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The ins and outs of muscle stem cell aging
Open accessAbstract
Skeletal muscle has a remarkable capacity to regenerate by virtue of its resident stem cells (satellite cells). This capacity declines with aging, although whether this is due to extrinsic changes in the environment and/or to cell-intrinsic mechanisms associated to aging has been a matter of intense debate. Furthermore, while some groups support that satellite cell aging is reversible by a youthful environment, others support cell-autonomous irreversible changes, even in the presence of youthful factors. Indeed, whereas the parabiosis paradigm has unveiled the environment as responsible for the satellite cell functional decline, satellite cell transplantation studies support cell-intrinsic deficits with aging. In this review, we try to shed light on the potential causes underlying these discrepancies. We propose that the experimental paradigm used to interrogate intrinsic and extrinsic regulation of stem cell function may be a part of the problem. The assays deployed are not equivalent and may overburden specific cellular regulatory processes and thus probe different aspects of satellite cell properties. Finally, distinct subsets of satellite cells may be under different modes of molecular control and mobilized preferentially in one paradigm than in the other. A better understanding of how satellite cells molecularly adapt during aging and their context-dependent deployment during injury and transplantation will lead to the development of efficacious compensating strategies that maintain stem cell fitness and tissue homeostasis throughout life.
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“The regenerative capacity of SCs is influenced by both intrinsic modulators and the extrinsic microenvironment13–15.”
From In vivo partial reprogramming of myofibers promotes muscle regeneration by remodeling the stem cell niche (2021) · cites this paper as [15]
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Metadata
- Authors
- Brack, A. S., & Muñoz-Cánoves, P.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Brack, Andrew S.
- ORCID
- Brack, Andrew S.
- Venue
- Skeletal Muscle
- Published
- 2015-12
- Volume
- 6
- Issue
- 1
- Pages
- 1-1
- ISSN
- 2044-5040 (ISSN-L)
- PMC
- PMC4716636
- OpenAlex
- W2271088568
- Cited by
- 166
- References
- 76
- Citations by year
- 2026: 12 · 2025: 11 · 2024: 8 · 2023: 18 · 2022: 17 · 2021: 22 · 2020: 19 · 2019: 19 · 2018: 13 · 2017: 11 · 2016: 16
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Skeletal Muscle (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (RO1AR060868, R01AR061002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- muscle stem cells, satellite cells, aging, skeletal muscle regeneration, parabiosis, stem cell transplantation, extrinsic aging, intrinsic aging, tissue homeostasis, stem cell mobilization
- MeSH terms
- Animals, Cell Differentiation, Humans, Phenotype, Signal Transduction, Cellular Senescence, Muscle, Skeletal, Satellite Cells, Skeletal Muscle, Cell Proliferation, Stem Cell Niche
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