Cellular senescence in skeletal muscle: age, sarcopenia, therapy

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Abstract

Progressive age-related decline in skeletal muscle mass, strength, and function results in muscle fiber loss and atrophy, with associated replacement by adipose and fibrous tissue, or sarcopenia. Muscles are subject to multiple forms of molecular and cellular damage, including impaired regenerative capacity, protein turnover, mitochondrial dysfunction, and cellular senescence, which manifests as cell cycle arrest. With age, these cells accumulate and acquire distinctive properties characterized by chromatin changes and the emergence of a specific secretory senescence-associated phenotype (SAS phenotype), which exerts local and/or systemic negative effects on organism tissues. The aim of this review is to present the cellular senescence landscape in the skeletal muscle based on the evidence for their role in age-related changes in muscle mass, strength, function, and clinical consequences of this phenomenon, denoting key directions for the development of new senescence-based therapies for sarcopenia. Methods: Inclusion criteria: randomized or non-randomized controlled trials investigating the role of cellular senescence in age-related changes and pathophysiology of skeletal muscles. Data were searched in the electronic scientific databases Google Scholar, Medline, PubMed, Scopus, Web of Science and Cochrane Library by keywords and their combinations using the AMSTAR 2 program. The selection of publications (82 included out of 430) was randomly performed, after which their methodological quality was independently assessed by the authors. The crucial role of cellular senescence with the formation of the secretory phenotype associated with aging (SAS phenotype) in the age-related pathophysiology of skeletal muscles has been proven. These phenomena alter muscle tissue homeostasis and contribute to the occurrence and progression of sarcopenia. The impact on senescent cells and their secretory profiles can contribute to the development of complex strategies, including the use of senolytics and senomorphs to improve the quality of life of older adults. On the other hand, currently, there is a lack of data on the vulnerability to aging of terminally differentiated skeletal muscle fibers and resident mononuclear cells of the interstitial microenvironment. There are different opinions on the contribution of this event to the onset and progression of age-related skeletal muscle mass loss and dysfunction, as well as the initiation of sarcopenia. Scientific advances in the study of cellular senescence will allow us to identify new therapeutic approaches to optimize muscle health in old age.

About the authors

N. G. Plekhova

Pacific State Medical University

Email: pl_nat@hotmail.com
Vladivostok, Russia

P. A. Novikova

Pacific State Medical University

Vladivostok, Russia

A. N. Voronova

Pacific State Medical University

Vladivostok, Russia

D. V. Korolev

Pacific State Medical University

Vladivostok, Russia

V. B. Shumatov

Pacific State Medical University

Vladivostok, Russia

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