What are the causes of skin aging?

Skin aging results primarily from a series of internal processes programmed by our biology. These mechanisms, collectively referred to as intrinsic aging, occur naturally over time, independently of our environment. They reflect a progressive slowdown of essential cellular functions : epidermal renewal, collagen production, maintenance of hydration, antioxidant defense... This endogenous aging, encoded in our genes, gradually and inevitably alters the skin’s structure and physiology.

Genetic and cellular senescence.

Skin aging is first of all linked to cellular senescence, a gene-programmed process that leads to a gradual decline in the proliferation of skin cells. This loss results in thinning of the epidermis, decreased skin elasticity, and a reduced capacity to repair damaged tissue. Senescence was first described in 1961 by Hayflick and Moorhead, who demonstrated that somatic cells irreversibly lose their ability to divide after a limited number of divisions. This limit is largely due to progressive shortening of telomeres, the ends of chromosomes, which, when they become too short, activate a DNA repair signal leading to cell cycle arrest.

Senescent cells, while incapable of dividing, remain metabolically active and adopt a distinct phenotypic profile, termed Senescence-Associated Secretory Phenotype (SASP). This phenotype is characterized by the release of pro-inflammatory cytokines, growth factors, metalloproteinases, and other bioactive molecules that, over time, degrade the extracellular matrix, impair the function of neighboring cells, and drive chronic inflammation, a phenomenon also known as inflamm'aging. Senescent cells gradually accumulate in the skin, hastening the appearance of aging signs.

Oxidative stress.

The oxidative stress is a major factor in skin aging, resulting from an imbalance between the production of free radicals and the skin’s antioxidant defense mechanisms. With age, mitochondria become less efficient, producing more free radicals during cellular respiration, which damage cellular proteins, lipids, and DNA. Excess free radicals in the skin activate two senescent cell signaling pathways: the MAPK and NF-κB pathways. These pathways induce activation of the AP-1 complex, leading to increased TNF-α and matrix metalloproteinases (MMPs), enzymes capable of degrading the dermal extracellular matrix. In particular, AP-1 stimulates MMP1, MMP3, and MMP9, which fragment type I and III collagen into disorganized fibrils, reducing skin density and integrity.

The skin, however, possesses endogenous antioxidant systems to limit these effects. Among them, enzymes—such as superoxide dismutase and catalase—neutralize free radicals, while non-enzymatic antioxidants, such as glutathione, coenzyme Q10, vitamin C, and vitamin E, protect skin proteins and lipids and contribute to collagen synthesis and stabilization. Nevertheless, with age, the effectiveness of these defenses declines : for example, catalase activity in aged dermis is reduced, leading to hydrogen peroxide accumulation, and vitamin C and E levels drop, rendering the skin more vulnerable to external stressors.

Hormonal fluctuations.

Skin aging is also influenced by hormonal fluctuations, notably the decrease in estrogens. In women, menopause marks a sudden drop in estradiol production, a hormone until then synthesized by the ovaries. Estrogen acts on keratinocytes, fibroblasts, melanocytes, hair follicles, and sebaceous glands, thereby contributing to skin hydration, elasticity, and wound healing. This hormonal deficiency leads to a progressive atrophy of the cutaneous tissue, observable through skin thinning, a loss of collagen, reduced vascularization, and increased dryness.

Fibroblasts, less stimulated, produce less type I and III collagen, while elastic fibers become more disorganized. Indeed, estrogens act by binding to the nuclear ERα and ERβ receptors, which activate the transcription of genes involved in the production of collagen and dermal regeneration. Their deficiency alters the expression of these genes and simultaneously promotes the activation of matrix metalloproteinases, which are responsible for the breakdown of supporting fibers. This imbalance between collagen synthesis and degradation accelerates skin laxity and the formation of wrinkles.

But estrogens are not the only hormones involved. With age, the production of dehydroepiandrosterone (DHEA), a hormone secreted by the adrenal cortex, also declines. DHEA contributes to the peripheral synthesis of estrogens and androgens, serving as a hormonal precursor for the skin. It stimulates dermal fibroblast proliferation, promotes sebum production, improves skin hydration, and supports barrier function. Therefore, the decline in DHEA exacerbates the skin’s intrinsic aging.

Impairment of the skin barrier and immune function.

Intrinsic skin aging is not limited to a decline in metabolic or hormonal functions. It is also accompanied by a progressive disorganization of the skin barrier and an impairment of the immune mechanisms that defend it. Long regarded as a passive target of circulating inflammatory mediators, the skin is now recognized as a triggering organ of inflammation. Langerhans cells, the immune sentinels, detect danger signals and activate T lymphocytes, while keratinocytes themselves secrete cytokines such as IL-1, TNF-α, or GM-CSF.

However, when the epidermal barrier is disrupted, these cytokines rapidly increase, leading to epidermal hyperplasia and local inflammation. This phenomenon, beneficial in the case of a single assault, becomes harmful when it recurs over time. The continuous activation of lymphocytes and the release of pro-inflammatory mediators then sustain a vicious cycle of inflammation and tissue degradation, the inflammation disrupting keratinocyte differentiation.

Stem cell exhaustion.

Skin aging is accompanied by a progressive decline in the reservoir of epidermal and dermal stem cells, which are nonetheless essential for skin renewal. They ensure the continuous replacement of keratinocytes and tissue repair after injury. With age, their proliferation and differentiation capacity deteriorates. Several mechanisms explain this depletion: accumulated DNA damage, telomere erosion, and increased oxidative stress disrupt these cells’ genetic and metabolic stability. At the same time, reduced growth signals such as Wnt and chronic inflammation impair the stem cells’ ability to reactivate when the skin is injured.

Alteration of proteostasis.

Maintaining proteostasis—that is, the balance between protein synthesis, folding, repair, and degradation—is vital for cellular health. In young skin, a complex network of molecular chaperones, proteasomes, and autophagic systems ensures the continuous surveillance of damaged or misfolded proteins. However, with age, this organization becomes dysregulated, particularly under oxidative stress, leading to an accumulation of oxidized or denatured proteins within keratinocytes and fibroblasts. This triggers a low-grade inflammatory response and endoplasmic reticulum stress, resulting in increased apoptosis and decreased cell viability. Ultimately, the skin loses its suppleness, density, and regenerative capacity.

Intrinsic skin aging results from a series of interconnected biological processes: increased oxidative stress, hormonal alterations, immune system weakening, cellular exhaustion, and proteostatic imbalance. These mechanisms operate slowly yet inevitably, undermining the skin’s ability to regenerate and maintain its structural integrity.

In addition to the internal mechanisms described previously, the skin is exposed to several external factors that accelerate its aging.

Ultraviolet rays.

The harmful effects of the sun on the skin and its role in skin aging, referred to as photoaging in this specific case, are beyond question. Chronic exposure to ultraviolet (UVA and UVB) rays is one of the main factors accelerating skin aging. UVB rays, which are primarily absorbed in the epidermis, cause genotoxic damage by altering cellular DNA, disrupting collagen fiber organization and leading to its degradation. The more penetrating UVA rays reach the dermis and stimulate the expression of matrix metalloproteinases, weakening the dermal structure and contributing to skin laxity.

Meanwhile, UV radiation induces an excessive generation of free radicals, heightening oxidative stress that progressively accumulates over time. This imbalance fosters the emergence of telangiectasias, stiffening of the blood vessels, and the formation of pigmented spots. In individuals with fair skin or genetic variations—such as mutations of the MC1R receptor—free radical production is amplified, increasing the skin’s susceptibility to oxidative stress and accelerating photoaging.

Pollution.

Chronic exposure to air pollution is a major contributor to extrinsic skin aging. Environmental pollutants, such as hydrocarbons, oxides, fine particulate matter, and ozone, induce significant oxidative stress. Ozone, in particular, causes oxidative damage at the level of the stratum corneum and depletes both enzymatic and non-enzymatic antioxidant reserves—particularly vitamins C and E—while impairing mitochondrial function and reducing the production of ATP and sirtuin 3, which is essential for free radical elimination. Pollutant exposure also disrupts the skin barrier and compromises immunity, thereby promoting skin aging.

Tobacco.

In addition to making the complexion dull, the tobacco is associated with accelerated skin aging. Indeed, the components of cigarette smoke promote oxidative stress and chronic inflammation. These substances stimulate the production of matrix metalloproteinases, leading to the degradation of the collagen and elastin of the dermis. Tobacco also reduces skin vascularization, resulting in decreased oxygen and nutrient supply to the tissues. Furthermore, smoking impairs the function of keratinocytes and fibroblasts, compromising the skin’s ability to repair itself and maintain hydration.

FIROOZ and his team investigated the skin characteristics of smokers and non‐smokers. To accomplish this, 52 participants were evaluated to measure the elasticity, thickness, and density of their epidermis and dermis. The depth of the nasolabial folds—those creases running from the wings of the nose to the corners of the mouth—was also analyzed. The results showed that smokers displayed a reduced forehead elasticity, greater dermal thickness on the cheek, and lower epidermal density on the forehead as well as reduced dermal density on the arm. The tobacco is therefore a significant factor in skin aging.

Stress.

Stress, as with sleep deprivation, can impact skin aging. When the body perceives a threat, multiple physiological pathways are activated: the autonomic nervous system, the renin-angiotensin system, and the hypothalamic-pituitary-adrenal (HPA) axis. This activation triggers the release of stress hormones such as adrenaline, noradrenaline, and cortisol. In the short term, these mediators help the body adapt to acute danger. However, their prolonged stimulation plunges the organism into a state of metabolic and immune imbalance which increases the production of free radicals.

Studies have shown that catecholamines released during periods of stress can directly damage DNA and decrease the expression of the p53 protein, a key player in preserving genomic integrity. This decrease impairs the cells’ ability to repair their damage. Additionally, excess cortisol disrupts the skin barrier, reduces collagen production by fibroblasts, and promotes chronic inflammation — three processes closely linked to premature skin aging.

The lack of sleep, often occurring alongside stress, exacerbates these effects by intensifying inflammation. A study conducted by Kim and colleagues evaluated the effects of limiting sleep to four hours per night for six consecutive nights in 32 participants in their forties. The researchers measured skin elasticity (R2 parameter) and wrinkle depth (Ra parameter) around the eyes and forehead. Note that the closer R2 is to 1, the more elastic the skin. The results showed a progressive decrease in skin elasticity and a rapid increase in wrinkle depth as early as the first day of sleep deprivation.

A nutritionally imbalanced diet.

Nutrition can also play a role in skin aging. Diets rich in antioxidants help reduce oxidative stress and inflammation and promote collagen synthesis, thereby limiting the appearance of wrinkles, dryness, and skin atrophy. Conversely, diets high in fats, refined sugars, and trans fatty acids promote the formation of advanced glycation end products, which damage the skin’s structure and reduce its elasticity. An overly rich diet also has pro-inflammatory and oxidative effects on the skin. High-fat diets increase oxidative stress and reduce protein synthesis, resulting in less firm skin.

Good to know : The ORAC index (Oxygen Radical Absorbance Capacity) measures the antioxidant capacity of foods. The higher a food’s ORAC value, the stronger its antioxidant power.

Cutaneous aging is also due to external factors, which alter the skin's structural proteins, promote oxidative stress and inflammation, and accelerate tissue degradation.

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