TitleCharacterization of cellular senescence in aging skeletal muscle
Publication TypeJournal Article
Year of Publication2022
AuthorsZhang, X, Habiballa, L, Aversa, Z, Ng, YEr, Sakamoto, AE, Englund, DA, Pearsall, VM, White, TA, Robinson, MM, Rivas, DA, Dasari, S, Hruby, AJ, Lagnado, AB, Jachim, SK, Granic, A, Sayer, AA, Jurk, D, Lanza, IR, Khosla, S, Fielding, RA, K. NAIR, SREEKUMARAN, Schafer, MJ, Passos, JF, LeBrasseur, NK
JournalNature Aging
Pagination601 - 615
Date Published07/2022

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 p16Ink4a 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 p21Cip1. 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.

Short TitleNat Aging