Skin microbiome through the aging process

Aging is a major challenge of this century, with increasing efforts focusing on understanding the underlying physiological mechanisms and even investigating ways to maximize and control longevity.

Aging of the skin, a complex organ, is a visible part of the aging process. As we see the appearance of the visible signs of skin aging, such as wrinkles and ‘spots’ caused by pigment irregularities, it is also important to consider the role of the skin microbiota (also referred to as the microbiote) − the collection of microorganisms living on our skin surface, including bacteria, fungi and viruses (1).

A healthy skin microbiome, the ‘biotope’ between microbiota and human tissue, is determined by a combination of three environments on the skin that support the microbiota – sebaceous (waxy), moist and dry environments (2,3) – each of which supports a different array of microbes. However, in addition to these environments, age (along with gender and other host factors) has now also been shown to affect the skin microbiome balance (2,3).

Here we will take a look at the changes seen in our skin microbiome as we age and how such changes can affect our skin health and condition, as well as the ways in which this information can be used in efforts to slow or counteract the skin aging process…

Skin aging

Skin aging is physiologically characterized by a decrease in sweat and sebum (an oily, waxy substance produced by our skin’s sebaceous glands), resulting in alterations in skin surface physiology – for example, changes in pH and lipid composition (4,5). Linked to this, and due to additional structural alterations, we see skin aging manifest on the surface through the appearance of wrinkles, reduced firmness, flakiness and spots caused by pigment irregularities.

The immune system, a key component for maintaining the health and condition of our skin, also suffers the effects of aging, with individuals experiencing ‘immuno-senescence’ and reduced immune function as they grow older.

All these physiological changes can lead to an altered skin ecology and subsequently impact the skin microbiome (6). As well as the direct impact on the skin microbiome, this can also feed into our skin condition and overall health as the human microbiome equilibrium plays a key role in maintaining and protecting skin physiology and our immunity – all to be explored further on.

The aging skin microbiome

Research investigating the skin microbiome of individuals ranging from young to old age has shown a change in skin microbiome composition from infancy to adolescence (7), as well as differences according to the living environment when it comes to adult skin microbiome (8,9).

For example, when comparing the skin bacteria of Japanese women across two different age groups – younger (<35 years) and older (>60 years) – samples taken from four skin sites (one dry (forearm) and three sebaceous (scalp, forehead, cheek)) revealed that skin microbiome composition and diversity were strongly affected by both age and sample location. A higher diversity was observed in older skin relative to younger skin, and the samples from the forearm were particularly diverse. The scalp was characterized by lower diversity, which is thought to be due to the oily nature of this area versus the forearm and other sites (10).

The high diversity of the aged skin microbiome was largely due to the reduction of Cutibacterium acnes (previously known as Propionibacterium acnes, perhaps best known for its role in the acne), one of the most dominant bacterial groups on the skin, presenting an opportunity for other bacterial types to thrive. The decrease in C. acnes is thought to be related to reduced sebum secretion in older skin (11) – this reduction in sebum is typically observed in women due to hormonal changes during and after menopause (5), a significant age-related event for the female population. Moreover, C. acnes was also shown to preferentially populate areas of the skin that are rich in sebum-derived lipids, such as oleic acid, palmitic acid and mono-glycerides (12), with the density of C. acnes increasing in line with the total amount of lipids (13).

Although certain subtypes of C. acnes are indeed key microbes in acne development (referred to as ‘pathogenic phenotypes’), this bacteria is an important resident microorganism of the skin, with other types or ‘strains’ bringing crucial benefits. For example, through the secretion of antimicrobial substances and short-chain fatty acids, which contribute to anti-inflammatory effects and can initiate or strengthen immune responses (14). A reduction in C. acnes may reduce these skin benefits and thus contribute to the physiological signs of aging skin. The prevalence of C. acnes observed in younger groups may therefore suggest a gatekeeper or protective function for this type of bacteria that weakens as we age.

So, the research above shows that younger skin supports a less diverse microbiome, also with less variation across individuals observed relative to older subjects. Although the reasons are likely to be multi-factorial, these differences could be due to the fact that less nutrients are typically available on older skin due to age-associated reductions in skin cell renewal, sweat and sebaceous functions and a weakened immune function, leading to the demise of the dominant bacteria and increases in other ‘opportunistic’ species. The research also suggests that the age-related alteration of the skin microbiome could be skin site dependent, demonstrating that differences in the specific skin environment also play a part in mediating the effects.

One interesting point to note is that with increasing data on skin microbiome composition and diversity across different age groups, the skin microbiome could be used as a new indicator to quantify skin age irrespective of chronological age, providing a potential biomarker for determining and monitoring skin health.

Impact on skin health and condition

Many skin conditions (both clinical and subclinical) are associated with an imbalance in the skin microbiome.

When disrupted, imbalances within the skin microbiome can contribute to a wide variety of conditions such as acne, eczema, rosacea, dandruff, seborrheic dermatitis, atopic dermatitis and psoriasis. As an example, alterations in skin cell physiology associated with the disruption of the skin microbiota have been linked to major healing defects.

When such disorders are linked to age-related changes in skin structure and function, there are several contributing physiological factors thought to be responsible, including altered tissue metabolism, immune activity and hormonal control and balance, and environmental factors such as exposure to pollution and sun (leading to photo-aging).

Skin microbiome manipulation to manage the effects of aging

In recent years, the skin microbiome has become a hot topic for dietary supplements, cosmetics and therapeutic purposes.

Among dietary supplements and cosmetics, as microbiome-related research has trickled into the mainstream, there has been an increasing number of products that claim to protect and maintain the integrity and balance of the skin microbiota. Anti-aging is one area where the use of use of biotics (including prebiotics, probiotics and postbiotics) have shown potential…

Based on recent findings and further studies, for example, new skin biotics can be developed to reduce the incidence of age-related skin diseases (17,18) and skin disorders such as acne, as proposed by companies such as Lactobio in Denmark.

When it comes to the clinic, the possibility of manipulating the human skin microbiome to address skin conditions has opened exciting new paths – for example, skin bacteriotherapy and even skin microbiome transplantation. In line with this, biotechnology companies such as the startup S-Biomedic are already pioneering the development of skin microbiome manipulation techniques. S-Biomedic’s technology allows the transplantation of beneficial live bacteria (such as C. acnes) onto the skin of patients with certain conditions, and they are also developing topical formulations (19).

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References

1. Kong, H. H. Skin microbiome: genomics-based insights into the diverstiy and role of skin microbes. Trends Mol. Med. 17, 320–328 (2011)

2. Grice, E. & Segre, J. The skin microbiome. Nat. Rev. Microbiol. 9, 244–253 (2011).

3. Perez Perez, G. I. et al, Body site is a more determinant factor than human population diversity in the healthy skin microbiome. PLoS ONE 11, e0151990 (2016).

4. Farage, M. A. et al. Functional and physiological characteristics of the aging skin. Aging Clin. Exp. Res. 20, 195–200 (2008).

5. Pochi, P. E., Strauss, J. S. & Downing, D. T. Age-related changes in sebaceous gland activity. J. Invest. Dermatol. 73, 108–111 (1979).
6. Somerville, D. A. The normal flora of the skin in different age groups. Br. J. Dermatol. 81, 248–258 (1969).
7. Capone, K. A. et al. Diversity of the human skin microbiome early in life. J. Invest. Dermatol. 131, 2026–2032 (2011).

8. Leung, M. H. Y., Wilkins, D. & Lee, P. K. H. Insights into the pan-microbiome: skin microbial communities of Chinese individuals differ from other racial groups. Sci. Rep. 5, 11845 (2015).
9. Ying, S. et al. The influence of age and gender on skin-associated microbial communities in urban and rural human populations. PLoS ONE 10, e0141842 (2015).

10. Shibagaki, N. et al.  Aging-related changes in the diversity of women’s skin microbiomes associated with oral bacteria. Sci. Rep. 7, 10567 (2017).

11. Leyden, J. J. et al. Age-related changes in the resident bacterial flora of the human face. J. Invest. Dermatol. 65, 379–381 (1975).

12. Bouslimani, A. et al. Molecular cartography of the human skin surface in 3D. Proc. Natl. Acad. Sci. USA 112, 2120–2129 (2015)
13. McGinley, K. J. et al. Regional variations in density of cutaneous Propionibacteria: correlation of Propionibacterium acnes populations with sebaceous secretion. J. Clin. Microbiol. 12, 672–675 (1980).

14. Christensen, G. J. M. & Bruggemann, H. Bacterial skin commensals and their role as host guardians. Benef. Microbes 5, 201–215 (2014).
15. Zaura, E. et al. Defining the healthy ‘core microbiome’ of oral microbial communities. BMC Microbiol. 9, 259 (2009).
16. Fierer, N. et al. The influence of sex, handedness, and washing on the diversity of hand surface bacteria. Proc. Natl. Acad. Sci. USA 105, 17994–17999 (2008).

17. Zichao. L. et al. New Insights into the skin microbial communities and skin aging front. Microbiol. 13, 1021–1040 (2020).

18. Khmaladze, I. et al. The skin interactome: a holistic “genome-microbiome-exposome” approach to understand and modulate skin health and aging. Clin. Cosmet. Investig. Dermatol. 13, 1021-1040 (2020).

19. Paetzold, B. Skin microbiome modulation induced by probiotic solutions, Microbiome 7, 95 (2019).

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