All you need to know about oxidative stress and its effects on the skin.

Oxidative stress refers to an imbalance between the production of free radicals, whether reactive oxygen species (ROS) or reactive nitrogen species (RNS), and the skin’s ability to defend itself. Under normal conditions, these molecules play physiological roles in cellular signaling, immune defense, and wound healing. However, when their production exceeds the body’s antioxidant capacity, they become toxic to skin cells and impair their proper functioning.

Free radicals are extremely unstable molecules possessing one or more unpaired electrons in their outer shell. Under normal conditions, electrons occur in pairs, ensuring energetic balance. When an electron is unpaired, the molecule seeks to restore stability by capturing or donating an electron from another molecule. This drives free radicals to react with their surroundings, particularly lipids, proteins, and the DNA of skin cells, resulting in structural and functional alterations.

To prevent such damage, the skin possesses an endogenous antioxidant system comprising enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase, as well as non-enzymatic antioxidants such as vitamin E, vitamin C, glutathione, and coenzyme Q10. These antioxidants serve as a defensive shield and neutralize free radicals before they can react with cellular components. However, when this shield is overwhelmed due to an overproduction of free radicals or a failure of the antioxidant system, the redox balance shifts, resulting in a state of oxidative stress.

Oxidative stress in the skin results from an combination of internal and external factors. Internal factors arise from the body's normal functioning and metabolic processes, while external factors are linked to environmental and lifestyle influences. Thus, free radicals naturally accumulate in the skin, but certain habits can increase their numbers and amplify their effects.

An internal production of free radicals via metabolism.

The production of free radicals in the skin largely arises from internal mechanisms, notably cellular metabolic processes. Mitochondria represent a major source of reactive oxygen species, generated as byproducts of normal metabolism via the respiratory chain. The superoxide ion (O2•-), initially produced in the mitochondrial matrix, intermembrane space, and outer membrane, can be converted into hydrogen peroxide (H2O2) by the action of superoxide dismutase (SOD) or react with nitric oxide (NO•) to form peroxynitrite (ONOO−), a particularly reactive RNS.

Beyond mitochondria, several intracellular enzymes contribute to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS): NADPH oxidases, xanthine oxidoreductase, certain peroxisomal oxidases, cytochrome P450 enzymes, cyclooxygenases, and lipoxygenases. These enzymes often depend on iron and its derivatives, such as heme or iron–sulfur clusters, to function properly. A phenomenon known as “ROS-induced ROS release” (RIRR) can occur when the ROS generated stimulate the formation of new ROS via the opening of the mitochondrial permeability transition pore, thereby amplifying intracellular oxidative stress.

The normal metabolism of the skin, necessary for its survival and renewal, is a constant source of free radicals.

An imbalance in the skin microbiota can lead to oxidative stress.

Human skin harbors a complex and dynamic community of microorganisms, the cutaneous microbiota, which plays a crucial role in maintaining the skin’s barrier function, its immunity, and in preventing certain dermatoses. Indeed, alterations of the skin microbiota have been associated with conditions such as psoriasis, eczema, or acne, underscoring the importance of protecting it. However, the balance of the microbiota can be disrupted by environmental factors such as UV exposure or organic pollutants like polycyclic aromatic hydrocarbons, which induce oxidative stress in the skin.

The skin microbiota also influences the balance of oxidative stress via through interactions with the gut microbiota as part of the gut-skin axis. Disturbances in the skin flora can promote the accumulation of free radicals as well as inflammation. Several studies have shown a correlation between the severity of certain skin diseases partly due to an imbalance of the skin microbiota and blood oxidative stress markers, such as malondialdehyde and NO. These findings suggest that maintaining a balanced microbiota is essential for regulating skin oxidative stress.

A study conducted on 25 patients with atopic dermatitis and 25 healthy subjects helped illustrate this link. The researchers assessed levels of malondialdehyde (MDA), a marker of oxidative stress, along with enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione, vitamins A, E, and C) in both the patient group and the healthy controls. The results revealed that eczema patients exhibited a significant increase in MDA, accompanied by a pronounced decrease in antioxidant levels. These findings indicate an increased vulnerability to free radicals. In eczema—where the skin microbiome is imbalanced with elevated Staphylococcus populations and the skin barrier is compromised—this oxidative stress contributes to the persistence of chronic inflammation and tissue damage.

Exposure to UV rays, visible light, and infrared radiation contributes to oxidative stress.

Ultraviolet rays are the primary external source of free radical production within the skin. Under solar exposure, photons from UVA radiation (320–400 nm) and, to a lesser extent, UVB radiation (280–320 nm) are absorbed by endogenous photosensitizing molecules such as cytochromes, riboflavin, heme, or porphyrin. Once excited, these molecules react with oxygen to generate various reactive oxygen species, notably the superoxide anion (O2•-) and singlet oxygen (¹O2).

These free radicals then trigger a cascade of deleterious chemical reactions : superoxide is converted by superoxide dismutase (SOD) into hydrogen peroxide, a molecule capable of diffusing across cellular membranes. In the presence of transition metals such as iron (Fe2+) or copper (Cu2+), H2O2 then generates the hydroxyl radical, one of the most toxic for skin cells. This process contributes to lipid peroxidation, the alteration of structural proteins such as collagen and elastin and to DNA damage.

In addition to UV radiation, visible light (400–700 nm) and infrared radiation (700–4000 nm) also contribute to the formation of reactive oxygen species (ROS) in the skin. Visible light can generate hydroxyl radicals (•OH), hydroperoxyl radicals (•OOH), and singlet oxygen, intensifying oxidative stress. Infrared light, in turn, acts primarily at the mitochondrial level, where it stimulates the production of ROS that are then converted into heat, notably activating heat shock protein MP-1. These mechanisms contribute to the progressive deterioration of the skin barrier and promote the onset of oxidative stress.

Pollution has oxidative effects on the skin.

Daily exposure to air pollution is another significant external source of oxidative stress for the skin. Fine particles from fuel combustion contain polycyclic aromatic hydrocarbons. These highly photo-reactive molecules are activated by UV radiation, triggering a massive production of reactive oxygen species. This synergy between pollutants and solar radiation considerably amplifies oxidative stress.

Nitrogen oxides (NO and NO₂), primarily emitted by road traffic and solid fuel combustion, also contribute to this oxidation. By reacting with the skin’s photoactivated chromophores, these gases facilitate the formation of superoxide radicals and nitrated radicals, which damage the lipids and proteins of the hydrolipidic film. This repeated oxidation gradually erodes the skin’s protective barrier, making it more permeable and reactive.

Another major pollutant, ozone (O₃), perfectly illustrates the complexity of oxidative stress in the skin. Although it does not penetrate into the skin, it acts on the surface, where it rapidly reacts with sebum to form lipid peroxidation products and reactive aldehydes. These pro-oxidant compounds trigger local inflammation and accelerate the depletion of essential antioxidant vitamins in the skin, such as vitamin E and vitamin C.

Smoking, a direct source of oxidative stress.

Smoking is a potent external factor in the generation of cutaneous oxidative stress. Cigarette smoke contains more than 4,000 chemical compounds, including a large proportion of free radicals and oxidizing agents. These reactive species, such as nitric oxide (NO•) and the peroxynitrite radical (ONOO–), penetrate the skin directly from inhaled air or through epidermal contact. They trigger an oxidation cascade that destabilizes the lipids of the cell membrane and depletes the skin’s antioxidants, thus impairing its ability to defend against ROS. At the same time, tobacco disrupts cutaneous microcirculation, which reduces the supply of oxygen and nutrients to cells, a process that promotes the internal production of superoxide radicals (O2•–).

Diet can influence oxidative stress.

Diet, notably sugar consumption, directly affects oxidative stress in the body. When glucose is present in the blood at excessively high levels, it reacts spontaneously with proteins, lipids, or nucleic acids to form advanced glycation end products (AGEs). This process, known as glycation, impairs the structure and function of skin proteins—particularly collagen and elastin—making the skin stiffer and less resilient. AGEs also promote the production of free radicals such as superoxide (O₂•⁻) and peroxynitrite (ONOO⁻), further amplifying oxidative stress within the skin.

Moreover, the formation of AGEs is accompanied by an activation of the transmembrane receptor RAGE (Receptor for Advanced Glycation End Products), present in keratinocytes and fibroblasts. Its activation stimulates the release of proinflammatory cytokines and increases mitochondrial ROS production, creating an oxidative and inflammatory vicious cycle. Conversely, a diet rich in natural antioxidants—especially from fruits, vegetables, nuts, and polyphenol-rich oils—helps neutralize free radicals and limit glycation.

Psychological stress, a driver of oxidative stress.

Chronic psychological stress is an often underestimated internal factor in the development of cutaneous oxidative stress. Once established, it simultaneously activates the autonomic nervous system, the renin–angiotensin system, and the hypothalamic–pituitary–adrenal axis. These mechanisms lead to the release of angiotensin II, a molecule capable of stimulating the production of NADPH oxidase–dependent ROS within neutrophils. At the same time, angiotensin II inhibits the synthesis of heme oxygenase-1, an antioxidant enzyme, thereby reducing the cells’ ability to defend against oxidation.

Moreover, several studies have highlighted a link between depressive disorders and an increased oxidative state. For example, the work conducted by Gibson and his team involved 32 individuals, 16 of whom suffered from depression. The researchers demonstrated that fibroblasts from depressed patients exhibit elevated protein carbonylation and overexpression of glutathione reductase, markers of heightened cellular oxidative stress.

Oxidative stress has multiple effects on skin physiology. Indeed, free radicals disrupt cellular structures, proteins, lipids, and DNA and trigger inflammatory responses. These disturbances manifest as visible and functional changes in the skin, notably skin laxity, pigmentation disorders, and a weakened skin barrier function.

Oxidative stress accelerates the loss of skin elasticity.

Oxidative stress directly affects collagen and elastin fibers, essential components of the dermal structure. Free radicals oxidize these proteins, leading to their fragmentation and a reduction in their ability to maintain the skin’s firmness and elasticity. Moreover, ROS activate enzymes such as matrix metalloproteinases (MMPs), which further degrade collagen and elastin, accelerating skin laxity and the appearance of wrinkles.

Simultaneously, oxidative stress disrupts the functioning of fibroblasts, the cells that synthesize collagen, elastin, and glycosaminoglycans such as hyaluronic acid. Fibroblasts exposed to reactive oxygen species (ROS) exhibit reduced proliferation and activity, limiting their dermal regenerative capacity. This combination of enzymatic degradation and decreased cellular production leads to a gradual loss of skin density and firmness, promoting premature skin aging.

Oxidative stress can cause pigmentation disorders.

Oxidative stress strongly influences skin pigmentation, notably through the action of free radicals on melanocytes, the skin cells that produce melanin. The mechanisms regulating pigmentation are complex, but it is now established that UV exposure and the resulting oxidative DNA damage induce cellular signals that stimulate the melanogenesis. Nitrogen radicals, particularly nitric oxide (NO•), are notably involved. NO produced by UV-exposed keratinocytes stimulates the α-MSH/MC1R pathway, activating tyrosinase, the key enzyme in melanin synthesis. ROS, such as H2O2, also play a role in regulating tyrosinase via activation of proteins like MITF and signaling pathways such as ERK and JNK.

Oxidative stress acts as a genuine intracellular messenger, triggering melanin production and accentuating the appearance of pigmentary imbalances.

Oxidative stress weakens the skin barrier.

Oxidative stress affects the integrity of the skin barrier, which is essential for protecting the skin against environmental insults and minimizing water loss. ROS and RNS can oxidize lipids in the stratum corneum, leading to a loss of corneocyte cohesion and an alteration of intercellular lipids. This process weakens the skin barrier and increases transepidermal water loss, which can result in skin dehydration.

At the same time, oxidative stress can disrupt the synthesis of structural proteins, such as filaggrins and loricrins that help maintain the skin barrier. The buildup of free radicals also triggers localized inflammatory responses via the activation of pro-inflammatory cytokines, which amplifies barrier dysfunction and contributes to the onset of irritation and redness.

Note : By altering the DNA and mitochondrial activity of keratinocytes, oxidative stress can impair their ability to proliferate and cause a slowdown in cellular turnover. This manifests as an accumulation of dead cells on the surface of the epidermis that can prevent light from reflecting properly, giving the skin a dull appearance.

To combat oxidative stress, the balance between antioxidants and free radicals must be restored by an external supply of antioxidants.

Indeed, antioxidants neutralize free radicals and thus limit the oxidation of lipids, proteins, and DNA. Among the most studied antioxidants for the skin are vitamin C, vitamin E, beta-carotene, and selenium, found in fruits, vegetables, nuts, and fatty fish. The vitamin C, for example, participates in collagen synthesis while protecting cells against ROS. The vitamin E, being fat-soluble, acts primarily at the cellular membranes, limiting lipid peroxidation and stabilizing the skin barrier. A varied diet, rich in berries, citrus fruits, green vegetables, and nuts, therefore supports the skin’s natural defense against oxidative stress.

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

Alongside diet, antioxidant-enriched cosmetics are effective tools for protecting the skin. Serums containing stabilized vitamin C, of the resveratrol or the coenzyme Q10 act by reducing the accumulation of free radicals in the skin. At the same time, it is essential to protect the skin daily from UV rays, which generate oxidative stress and are the primary cause of skin aging.

Finally, a balanced lifestyle (avoiding tobacco use, practicing sun protection measures, managing psychological stress, etc.) helps limit oxidative stress.

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