Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential

Yongyu He; Wenqing Xie; Hengzhen Li; Hongfu Jin; Yi Zhang; Yusheng Li

doi:10.3389/fcell.2021.793088

Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential

Front Cell Dev Biol. 2022 Jan 10:9:793088. doi: 10.3389/fcell.2021.793088. eCollection 2021.

Authors

Yongyu He^{1

2}, Wenqing Xie^{1

3}, Hengzhen Li^{1

3}, Hongfu Jin^{1

3}, Yi Zhang^{1

3}, Yusheng Li^{1

3}

Affiliations

¹ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.
² Xiangya School of Medicine, Central South University, Changsha, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Abstract

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/p21^CIP1 and p16^INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP) while 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.

Keywords: aging; cellular senescence; muscle stem cells (MuSCs) dysfunction; sarcopenia; senescence-associated secretory phenotype (SASP).

Publication types

Review