Gut Dysbiosis and Muscle Aging: Searching for Novel Targets against Sarcopenia

Abstract

Advanced age is characterized by several changes, one of which is the impairment of the homeostasis of intestinal microbiota. These alterations critically influence host health and have been associated with morbidity and mortality in older adults. "Inflammaging," an age-related chronic inflammatory process, is a common trait of several conditions, including sarcopenia. Interestingly, imbalanced intestinal microbial community has been suggested to contribute to inflammaging. Changes in gut microbiota accompanying sarcopenia may be attenuated by supplementation with pre- and probiotics. Although muscle aging has been increasingly recognized as a biomarker of aging, the pathophysiology of sarcopenia is to date only partially appreciated. Due to its development in the context of the age-related inflammatory milieu, several studies favor the hypothesis of a tight connection between sarcopenia and inflammaging. However, conclusive evidence describing the signaling pathways involved has not yet been produced. Here, we review the current knowledge of the changes in intestinal microbiota that occur in advanced age with a special emphasis on findings supporting the idea of a modulation of muscle physiology through alterations in gut microbial composition and activity.

Figure 1

Healthy microbiota is a balanced community of symbiont, commensal, and pathobiont microorganisms. Each microbial class confers distinct characteristics to the host. Either imbalance in alpha-diversity or variations of relative abundance of single microbial taxa results in microbiota imbalance. As such, a sterile inflammation occurs and may predispose the host to opportunistic infections, ultimately leading to acute inflammation.

Figure 2

Proposed crosstalk between mitochondrial dysfunction and inflammation in muscle wasting. Imbalanced gut microbiota contributes to host inflammation and fuels the age-associated impairment of mitochondrial quality control in myocytes. This may lead to the release of mitochondrial damage-associated molecular patterns (DAMPs), such as mtDNA and ATP. The subsequent recruitment of local macrophages may maintain a persistent inflammatory milieu by alerting circulating immune cell and mounting a systemic response through the activation of mtDNA-induced inflammatory pathways. Cytokines, chemokines, nitric oxide (NO), and reactive oxygen species (ROS), released in the circulation by inflammatory cells, can induce further mitochondrial damage, thereby establishing a vicious circle and eventually contributing to muscle wasting. ETC: electron transport chain; mtDNA: mitochondrial DNA; TFAM: mitochondrial transcription factor A; PAMPs: pathogen-associated molecular patterns.