Arguing for Aging of the Gut Microbiome to Worsen the Burden of Cellular Senescence

We should expect most of the various different aspects of aging to strongly interact with one another, leading to worse outcomes. Degenerative aging accelerates as it progresses precisely because of such harmful interactions. Researchers here discuss a still novel view of the way in which age-related changes in the gut microbiome may lead to greater harms resulting from the burden of senescent cells present in aged tissues. Incidentally, both the aging of the gut microbiome and the accumulation of senescent cells have bidirectional relationships with age-related immune system dysfunction. Near all aspects of aging interact.

Understanding the relationship between the gut microbiome and healthy aging is fundamental to achieving systemic longevity. Cellular senescence - a major hallmark of aging - is a promising area of research that requires investigation with relation to microbial dysbiosis. As an inevitable, age-related process, cellular senescence can cause severe damage to the host upon accumulation, largely due to overexpression of the senescence-associated secretory phenotype (SASP) and associated metabolic dysregulation.

Data from recent findings suggest an intricate relationship to exist between the gut microbiome, cellular senescence, and skin health. This proposed relationship is anchored by the SASP and largely influences the aging phenotype and associated diseases. The skin is vulnerable to the accumulation of senescent cells due to its external exposures (e.g., UV radiation). Recent literature suggests senescence to partake in numerous cutaneous diseases, all of which compromise function of the skin and general health. The link between skin homeostasis and healthy aging is further supported by recent evidence demonstrating systemic detrimental effects from chronic senescence in the skin, likely through paracrine signaling. Moreover, the presence of bacterial metabolites in the skin due to the gut-skin crosstalk can disrupt skin health, one way being further aggravation of the SASP.

Recent investigation has drawn correlations between gut composition and cellular senescence and revealed a distinct microbial composition in the gut in response to senolytic treatment. However, additional studies are needed to advance knowledge on microbial composition and function in the presence of accumulated senescence. Metabolomics is one approach that can help characterize metabolites found systemically and in the skin in order to quantify the impact of specific metabolic activity on senescence.


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