Cited by 68Muscle Physiology and DisordersTelomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model Organisms

Geroconversion of aged muscle stem cells under regenerative pressure

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Sousa-Victor, Pedro, Perdiguero, Eusebio, Muñoz-Cánoves, Pura·2014·Cell Cycle

Abstract

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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Crossref · 10.4161/15384101.2014.965072

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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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Authors
Sousa-Victor, P., Perdiguero, E., & Muñoz-Cánoves, P.
Affiliations
Universitat Pompeu Fabra (ES)
Corresponding author
Perdiguero, Eusebio
Venue
Cell Cycle
Published
2014-10-15
Volume
13
Issue
20
Pages
3183-3190
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
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
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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