@article{d6d062a3131c43ff9635542b974d3cd7,
title = "Characterization of cellular senescence in aging skeletal muscle",
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 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.",
author = "Xu Zhang and Leena Habiballa and Zaira Aversa and Ng, {Yan Er} and Sakamoto, {Ayumi E.} and Englund, {Davis A.} and Pearsall, {Vesselina M.} and White, {Thomas A.} and Robinson, {Matthew M.} and Rivas, {Donato A.} and Surendra Dasari and Hruby, {Adam J.} and Lagnado, {Anthony B.} and Jachim, {Sarah K.} and Antoneta Granic and Sayer, {Avan A.} and Diana Jurk and Lanza, {Ian R.} and Sundeep Khosla and Fielding, {Roger A.} and Nair, {K. Sreekumaran} and Schafer, {Marissa J.} and Passos, {Jo{\~a}o F.} and LeBrasseur, {Nathan K.}",
note = "Funding Information: We are grateful for the support of the National Institutes of Health, National Institute on Aging for grants P01 AG062413, R01 AG055529 and R56 AG060907 to N.K.L. and R01 AG068048 and UG3CA 268103 to J.F.P. and T32 AG049672 to D.A.E. This work was also supported by the Glenn Foundation for Medical Research and the Pritzker Foundation (N.K.L.). X.Z. was supported by a Robert and Arlene Kogod Center on Aging Career Development Award. L.H. was supported by NIHR Newcastle Biomedical Research Centre grant awarded to the Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. R.A.F. and D.A.R. are partially supported by the US Department of Agriculture under agreement no. 58-8050-9-004 and by and by National Institutes of Health Boston Claude D Pepper Center (OAIC; 1P30AG031679). Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. We also thank members of P01 AG062413 (PI, S.K.) for helpful discussions, J.M. Cunningham and E. Wieben within the Mayo Clinic Genome Analysis Core for RNA-seq, Y. Li within the Division of Computational Biology and Department of Quantitative Health Sciences for assistance with bioinformatic analyses and staff at the Optical Microscopy Core within the Mayo Clinic Center for Cell Signaling in Gastroenterology (P30 DK084567) for guidance and use of imaging equipment. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = jul,
doi = "10.1038/s43587-022-00250-8",
language = "English (US)",
volume = "2",
pages = "601--615",
journal = "Nature Aging",
issn = "2662-8465",
publisher = "Springer",
number = "7",
}