Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1

Author(s):Show less -

Brett, Jamie O. ^{[1, 2, 3]} ; Arjona, Marina ^{[1, 2]} ; Ikeda, Mika ^{[1, 2]} ; Quarta, Marco ^{[1, 2, 4]} ; de Morree, Antoine ^{[1, 2]} ; Egner, Ingrid M. ^{[5, 1]} ; Perandini, Luiz A. ^{[6, 1]} ; Ishak, Heather D. ^{[1, 2]} ; Goshayeshi, Armon ^{[1, 2]} ; Benjamin, Daniel I. ^{[1, 2]} ; Both, Pieter ^{[1, 2, 3]} ; Rodriguez-Mateo, Cristina ^{[1, 2]} ; Betley, Michael J. ^{[1, 7]} ; Wyss-Coray, Tony ^{[1, 2, 4]} ; Rando, Thomas A. ^{[1, 2, 4, 8]}

Affiliation

^[1] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 - USA

^[2] Stanford Univ, Sch Med, Paul F Glenn Labs Biol Aging, Stanford, CA 94305 - USA

^[3] Stanford Univ, Sch Med, Stem Cell Biol & Regenerat Med Grad Program, Stanford, CA 94305 - USA

^[4] Vet Affairs Palo Alto Healthcare Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA 94304 - USA

^[5] Univ Oslo, Dept Biosci, Oslo - Norway

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[7] Stanford Univ, Sch Med, Neurosci Interdept Grad Program, Stanford, CA - USA

^[8] Vet Affairs Palo Alto Hlth Care Syst, Neurol Serv, Palo Alto, CA 94304 - USA

• Document type: Journal article
• Source: NATURE METABOLISM; v. 2, n. 4, p. 307+, APR 2020.
• Web of Science Citations: 1

Abstract

Ageing impairs tissue repair. This defect is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young-adult animals, but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem-cell function in the context of tissue regeneration are incompletely understood. Here, we show that exercise in the form of voluntary wheel running accelerates muscle repair in old mice and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGF-beta signalling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem-cell quiescence. (AU)

• FAPESP's process: 15/26767-1 - The role of non-canonical Stat3/TGF-B1 pathway in the satellite cells fate in mdx mice
• Grantee: Luiz Augusto Buoro Perandini
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor