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The depletion of skeletal muscle satellite cells with age is concomitant with reduced capacity of single progenitors to produce reserve progeny
Open accessAbstract
Satellite cells are myogenic progenitors that reside on the myofiber surface and support skeletal muscle repair. We used mice in which satellite cells were detected by GFP expression driven by nestin gene regulatory elements to define age-related changes in both numbers of satellite cells that occupy hindlimb myofibers and their individual performance. We demonstrate a reduction in satellite cells per myofiber with age that is more prominent in females compared to males. Satellite cell loss also persists with age in myostatin-null mice regardless of increased muscle mass. Immunofluorescent analysis of isolated myofibers from nestin-GFP/Myf5(nLacZ/+) mice reveals a decline with age in the number of satellite cells that express detectable levels of betagal. Nestin-GFP expression typically diminishes in primary cultures of satellite cells as myogenic progeny proliferate and differentiate, but GFP subsequently reappears in the Pax7(+) reserve population. Clonal analysis of sorted GFP(+) satellite cells from hindlimb muscles shows heterogeneity in the extent of cell density and myotube formation among colonies. Reserve cells emerge primarily within high-density colonies, and the number of clones that produce reserve cells is reduced with age. Thus, satellite cell depletion with age could be attributed to a reduced capacity to generate a reserve population.
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“For example, in rodent studies, older (aged 19–25 months) compared with younger (aged 3–8 months) mice show impaired muscle regenerative capacity due to reduced satellite cell proliferation and differentiation,”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [30]
In the citing paper
“To retain their anatomical integrity and function, muscles need continuous repair and maintenance, and some evidence exists that the repair mechanism is dysfunctional in older individuals.”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [30]
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“and this deficit can be substantially reduced in parabiotic experiments when older animals are exposed, by cross-transfusion of blood, to the circulation of a genetically identical younger animal.29-31”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [30]
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“Constitutively active satellite cells also cause precocious differentiation (i.e., premature and excessive differentiation), further reducing the satellite cell pool and regenerative capacity of muscle [132,133].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [132]
In the citing paper
“This is noteworthy as there are particular muscle wasting conditions where satellite cells are constitutively active as inflammation is elevated, thus impairing their ability to self-renew [132,133].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [132]
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Metadata
- Authors
- Day, K., Shefer, G., Shearer, A., & Yablonka-Reuveni, Z.
- Affiliations
- University of Washington (US)
- Tel Aviv University (IL)
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 340
- Issue
- 2
- Pages
- 330-343
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC2854302
- OpenAlex
- W2065486527
- Cited by
- 254
- References
- 70
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 12 · 2023: 13 · 2022: 17 · 2021: 24 · 2020: 19 · 2019: 11 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 18 · 2014: 18 · 2013: 20 · 2012: 23
- FWCI
- 8.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RO1 AG021566)
- Genetic Approaches to Aging Training Program (T32 AG000057)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Keywords
- skeletal muscle satellite cells, aging, myogenic progenitor cells, Pax7, clonal analysis, myofiber regeneration, sex differences, myostatin, myotube formation, muscle repair
- MeSH terms
- Aging, Animals, beta-Galactosidase, Cell Separation, Cells, Cultured, Clone Cells, Female, Fluorescent Dyes, Heterozygote, Immunohistochemistry, Indoles, Intermediate Filament Proteins, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Tissue Proteins, Stem Cells, Cohort Studies, Mice, Knockout, Muscle, Skeletal, Transgenes, Fluorescent Antibody Technique, Indirect, Satellite Cells, Skeletal Muscle, Green Fluorescent Proteins, Mice, PAX7 Transcription Factor, Nestin
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