How does oxidative stress impact the aging of human skin?
Human skin essentially consists of two basic layers: the epidermis on the surface and the dermis underneath, both joined together by the basal lamina. The aging process has different consequences depending on whether we are talking about the dermis or the epidermis. In the dermis, changes in the extracellular matrix play a key role in the processes of internal and external aging, which is most evident through the loss of collagen, elastic fibers and hyaluronic acid, which contributes to the formation of acidic acids.
In the context of intrinsic and extrinsic aging, an imbalance in the extracellular matrix plays an important role. Enzymes in the extracellular matrix, such as various metalloproteases and elastases, play a key role in the degradation of collagen, elastic fibers, and other structural components of the matrix. These changes in the matrix contribute to the formation of disorganized structures and the loss of functionality of the dermal meshwork, which is seen through the process of extrinsic aging such as photoaging.
Photoaging leads to a significantly accelerated degradation process, known as “ECM turnover”, resulting from increased production of reactive acids, activation of various signaling pathways, and expression of proteins such as transcriptional activator (trans1 AP factor). These changes contribute to the loss of functionality and structure of the skin but also open the way to various dermatological problems such as actinic keratoses and skin cancers.
In addition to aging, the extracellular matrix plays an important role in other dermatological problems such as vitiligo and other forms of hypopigmentation, where an imbalance in the matrix can contribute to an imbalance in melanin production and transport related to aging-related skin problems.
What are the key findings regarding the interaction between the microbiota and the skin barrier in aging skin?
The skin barrier can be represented as four interwoven factors consisting of microbial, immunological, chemical and physical barriers that are tightly coordinated with the commensal microbiota. The underlying mechanism by which the microbiota regulates skin barrier formation and repair has far-reaching implications for skin aging characterized by epidermal barrier dysfunction.
Skin microbes primarily act as a protective barrier against foreign and pathogenic microbes. Within polymicrobial communities, skin microbes have evolved mechanisms to compete with and directly antagonize potential rivals. Coagulase-negative Staphylococcus species (CoNS), such as Staphylococcus hominis and Staphilococcus capitis, antagonize the major skin pathogen Staphylococcus aureus, either through the production of unique antibiotics or interference with a specific quorum-sensing pathway. aureus virulence. In addition, some of these antagonistic mechanisms synergize with host antimicrobial responses, maximizing defense. Certain strains of Cutibacterium acnes secrete a thiopreptide antibiotic called cutamycin, which effectively limits the colonization of S. aureus. The role of these skin commensals as a microbial barrier is important because S. aureus has the powerful resources to damage the skin barrier and contribute to a pro-inflammatory state that can theoretically exacerbate skin inflammation/aging.
Commensal microbes also interact and modulate other functional levels of the skin barrier. First, skin microbes play a fundamental role in the induction, maintenance and homeostasis of the skin immune barrier. Under optimal conditions, the skin’s immune system seamlessly integrates the innate and adaptive branches of immunity, engaging in a dialogue that guides the selection, fine-tuning, and termination of responses as needed. A key aspect of this process is tissue repair, whereby acute skin damage triggers the release of ligands that activate keratinocytes and lead to the emission of inflammatory mediators. In such conditions, the specific component of S. epidermidis, known as lipoteichoic acid, helps reduce inflammation and aid wound healing by interacting with the innate immune receptor, Toll-like receptor 2 (TLR2). In the gastrointestinal system, certain microbes and microbial metabolic products influence the regulatory immune network. Similarly, Vitreoscilla filiformis, a Gram-negative bacterium found in spa waters, is known to promote the development of regulatory T cells in tissues and suppress T cell proliferation during skin inflammation in mice. Microbes that have regulatory and protective properties would be of great benefit in maintaining immune barrier homeostasis and controlling skin aging/inflammation.
In addition, C. acnes and Corinebacterium spp., produce lipases that break down triglycerides in sebum and release free fatty acids. Free fatty acids maintain an acidic surface of the skin, which dictates a chemical barrier.
Finally, Ubero et al., showed that skin commensals (a collection consisting of members of the Firmicutes phylum, i.e. Staphilococcus epidermidis, S. varneri, S. hemolyticus and members of the Actinobacteria phylum, i.e. Micrococcus luteus) and Corinebacterium play a key role . in restoring the physical barrier by stimulating the aryl hydrocarbon receptor (AhR) in keratinocytes. C. acnes also causes a significant increase in barrier lipids and proteins (ie, filaggrin and loricrin) in the epidermis, further contributing to the improvement of the physical barrier. S. epidermidis, another commensal skin bacterium, helps maintain the physical barrier by producing sphingomyelinase, which plays a role in ceramide production.
In the elderly, long-term antibiotic use can also lead to microbial dysbiosis, reducing microbial diversity. The method of application of antibiotics affects the microbiota of the skin differently. Topical antibiotics cause immediate, localized changes, while oral antibiotics affect the entire microbiome, including the fissure and skin axis, spreading the effect on skin health. In the elderly, antibiotic use is associated with increased dryness, likely due to changes in the microbiome affecting skin homeostasis and immune responses.
Which intrinsic and extrinsic factors contribute to skin aging?
Intrinsic skin aging factors
Ethnicity has the greatest effect on aging through different levels of pigmentation. A high level of pigmentation provides protection against the cumulative effects of photoaging, African-American skin shows little difference between sun-exposed and non-sun-exposed areas. When considering skin cancer susceptibility, pigmentation provides significant protection against UV radiation, and cancer rates that show significantly different levels of protection between whites and African Americans. Basal cell carcinoma and squamous cell carcinoma often occur in skin that is exposed to the sun, African American skin is tighter and has more content among the elderly. Research has also shown that fights in Asians appear later and with less significance compared to Caucasians, although the reason for this finding is not yet fully expressed.
Extrinsic skin aging factors
Cigarette smoking is strongly associated with elastosis in both sexes, which is reflected in loose skin, and telangiectasia (red spots on the skin) in men. The damage caused by smoking is primarily the result of reduced capillary blood flow to the skin, which leads to a lack of oxygen and nutrients in the skin tissues. Smoking also causes a decrease in collagen and elastin fibers in the dermis, which makes the skin loose, tight and less elastic. Cigarette smoke damages collagen and elastin not only in the extra tissue, but also in the skin. Additionally, nicotine constricts the vasculature and can contribute to wrinkles. Research has confirmed the link between smoking and the appearance of wrinkles on the skin, showing that smoking is associated with a higher risk of premature skin aging, even when other factors such as age control are controlled.
In what ways do natural polyphenols protect the skin from damage caused by solar radiation?

There is considerable interest in the use of natural plant products, including polyphenols, in the prevention of UV-induced photodamage and skin cancer risk. Dietary prepared polyphenols have anti-inflammatory, immunomodulatory and antioxidant properties, which makes them a promising group of compounds for chemopreventive strategies against various skin disorders, including cancer. Advances in our understanding of carcinogenesis at the cellular and molecular level have enabled the development of effective cancer prevention strategies, known as chemoprevention. This strategy is based on the use of specific natural or synthetic chemical substances that can prevent, slow down or reverse the processes of carcinogenesis. Chemoprevention offers a realistic possibility of controlling the risk of cancer, which is significant because the full effects of carcinogenic environmental factors are difficult to control, while individuals can modify their habits in non-use protection and lifestyle combined with damaging effects on the skin. Our researchers have demonstrated the effectiveness of natural polyphenols such as green tea polyphenols, milk thistle silymarin, and grape seed proanthocyanidins against UV-induced inflammation, oxidative stress, DNA damage, and damage.
References:
- Rinnerthaler, M., Bischof, J., Streubel, M. K., Trost, A., & Richter, K. (2015). Oxidative stress in aging human skin. Biomolecules, 5(2), 545-589. https://doi.org/10.3390/biom5020545
- Woo, Y. R., & Kim, H. S. (2024). Interaction between the microbiota and the skin barrier in aging skin: a comprehensive review. Frontiers in Physiology, 15, 1322205.
- Farage, M. A., Miller, K. W., Elsner, P., & Maibach, H. I. (2008). Intrinsic and extrinsic factors in skin aging: a review. International journal of cosmetic science, 30(2), 87-95.
- Nichols, J. A., & Katiyar, S. K. (2010). Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Archives of Dermatological Research, 302(2), 71-83. https://doi.org/10.1007/s00403-009-1001-3