Preventing skin aging: Epigenetics-targeted antioxidant in skincare
Oxidative stress and antioxidant interaction determine skin aging
Oxidant stress damage of the skin, as a fundamental factor of aging can occur early at birth and continue to the end of life. Skin oxidative damage results from an imbalance between Reaction oxidative species (ROS) generation and antioxidant defenses, of which unfavorable consequences include aging, increased skin diseases, loss of collagen and elastin, increased DNA damage, high skin sensitivity, and increased skin pigmentation. The symptoms could include: skin wrinkling, sagging, fine lines, loss of skin firmness, elasticity and glow, dehydration, etc. ROS includes hydrogen peroxide (H2O2), the superoxide anion radical (O2–), the hydroxyl radical (.OH), hypochlorous acid (HCLO), the nitric oxide radical (NO–) and the lipid peroxyl radical (LOO–). Skin ROS is mainly derived from ordinary metabolic reactions, cosmetics and a continuous exposure to oxidative environments such as UV irradiation from the sun.
The reduction/elimination of the intracellularly produced ROS depends on the removal by the antioxidant system. The antioxidant system consists of antioxidant enzymes and non-enzymatic antioxidants. Enzymatic antioxidants mainly include SOD, catalase and glutathione peroxidase. Their functions are to convert oxidized metabolic products in a multi-step process to H2O2 and then to water. Non-enzymatic antioxidants mainly include a) small exogenous (natural) molecules such as vitamin E, Vitamin C, Vitamin A, flavonoids, and carotenoids; and b) endogenous (physiological) organic molecules such as uric acid, melatonin, bilirubin and polyamines. The non-enzymatic antioxidant functions are to donate their electrons to scavenge for and to neutralize ROS.
Epigenetics regulation and control of skin aging
Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence – a change in phenotype without a change in genotype — which in turn affects how cells read the genes [ 1 ]. The epigenetic regulatory system mainly consists of DNA methylation, histone modification and chromatin remodeling. DNA methylation is mostly related to repression of gene expression through DNA methyltransferases and can be reversed to cause gene activation through DNA demethylase-directed demethylation process. Histone modification mainly includes histone methylation that may cause gene repression or activation, depending on the modified sites of the histones, and acetylation that generally results in gene activation. Chromatin remodeling refers to the dynamic modification of chromatin architecture, allowing transcription factors or other DNA binding proteins to access DNA to regulate gene expression.
Skin aging is hallmarked by the damaged macromolecular accumulations, impaired tissue renewal, and progressive loss of physiological integrity [ 2 ]. Skin aging can be classified into two different types: chronological aging, which is from the passage of time and is generally influenced by genetic or metabolic factors; and photo-aging, generally caused by environmental insults such as sun-exposure of the skin. Both chronological aging and photoaging can generate ROS and is accelerated by ROS. Accordingly, skin aging can also be slowed down by the reduction/elimination of ROS through the skin antioxidant system.
The epigenetically regulated expression of the anti-oxidative stress genes generates gene products- antioxidant protein/enzymes, which can scavenge ROS that arise from chemical, physical, and metabolic challenges. For example, methylation of these genes results in the gene inactivation and inability to produce antioxidant protein/enzymes accordingly. In contrast, demethylation of these genes causes gene activation to generate functional antioxidant protein/enzymes. The skin antioxidant system consists of 2 defense layers: Layer 1, skin epidermis: provide endogenous antioxidant action. As an initial barrier to oxidant assault, the epidermis contains up to 700% higher antioxidant enzyme activity (ex: catalase) and up to 900% higher non-enzymatic antioxidant activity (ex: Vitamin E) than the dermis [ 3 ]. These antioxidant components can be released from the keratinocytes of the epidermis to the skin surface. Layer 2, skin microbes: provide integral antioxidant action. There are approximate one million bacteria per cm2 in human skin. The skin microbiome is an integral part of the skin barrier that can affect skin health by modulating host immune responses and the skin barrier functions. Common bacteria on skin can secret antioxidant substances including RoxP to protect host skin from oxidative stress [ 4 ].
Epigenetics-targeted skincare antioxidants and their actions on preventing skin aging
In addition, antioxidant skincare products can also provide exogenous antioxidant action and may be considered as layer 3 of the skin antioxidant system when these products are applied to skin. Among skincare products, nearly 90% of these products are claimed to have antioxidant function. These products contain more or less antioxidant ingredients which mainly include non-enzymatic antioxidants: vitamin A, vitamin C, vitamin E, glutathione, carotenoids, and various plant polyphenols such as tea extracts. The antioxidant mechanisms and epigenetics-targeted action of these ingredients are listed in the following table.
Antioxidant mechanisms of epigenetics-targeted skincare antioxidants
The numerous evidences show that the epigenetics-targeted antioxidants are the most effective against oxidative stress damage of skin cell and tissues, and as consequence, significantly prevent or slowdown skin aging. It should be emphasized that skin status is dynamic, which is generated by interaction with environment and regulated reversibly by epigenetics at gene and protein level. Thus the skin antioxidant level will be decided eventually by the activity of enzyme and non-enzyme molecules on your skin . In a practical skincare, using a simple skin antioxidant test would help to know one’s skin antioxidant level, and determine which skincare products are best to suit you. In addition, it is also important to know whether your antioxidant skincare products are truly functional. Even if these products are claimed to contain antioxidant ingredients, the actual effect may be dependent on the ingredient amount, potency and the combination of multi-ingredients. Thus, before applying to skin, checking if these skincare product are truly functional against oxidative stress would be necessary for obtaining the skincare antioxidant products that are truly effective and suited for users.
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