Aging of the Gut Microbiome as a Contribution to Sarcopenia
Here find a review of what is known of relationships between the aging of the gut microbiome and aging of skeletal muscle. With age, everyone loses muscle mass and strength, leading eventually to sarcopenia and frailty. A perhaps surprisingly large fraction of this is a consequence of too little physical activity, as judged when comparing hunter-gatherer populations with the much more sedentary developed world. Other mechanisms of aging are important, however. The gut microbiome changes in composition with age, and this both increases chronic inflammation and reduces the supply of beneficial metabolites to tissues in the body. It remains to be seen as to how large this effect is versus others, but it is at least a contribution that can be addressed more readily than most.
Sarcopenia is a skeletal muscle disorder, with primary sarcopenia defined as an age-related progressive loss of skeletal muscle mass, strength, and physical function. This condition is notably prevalent, ranging from 10% to 27% in individuals aged 60 years and older. At present, it is known that primary sarcopenia is multifactorial and not limited to age-related lifestyle changes (e.g., physical inactivity and low-protein diet), inflammation, and insulin resistance. These factors contribute to alterations in muscle protein turnover as well as the development and progression of sarcopenia. However, the extent of other factors that may contribute to sarcopenia development is not fully understood, and the precise underlying mechanisms of sarcopenia remain elusive.
The gut microbiota, consisting of over 100 trillion bacterial cells, plays a vital role in human metabolic and immunological health. The gut microbiota can produce a wide range of bioactive compounds, mainly including short-chain fatty acids (SCFAs), secondary bile acids, branched-chain amino acids, and many others, to impact host physiology and health via different host-microbe metabolic pathways. Once in the bloodstream, SCFAs exhibit epigenetic and immunomodulatory effects on various organs, contributing to the development of a range of human diseases, including primary sarcopenia.
Gut dysbiosis, an imbalanced gut microbiota resulting from compositional changes, has been associated with aging as well as various age-related health conditions and diseases, including sarcopenia. Gut dysbiosis and sarcopenia commonly occur in older individuals. Convincing evidence from animal and human studies has linked gut dysbiosis to sarcopenia, with a recent study suggesting a causal relationship. While the factors influencing human gut microbiomes are complex throughout the lifespan, age itself has been shown to adversely affect the diversity of gut microbiomes and their beneficial metabolites. This impact may contribute to age-related diseases, including sarcopenia.
Studies have demonstrated that Bifidobacterium and Lactobacillus supplements enhance muscle mass and strength in aged mice, and similar benefits have been observed with a prebiotic formulation in elderly individuals. However, it remains unclear whether there is a direct impact of gut microbiota on muscle mass, function, and the development of sarcopenia. It is also challenging to pinpoint the specific gut microbiomes and their metabolites that are beneficial to muscle health and could serve as therapeutic targets. Additionally, it is still elusive how the gut microbiome and its metabolites regulate the gut-muscle axis, a topic of ongoing investigation. Further research is needed to fully understand the mechanisms and to explore potential therapeutic interventions targeting the gut microbiota to prevent or treat sarcopenia, thus promoting healthy aging.