Fight Aging!

Every age-related disease that can be linked to the chronic inflammation of aging is likely driven in part by the accumulation of senescent cells. This is not only a matter of senescent cells present in the organs affected by disease, but also involves the burden of cellular senescence throughout the body. When lingering in significant numbers, senescent cells cause harm via their inflammatory secretions, the senescence-associated secretory phenotype (SASP). Secreted inflammatory signals can travel widely through the body, rousing the immune system to overactivity, and changing cell behavior for the worse.

Sarcopenia is the characteristic loss of muscle mass and strength that takes place with age. Linking sarcopenia to chronic inflammation, and indeed to senescent cells, is a new idea in the sense that the modern focus on cellular senescence in aging only began in earnest a decade ago or so (after another prior decade of a few voices trying to get more researchers to take it seriously). With the development of senolytic therapies to selectively destroy senescent cells in full swing for a few years now, scientists have been writing papers on the plausible role of cellular senescence in sarcopenia. Today's open access materials are an example of the type.

Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential

Aging promotes most degenerative pathologies in mammals, which are characterized by progressive decline of function at molecular, cellular, tissue, and organismal levels and account for a host of health care expenditures in both developing and developed nations. Sarcopenia is a prominent age-related disorder in musculoskeletal system. Defined as gradual and generalized chronic skeletal muscle disorder, sarcopenia involves accelerated loss of muscle mass, strength, and function, which is associated with increased adverse functional outcomes and evolutionally refers to muscle wasting accompanied by other geriatric syndromes.

More efforts have been made to clarify mechanisms underlying sarcopenia and new findings suggest that it may be feasible to delay age-related sarcopenia by modulating fundamental mechanisms such as cellular senescence. Cellular senescence refers to the essentially irreversible growth arrest mainly regulated by p53/p21CIP1 and p16INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP). Cellular senescence may have beneficial functions in counteracting cancer progression, tissue regeneration, and wound healing.

By now diverse studies in mice and humans have established that targeting cellular senescence is a powerful strategy to alleviating sarcopenia. However, the mechanisms through which senescent cells contribute to sarcopenia progression need to be further researched. We review the possible mechanisms involved in muscle stem cells (MuSCs) dysfunction and the SASP resulting from cellular senescence, their associations with sarcopenia, current emerging therapeutic opportunities based on targeting cellular senescence relevant to sarcopenia, and potential paths to developing clinical interventions genetically or pharmacologically.