Geroconversion of aged muscle stem cells under regenerative pressure
Open accessAbstract
Regeneration of skeletal muscle relies on a population of quiescent stem cells (satellite cells) and is impaired in very old (geriatric) individuals undergoing sarcopenia. Stem cell function is essential for organismal homeostasis, providing a renewable source of cells to repair damaged tissues. In adult organisms, age-dependent loss-of-function of tissue-specific stem cells is causally related with a decline in regenerative potential. Although environmental manipulations have shown good promise in the reversal of these conditions, recently we demonstrated that muscle stem cell aging is, in fact, a progressive process that results in persistent and irreversible changes in stem cell intrinsic properties. Global gene expression analyses uncovered an induction of p16(INK4a) in satellite cells of physiologically aged geriatric and progeric mice that inhibits satellite cell-dependent muscle regeneration. Aged satellite cells lose the repression of the INK4a locus, which switches stem cell reversible quiescence into a pre-senescent state; upon regenerative or proliferative pressure, these cells undergo accelerated senescence (geroconversion), through Rb-mediated repression of E2F target genes. p16(INK4a) silencing rejuvenated satellite cells, restoring regeneration in geriatric and progeric muscles. Thus, p16(INK4a)/Rb-driven stem cell senescence is causally implicated in the intrinsic defective regeneration of sarcopenic muscle. Here we discuss on how cellular senescence may be a common mechanism of stem cell aging at the organism level and show that induction of p16(INK4a) in young muscle stem cells through deletion of the Polycomb complex protein Bmi1 recapitulates the geriatric phenotype.
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Satellite cells from geriatric mice show elevated p16Ink4a expression.
“Satellite cells derived from geriatric mice (28–32 months of age) exhibit elevated expression of p16Ink4a (53).”
From Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span (2021) · cites this paper as [53]
The opening passage and “Satellite Cell Geroconversion” report elevated p16Ink4a in satellite cells from geriatric mice, including high expression under proliferative pressure. Our copy does not specify that those mice were 28–32 months old, so the age range in the citing sentence is not verified. (LLM, conf=0.84)
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Cellular senescence in aging and age-related disease: from mechanisms to therapy
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Intrinsic and extrinsic mechanisms regulating satellite cell function
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Control of satellite cell function in muscle regeneration and its disruption in ageing
Sousa-Victor, P., García-Prat, L., & Muñoz-Cánoves, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00421-2 · Cited by 476 · see citing works
Self-citationSenolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span
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“Satellite cells derived from geriatric mice (28–32 months of age) exhibit elevated expression of p16Ink4a (53).”
BackgroundThe ins and outs of muscle stem cell aging
Brack, A. S., & Muñoz-Cánoves, P. (2015) · Skeletal Muscle · doi:10.1186/s13395-016-0072-z · Cited by 166 · see citing works
Self-citationMuscle stem cell aging: regulation and rejuvenation
Sousa-Victor, P., García-Prat, L., Serrano, A. L., Perdiguero, E., & Muñoz-Cánoves, P. (2015) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.03.006 · Cited by 163 · see citing works
Self-citation
- Authors
- Sousa-Victor, P., Perdiguero, E., & Muñoz-Cánoves, P.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Perdiguero, Eusebio
- ORCID
- Perdiguero, Eusebio
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2014-10-15
- Volume
- 13
- Issue
- 20
- Pages
- 3183-3190
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC4615107
- OpenAlex
- W2045410669
- Cited by
- 68
- References
- 97
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 1 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 1
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- E-Rare
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- satellite cells, cellular senescence, p16INK4a, Rb/E2F pathway, muscle regeneration, sarcopenia, stem cell aging, BMI1, Polycomb complexes, stem cell quiescence, gene expression profiling
- MeSH terms
- Animals, Humans, Regeneration, Stem Cells, Cellular Senescence, Satellite Cells, Skeletal Muscle
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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