Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence

Abstract

The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies.

Keywords: cellular senescence; disease; dysbiosis; gut microbiome; microbial metabolites; nutrition; prebiotics; probiotics; skin.

Figure 1

Gut microbiome and its impact on gut dysbiosis, aging and skin health. The consequences of senescent cell accumulation including gut microbial imbalance, subsequent increased gut barrier permeability, secretion of microbial metabolites and a resulting impairment to the skin. The senescence associated secretory phenotype (SASP) remains central to each of the factors presented. The pathogenesis of age-related and chronic diseases, systemic inflammation and immune decline results from the proposed interrelationship. UV = ultraviolet; UVR = ultraviolet radiation; F/B = Firmicutes/Bacteroidetes. Created with Biorender.com.

Figure 2

Schematic representation of the effects of cellular senescence on skin tissue. (A) A senescent cell secretes senescence associated secretory phenotype (SASP) factors for transient tissue benefits. (B) However, an accumulation of senescent cells results in significant harm to the host. An oversecretion of the proinflammatory SASP factors can onset systemic or chronic inflammation, cause frailty and induce senescence to normal neighboring cells via paracrine mechanisms. (C) SASP overexpression can also influence the development and pathology of several cutaneous diseases. IL = interleukin; TNF-α = tumor necrosis factor alpha; IFN-γ = interferon gamma; CXCLs = chemokine ligands; MMPs = matrix metalloproteinases; ROS = reactive oxygen species. Created with BioRender.com.