How Antioxidants Protect the Skin: Oxidative Stress, ROS, and Ageing Explained

Oxidation is a process in which a molecule gains or loses an electron. This can cause molecules to have at least one unpaired valence electron, which makes the molecule extremely reactive and unstable. A major type of free radical that are crucial in biological pathways are reactive oxygen species (ROS), which also play an important role in reactive oxygen species (ROS) in skincare. ROS are primarily beneficial in cells, are a natural biproduct of metabolism, and are necessary for proliferation and differentiation (Santos et al., 2018). These free radicals are destroyed by the body’s antioxidant system—often referred to as the antioxidant defence in skin. Antioxidants are compounds that inhibit oxidation in order to prevent free radical formation (Santos et al., 2018). The body’s antioxidant system is generally effective at clearance of free radicals; however, if the system is disrupted, reactive oxygen species can disrupt many cellular pathways, causing pathology. This overproduction and lack of destruction of ROS can block enzymatic cascades, disrupt cell membrane permeability, destroy DNA and prevent cellular energy generation (Sharifi-Rad et al., 2020). Therefore, it is vital that the body’s antioxidant system works effectively to maintain oxidative stress protection skincare benefits.

Oxidative stress, which occurs when ROS are being produced faster than they are neutralised, can negatively impact skin health and is central to oxidative stress and skin ageing. ROS are pathologically generated due to UV exposure, typically UVB, which causes direct damage to the skin due to its oxidative abilities (Sharifi-Rad et al., 2020). This connection highlights the importance of understanding UV damage and antioxidants, especially in the context of skin protection. UVB can oxidate a range of compounds, usually resulting in DNA damage in some way. This is cause for concern in skin cells, since DNA damage or activation of transcription pathways can alter the expression of genes responsible for Extracellular matrix (ECM) production. This changes how these cells interact with the environment, can indirectly activate inflammatory cascades, and can cause ECM degradation, causing skin-ageing effects such as wrinkle formation (Kammeyer and Luiten, 2015). Furthermore, if ROS cascades cause alterations to genes involved in tumour suppression, such as p53, p53 can become activated which will cause apoptosis of healthy keratinocytes (Kammeyer and Luiten, 2015). Alterations to the p53 gene can also cause dysfunction, resulting in loss of ability to induce apoptosis in cells that may begin to express tumour-morphology, increasing risk of tumour formation (Kammeyer and Luiten, 2015). It is important to understand how ROS cause pathological effects in order to understand antioxidant function.

Figure 1:

Figure 1: Diagram showing how UVA/UVB can cause ROS formation, and how ROS affect cellular function (Kammeyer and Luiten, 2015). UV-induced mutation and DNA damage can cause alteration of gene expression, having negative effects on skin cell function. ROS can upregulate MMP expression, inducing collagen degradation. Collagen degradation can also be induced via the G-protein signalling pathway, initiated by UVB-induced excitement of serine protease

Antioxidants appear naturally in the body and in the environment and reduce oxidative stress. Upregulating antioxidant pathways to the appropriate level can increase their efficiency, therefore reducing oxidative stress that causes DNA damage. There are 2 types of antioxidants: enzymatic and non-enzymatic antioxidants (Nakai and Tsuruta, 2021). Enzymatic antioxidants aim to return the oxidised species to its reduced form (Nakai and Tsuruta, 2021). Superoxide dismutase (SOD), often included in superoxide dismutase skincare formulations, neutralises superoxide (O2-) radicals. Catalase and glutathione peroxidase (GPx), both important in catalase and glutathione peroxidase skin health, neutralise Hydrogen peroxide (H2O2). Catalase malfunctions are associated with age-related degenerative diseases such as Alzheimer’s disease, cancer, vitiligo, hypertension, and diabetes mellitus. Some GPx neutralise lipid peroxidases too. Non-enzymatic antioxidants serve as electron donors to scavenged ROS (Nakai and Tsuruta, 2021). Vitamin E prevents lipid radical formation in cell membranes. Vitamin C reacts with superoxide and hydroxy (OH-) free radicals in the cytoplasm. Vitamin C and E in skin health are widely recognised due to their central role in maintaining antioxidant balance. Vitamin C and E form radicals once they have performed their neutralising actions, therefore these radicals need to be restored back to their neutral vitamin C and E state. Vitamin E radicals can be restored back to vitamin E through enzymatic reactions, whereas vitamin C must be oxidised in order for it to return to its restored vitamin C state. This occurs by Glutathione (GSH) action, in which Vitamin C is reduced and GSH is oxidised. To reverse the oxidation of GSH, NADPH is oxidised to NADP+.

Upregulating these antioxidant systems through increasing intake of non-enzymatic antioxidants, and targeting enzymatic ones through natural antioxidant ingredients for skin, reduces potential of oxidative stress in skin cells, which will decelerate the skin ageing process.