Yuki Saito1† and Takako S. Chikenji 1,2 * †1

Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan, 2 Department of Health Sciences, School of Medicine, Hokkaido University, Sapporo, Japan

Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of aging tissues or pathological contexts and may lead to progressive tissue degeneration. The mechanisms responsible for the effects of senescent cells have not been fully elucidated. Here, we review current knowledge about the beneficial and detrimental effects of senescent cells in tissue repair, regeneration, aging, and age-related disease, especially in skeletal muscle. We also discuss how senescence of muscle stem cells and muscle-resident fibro-adipogenic progenitors affects muscle pathologies or regeneration, and consider the possibility that immunosenescence leads to muscle pathogenesis. Finally, we explore senotherapy, the therapeutic targeting of senescence to treat agerelated disease, from the standpoint of improving muscle regeneration.

Keywords: senescence, skeletal muscle, chronic inflammation, aging, muscle regeneration, muscle stem cells, FAPs, fibrosis

Edited by:

Barbara St. Pierre Schneider, University of Nevada, Las Vegas, United States

Reviewed by: Keitaro Yamanouchi, The University of Tokyo, Japan Antoneta Granic, Newcastle University, United Kingdom

*Correspondence: Takako S. Chikenji 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。†

ORCID: Yuki Saito orcid.org/0000-0002-7949-1628 Takako S. Chikenji orcid.org/0000-0003-2832-3656

Specialty section: This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

Received: 11 July 2021

Accepted: 23 August 2021

Published: 06 September 2021

Citation: Saito Y and Chikenji TS (2021) Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics. Front. Pharmacol. 12:739510.

doi: 10.3389/fphar.2021.739510