranging from 17.9% to 72.3%. [7] The amount of melanin is never enough for adequate photoprotection, and a "base tan" does not prevent sunburn. Particularly darker phototypes are more sensitive for the damaging effects of Blue Light. Both eumelanin and pheomelanin production are promoted by UV radiation and Blue Light and therefore sunscreens offering a combination of both UV (A + B) protection and Blue Light defense are recommended for all phototypes. TANNING PROCESS The skin's tanning process occurs in four distinct phases: [3]
ROLE OF UVA, UVB AND BLUE LIGHT One of the most important acute effects of UVR is DNA damage. UVA and UVB show different properties regarding their biological effects on the skin. [7] Shorter wavelengths (nm) correspond to higher energy. Infrared does not induce oxidative stress. Read more UVA radiation (320-400 nm) penetrates deeper into the skin and can induce indirect DNA damage by the generation of reactive oxygen species (ROS), leading to premature skin aging. UVA, in contrast to UVB is not filtered by window glass, is able to penetrate deeper into the skin and reach the dermis. They are present constantly, with relatively equal intensity, during all daylight hours throughout the year. It has been estimated that 50% of exposure to UVA occurs in the shade. UVA rays are less intense than UVB, but there are 30 to 50 times more of them. To produce the same erythemal response, approximately 1000 times more UVA dose is needed compared with UVB. [7] The bulbs used in tanning beds emit mostly UVA. UVB radiation (280-320 nm) is less prevalent than UVA, primarily affects the outermost layers of the skin, causing direct DNA damage (more potent than UVA) and triggers inflammatory responses that lead to increased melanin production. UVB radiation fluctuates throughout the day, are at their strongest at noon. and are more cytotoxic and mutagenic than UVA. The action spectrum for UV-induced tanning and erythema are almost identical, but UVA is more efficient in inducing tanning whereas UVB is more efficient in inducing erythema (redness). Dark skin is twice as effective compared to light skin in inhibiting UVB radiation penetration. [7] UVB helps the skin to produce Vitamin D. Blue light (400-500 nm) visible light accounts for 50% of sunlight [11] and can contribute to immediate, delayed, continuous and long-lasting pigmentation by activating melanocyte-specific photoreceptors and increasing melanin synthesis, particularly in individuals with darker (melano-competent) skin types [9], cause DNA damage [10] and generate damaging reactive oxygen species in both the epidermis and the dermis. [12] The effects may last longer than those induced by UVA and UVB radiation. Blue Light can penetrate even deeper than UVA and reach the hypodermis. Blue light therapy is used to target acne causing bacteria and inflammation, however the risks might outweigh the benefits especially in darker phototypes and it might worsen acne marks. EPIDERMIS AND DERMIS Both dermal fibroblasts and epidermal keratinocytes play a crucial role in regulating skin pigmentation and tanning response. [13 15] In comparison to epidermal tanning, dermal tanning is less visible, however more immediate. Dermal fibroblasts secrete various paracrine factors that regulate melanocyte function, survival, and melanin production. Factors like hepatocyte growth factor (HGF), nerve growth factor (NGF), stem cell factor (SCF), and basic fibroblast growth factor (bFGF) stimulate melanogenesis and pigmentation [14 15] Fibroblast senescence and altered secretory profiles in conditions like melasma contribute to abnormal pigmentation by stimulating melanogenesis. [15] Epidermal keratinocytes produce factors like α-melanocyte stimulating hormone (α-MSH) and Wnt1 that activate melanogenic pathways in melanocytes, leading to increased melanin synthesis and transfer to keratinocytes. [15 16]. Keratinocyte-derived exosomes can enhance melanin production by melanocytes. [16] Differences in autophagic activity between various keratinocytes also influences pigmentation. [15] MicroRNAs MicroRNAs are small, non-coding RNA molecules that regulate gene expression by binding to messenger RNA (mRNA) and typically suppressing protein production, for example collagen. They are classified as epigenetic modulators. Several miRNAs have been identified as differentially expressed in aged skin compared to young skin, including: - miR-383, miR-145, miR-34a (upregulated in sun-exposed aged skin) - miR-6879, miR-3648, miR-663b (downregulated in sun-exposed aged skin) [17] Enjoy the sun, however protect your (and your children's) skin from a photo-damaging tan to remain skin health and beauty. Sunless self-tanning products containing dihydroxyacetone (DHA) or Erythrulose provide a safe alternative to achieve a "sun-kissed" glow. You can use after-sun skin care which helps to rehydrate, reduce damage of "sun-stressed" skin and support it's repair. Always consult a qualified healthcare professional or dermatologist to determine what the most suitable approach is for your particular skin condition and rejuvenation goals. Take care! Anne-Marie
References
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
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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 |
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