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Characterization of cellular senescence in aging skeletal muscle

Authors :
Xu Zhang
Leena Habiballa
Zaira Aversa
Yan Er Ng
Ayumi E. Sakamoto
Davis A. Englund
Vesselina M. Pearsall
Thomas A. White
Matthew M. Robinson
Donato A. Rivas
Surendra Dasari
Adam J. Hruby
Anthony B. Lagnado
Sarah K. Jachim
Antoneta Granic
Avan A. Sayer
Diana Jurk
Ian R. Lanza
Sundeep Khosla
Roger A. Fielding
K. Sreekumaran Nair
Marissa J. Schafer
João F. Passos
Nathan K. LeBrasseur
Source :
Nat Aging
Publication Year :
2022

Abstract

Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16(Ink4a) together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2(Cip1). Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.

Details

ISSN :
26628465
Volume :
2
Issue :
7
Database :
OpenAIRE
Journal :
Nature aging
Accession number :
edsair.doi.dedup.....244e1fc49b2072e123743940eaa7f50b