Human muscle stem cells are refractory to aging
Open accessPublished version of a preprint
Abstract
Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third potential option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study, we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle microenvironment such as to disfavor the myogenic function of these cells.
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Muscle samples taken from cadavers maintained their myogenic potential after being transplanted into immunodeficient mice, with no declines in regenerative potential up to 78 years of age.
“a recent study in humans utilized xenotransplantation to determine whether muscle samples taken from cadavers maintained their myogenic potential after being transplanted into immunodeficient mice and found no declines in regenerative potential up to 78 years of age”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Novak et al., 2021
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- Authors
- Novak, J. S., Mázala, D. A. G., Nearing, M., Hindupur, R., Uapinyoying, P., Habib, N. F., Dickson, T., Ioffe, O. B., Harris, B. T., Fidelia‐Lambert, M. N., Rossi, C. T., Hill, D. A., Wagner, K. R., Hoffman, E. P., & Partridge, T. A.
- Affiliations
- Children's National (US)
- National Institutes of Health (US)
- University of Maryland, Baltimore (US)
- Georgetown University Medical Center (US)
- Department of Pathology Howard University Hospital Washington DC USA
- Kennedy Krieger Institute (US)
- Binghamton University (US)
- Corresponding author
- Novak, James S.
- Partridge, Terence A.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2021-06-05
- Volume
- 20
- Issue
- 7
- Pages
- e13411-e13411
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC8282247
- OpenAlex
- W3164552082
- Cited by
- 24
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 5
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Foundation to Eradicate Duchenne
- Muscular Dystrophy Association (MDA295203, MDA480160)
- Parent Project Muscular Dystrophy
- Duchenne Parent Project
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AG051260, T32AR056993)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- muscle stem cells, satellite cells, aging, sarcopenia, muscle regeneration, myogenic potential, xenotransplantation, muscle microenvironment, age-related muscle loss
- MeSH terms
- Aging, Animals, Disease Models, Animal, Humans, Xenograft Model Antitumor Assays, Satellite Cells, Skeletal Muscle, Mice
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