The DOI matches its Crossref record; 69 of the 72 references it cites were found in a registry or an index.
Exercise rejuvenates quiescent skeletal muscle stem cells in old mice through restoration of Cyclin D1
Open accessAbstract
Aging impairs tissue repair. This is pronounced in skeletal muscle, whose regeneration by muscle stem cells (MuSCs) is robust in young adult animals but inefficient in older organisms. Despite this functional decline, old MuSCs are amenable to rejuvenation through strategies that improve the systemic milieu, such as heterochronic parabiosis. One such strategy, exercise, has long been appreciated for its benefits on healthspan, but its effects on aged stem cell function in the context of tissue regeneration are incompletely understood. Here we show that exercise in the form of voluntary wheel running accelerates muscle repair in old animals and improves old MuSC function. Through transcriptional profiling and genetic studies, we discovered that the restoration of old MuSC activation ability hinges on restoration of Cyclin D1, whose expression declines with age in MuSCs. Pharmacologic studies revealed that Cyclin D1 maintains MuSC activation capacity by repressing TGFβ signaling. Taken together, these studies demonstrate that voluntary exercise is a practicable intervention for old MuSC rejuvenation. Furthermore, this work highlights the distinct role of Cyclin D1 in stem cell quiescence.
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“Knockdown of cyclin D1 can prevent the exercise-induced enhancement of MuSC function34.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
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In the citing paper
“Notably, structured exercise interventions consisting of endurance training and increasing levels of habitual physical activity have been shown to promote DNA repair pathways as well as resistance to ROS and telomere erosion (Brett et al., 2020; Gomez-Cabrera et al., 2008; Puterman et al., 2010; Radák et al., 2002).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Brett et al., 2020
Experimental — accuracy not yet measuredIn the citing paper
“In 20-month-old mice, 3-weeks of voluntary wheel running rejuvenated satellite cell function and regenerative capacity through restoration of Cyclin D1, a mechanism that may offset senescence initiation through regulation of TGFβ-Smad3 signaling (Brett et al., 2020).”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Brett et al., 2020
In the citing paper
“In muscle, MuSCs also exist as a heterogeneous quiescent population in adult mice30–33, with changes in heterogeneity with ageing32,34,35.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
In the citing paper
“MuSCs enter a deeper state of quiescence with ageing as reflected by their slower kinetics of activation34.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
In the citing paper
“Transcriptional changes in old MuSCs involve metabolic pathways and genes that regulate chromatin accessibility12,34,65.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
In the citing paper
“Exercise has been found to rejuvenate aged MuSCs, in part by reversing the age-dependent increase in cyclin D1 levels to the levels observed in young cells34.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
In the citing paper
“Furthermore, aged MuSC function can be rejuvenated by induction of cyclin D1 expression specifically in those cells34.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
In the citing paper
“Intriguingly, transfer of plasma from exercised aged animals to non-exercised aged animals confers measurable benefits of exercise itself34.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [34]
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Rejuvenation of aged progenitor cells by exposure to a young systemic environment
Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005) · Nature · doi:10.1038/nature03260 · Cited by 2,287
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Ikeda, R., Che, X., Yamaguchi, T., Ushiyama, M., Zheng, C., Okumura, H., Takeda, Y., Shibayama, Y., Nakamura, K. T., Jeung, H., et al. (2005) · Cancer Science · doi:10.1111/j.1349-7006.2005.00057.x · Cited by 2,268
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Control of satellite cell function in muscle regeneration and its disruption in ageing
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Metadata
- Authors
- Brett, J. O., Arjona, M., Ikeda, M., Quarta, M., de Morrée, A., Egner, I. M., Perandini, L. A., Ishak, H. D., Goshayeshi, A., Benjamin, D. I., Both, P., Rodríguez-Mateo, C., Betley, M. J., Wyss-Coray, T., & Rando, T. A.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- University of Oslo (NO)
- Universidade de São Paulo (BR)
- Corresponding author
- Rando, Thomas A.
- ORCID
- Venue
- Nature Metabolism
- Published
- 2020-04-13
- Volume
- 2
- Issue
- 4
- Pages
- 307-317
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC7323974
- OpenAlex
- W3015247821
- Cited by
- 162
- References
- 72
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 21 · 2023: 35 · 2022: 27 · 2021: 18 · 2020: 10
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG036695, AG023806)
- U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR062185)
- 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 › Congenital heart defects research
- Keywords
- skeletal muscle stem cells, physical activity, aging, cyclin D1, TGF-beta signaling, stem cell quiescence, muscle regeneration, voluntary wheel running, heterochronic parabiosis, stem cell rejuvenation, tissue repair
- MeSH terms
- Animals, Cell Separation, Flow Cytometry, Physical Conditioning, Animal, Stem Cells, Cell Transplantation, Muscle, Skeletal, Cyclin D1, Mice
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