The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
Characterization of cellular senescence in aging skeletal muscle
Open accessAbstract
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.
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“Several studies have used single-cell technologies to successfully identify senescence-associated signatures in the context of aging12,13.”
From Spatial mapping of cellular senescence: emerging challenges and opportunities (2023) · cites this paper as [12]
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“γ-H2A.X is formed by post-translational modifications triggered by DSBs, while 53BP1 is recruited to DSBs in response to damage undergoing RNA-mediated condensation21.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [21]
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Spatial reconstruction of single-cell gene expression data
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F., & Regev, A. (2015) · Nature Biotechnology · doi:10.1038/nbt.3192 · Cited by 7,055
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670
Self-citationFielding, R. A., Vellas, B., Evans, W. J., Bhasin, S., Morley, J. E., Newman, A. B., Abellan van Kan, G., Andrieu, S., Bauer, J., Breuille, D., et al. (2011) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2011.01.003 · Cited by 3,256
Self-citationCellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225
Self-citationHallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605
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Items 201–206 of 206
Mazonson, B. R., Kim, Y.-T., & Thompson, L. V. (2026) · Translational Exercise Biomedicine · doi:10.1515/teb-2026-0016
Aging of Skeletal Muscle: From Molecular Mechanisms to Therapeutic Interventions
Liu, T., & Hu, Y. (2026) · MedComm · doi:10.1002/mco2.70995
“By disrupting mechanical integrity, metabolic homeostasis, vascular and neuromuscular support, and intercellular communication, these processes mark a shift from a regenerative tissue state toward a degenerative and poorly adaptive muscle niche [ 6, 23 ].”
Sun, S., Liu, J., Pan, X., Yang, Y., & Wei, Z. (2026) · Biomolecules · doi:10.3390/biom16091376
“Aging and repeated mechanical injury can push satellite cells into a senescent state characterized by cell-cycle arrest and SASP-mediated inflammation [96,97].”
Chen, Y., Gong, T., Shan, Z., Lai, J., 徐以明, Zhao, H., & Zhu, L. (2026) · The FASEB Journal · doi:10.1096/fj.202602956rr
Kim, C., Wi, J.-K., Koo, K., Cho, K.-M., Kim, C., & Kim, T. P. (2026) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2026.119296
Girón, M. D. S. C., Manzano, M., Pereira, S. L., Reinoso, A., Burgio, C., Montero-Martin, N., Jiménez-Jiménez, G., Argilés, J. M. A., Rueda, R., López-Pedrosa, J. M., et al. (2026) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.70412
“Interestingly, an enhancement of the p21 pathway has been described recently in animal and human models of muscle ageing [43, 44], supporting the idea that a decrease in AQP4 expression in ageing could be responsible for the molecular events described.”
Metadata
- Authors
- Zhang, X., Habiballa, L., Aversa, Z., Ng, Y. E., Sakamoto, A. E., Englund, D. A., Pearsall, V. M., White, T. A., Robinson, M. M., Rivas, D. A., Dasari, S., Hruby, A. J., Lagnado, A. B., Jachim, S. K., Granic, A., Sayer, A. A., Jurk, D., Lanza, I. R., Khosla, S., Fielding, R. A., Nair, K. S., Schafer, M. J., Passos, J. F., & LeBrasseur, N. K.
- Affiliations
- Mayo Clinic (US)
- Oregon State University (US)
- Tufts University (US)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- Corresponding author
- Passos, João F.
- LeBrasseur, Nathan K.
- ORCID
- Zhang, Xu
- Habiballa, Leena
- Ng, Yan Er
- Englund, Davis A.
- White, Thomas A.
- Robinson, Matthew M.
- Rivas, Donato A.
- Dasari, Surendra
- Hruby, Adam J.
- Lagnado, Anthony B.
- Jachim, Sarah K.
- Granic, Antoneta
- Sayer, Avan A.
- Jurk, Diana
- Lanza, Ian R.
- Khosla, Sundeep
- Fielding, Roger A.
- Nair, K. Sreekumaran
- Schafer, Marissa J.
- Passos, João F.
- LeBrasseur, Nathan K.
- Venue
- Nature Aging
- Published
- 2022-07-15
- Volume
- 2
- Issue
- 7
- Pages
- 601-615
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC9491365
- OpenAlex
- W4285490572
- Cited by
- 206
- References
- 64
- Citations by year
- 2026: 48 · 2025: 57 · 2024: 53 · 2023: 42 · 2022: 6
- FWCI
- 24.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Glenn Foundation for Medical Research
- Robert and Arlene Kogod Center on Aging Career Development Award
- NIHR Newcastle Biomedical Research Centre grant
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (T32 AG049672, P01 AG062413, 1P30AG031679, R00 AG058798, R01 AG068048, UG3CA 268103, R01 AG055529, R56 AG060907)
- U.S. Department of Agriculture
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, skeletal muscle aging, fibro-adipogenic progenitors, p16INK4a, p21, muscle fibers, DNA damage, chromatin reorganization, senotherapeutics, muscle strength, age-related decline, human skeletal muscle
- MeSH terms
- Aging, Animals, Humans, Phenotype, Cellular Senescence, Muscle, Skeletal, Cyclin-Dependent Kinase Inhibitor p16, Mice
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