The Gut Microbiome as a Contributing Cause of Sarcopenia

Sarcopenia is the name given to more severe manifestations of the characteristic age-related loss of muscle mass and strength that occurs in all older people. A review of the literature will find ongoing debates over many possible contributing causes of this muscle degeneration, some with better evidence than others, many related to one another: lower dietary intake of protein in the elderly; a failure to correctly process dietary amino acids, particularly leucine; degeneration in the connections between muscle and nervous system; declining activity in muscle stem cell populations; chronic inflammation such as that produced by senescent cells; lack of exercise, particularly strength training; and so forth. From where I stand, I'd say the stem cell explanation is by far the most robust, but then one has to think about why the stem cell populations are in decline.

The open access paper here weighs in with thoughts on age-related changes in the types and behavior of bacteria in the gut as a contributing cause of sarcopenia. A great deal of attention has been given to the gut microbiome in the context of aging in recent years. It is most likely in the same order of magnitude of influence as diet when it comes to the relationship between metabolism and natural variations in the pace of aging, as it mediates diet. These bacteria also produce a wide range of compounds that affect cellular populations throughout the body in various ways, and appear particularly relevant in the chronic inflammation that arises in older individuals. But is it as important as other mechanisms in driving accumulation of the forms of cell and tissue damage outlined in the SENS rejuvenation research proposals, which in turn produce outcomes such as stem cell decline? Perhaps, perhaps not.

The progressive loss of skeletal muscle mass and strength/function, referred to as sarcopenia, is increasingly recognized as a relevant determinant of negative health outcomes in late life. However, the incomplete knowledge of the pathophysiology of sarcopenia hampers the identification of targets that could be exploited for drug development. A growing body of evidence suggests that the innumerable microorganisms that populate the mammalian gastrointestinal tract (gut microbiota) are tightly linked to the aging process of their host. Indeed, this microbial community, mostly composed of bacteria, participates in crucial activities of the gut barrier including the generation of metabolites essential for several host functions and the mediation of exogenous chemical effects on their host.

Age-related changes in the bacterial composition of the microbiota are well known, and alterations of gut microbiota driven by the diet may affect the health of elderly people. However, the complexity of mammalian gut microbiota and the technical challenges in isolating specific "prolongevity" microbial variants limit the knowledge of the microbiota to taxonomic and metagenomic profiling. The functions of individual microbial genes and the molecular mechanisms through which they intervene in host aging are yet to be elucidated. Even less is known about the implications of microbiota-immune system crosstalk on muscle aging.

Most gut microbial changes observed during aging are attributable to diet composition. Both environmental and behavioral factors, including loss of sensation, tooth loss, chewing difficulties, changes in lifestyle, increased consumption of high sugar-fat foods and reduction in plant-based foods have been suggested to influence age-associated diet variations. Taken as a whole, current data supports a link between aging and microbiota alterations relying on a proinflammatory loop. In this context, the age-related decline in masticatory function together with a reduction of appetite and gastrointestinal motility induces dietary changes (reduction in fruits and vegetables) that is reflected in microbiota rearrangement (dysbiosis). This alteration, in turn, can activate a proinflammatory loop fueled by the immunosenescence of gut-associated lymphoid tissue releasing proinflammatory mediators which further favors microbiota rearrangements.

Gut microbiota plays a crucial role in maintaining the balance of pro- and anti-inflammatory responses. Aged gut microbiota may elicit an inflammatory response and display lower capability of counteracting adverse microbes or removing their metabolites. The entrance of pathogens into the intestinal mucosa is also facilitated by the secretion of mucins by intestinal epithelial cells, which is triggered by a reduction in short-chain fatty acids (SCFA) levels in the intestines. SCFA serves within the gut not only as an energy source for colonic epithelial cells but also as strong anti-inflammatory molecules regulating host metabolism and immunity. Increased intestinal permeability to lipopolysaccharide (LPS) is another element in support of a mechanistic link between microbial dysbiosis and systemic inflammation.

In such a context, chronic inflammation may represent the unifying trait of microbial alterations and the development of muscle-wasting conditions in advanced age through a gut microbiota-muscle crosstalk. The molecular players involved in this process are not yet fully understood, but results from several studies indicate the relevant contribution of microbial changes and activity in the gut to the repertoire of inflammatory molecules involved in the milieu characterizing muscle aging. This represents an important matter to be addressed by future investigations to unravel the signaling pathways that may serve as targets for interventions.

Link: https://doi.org/10.1155/2018/7026198

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