Considering the Contribution of the Gut Microbiome to Age-Related Frailty

Frailty is a condition with a strong inflammatory component. It isn't just physical weakness, but also the vulnerability of an incapable and constantly overactive immune system, generating inflammatory signaling that disrupts tissue and organ function throughout the body. In recent years, there has been a considerable growth of interest in the gut microbiome and its contribution to aging. It is clear that microbial populations shift with age in ways that promote inflammatory engagement with the immune system. Replacing an old gut microbiome with a young gut microbiome, such as via fecal microbiota transplantation, produces a reduction in inflammation, improvement in function, and extension of life span in short-lived animal models. This is an approach to rejuvenation that could be fairly rapidly developed for human use, and certainly should receive more attention and funding than is presently the case.

Frailty is a clinical syndrome characterized by "diminished strength, endurance, and reduced physiological function". Frailty predisposes patients to negative health-related outcomes such as falls, hospitalization, disability, dependency, and mortality. The prevalence of frailty ranges from 4% to 59% in community-dwelling older adults and increases with age. Given the rapidly aging population, the United Nations estimates that worldwide, the number of people aged 60 years and above will double to nearly 2.1 billion by 2050. Therefore, frailty is a pressing concern in aging societies.

Microorganisms, as an environmental factor, are among the most interesting contributors to aging, and they provide a new perspective in understanding the aging process. As a person ages, progressive changes in intestinal tract physiology, the intestinal mucosal immune system, lifestyle changes (particularly in diet and exercise), medication, malnutrition, inflammation, and immune senescence may change the diversity, composition, and functional features of the gut microbiota. Data from animal models demonstrate that age-related microbial dysbiosis contributes to intestinal permeability, systemic inflammation, and premature mortality. Though the cause-and-effect relationship is unclear, age-related microbial dysbiosis is linked to unhealthy aging and geriatric syndromes, which include frailty. Identifying specific changes in frailty-related gut microbiota is essential in developing microbiome-based diagnostic and therapeutic strategies.

In this review, we first describe the relevant changes in gut microbiota related to aging and frailty. Subsequently, we summarize recent findings on the possible role of chronic low-grade inflammation in frailty and how microbial dysbiosis is involved in its pathogenesis, including frailty-related inflammation.


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