Aging disrupts muscle stem cell function by impairing matricellular WISP1 secretion from fibro-adipogenic progenitors
Open accessAbstract
Research on age-related regenerative failure of skeletal muscle has extensively focused on the phenotypes of muscle stem cells (MuSCs). In contrast, the impact of aging on regulatory cells in the MuSC niche remains largely unexplored. Here, we demonstrate that aging impairs the function of mouse fibro-adipogenic progenitors (FAPs) and thereby indirectly affects the myogenic potential of MuSCs. Using transcriptomic profiling, we identify WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as a FAP-derived matricellular signal that is lost during aging. WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling. Transplantation of young FAPs or systemic treatment with WISP1 restores the myogenic capacity of MuSCs in aged mice and rescues skeletal muscle regeneration. Our work establishes that loss of WISP1 from FAPs contributes to MuSC dysfunction in aged skeletal muscles and demonstrates that this mechanism can be targeted to rejuvenate myogenesis.
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Advancing age drives aberrant signaling in FAPs that stimulates profibrotic behavior and skeletal muscle fibrosis, and compromises satellite cell function.
“Advancing age drives aberrant signaling in FAPs that stimulates their profibrotic behavior and skeletal muscle fibrosis, and simultaneously compromises satellite cell function”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Lukjanenko et al., 2019
During ageing, the number of fibroadipogenic progenitors declines, and so does their ability to produce paracrine factors such as WISP1, leading to diminished MuSC support and contributing to the decline in MuSC function.
“During ageing, the number the of fibroadipogenic progenitors declines, and so does their ability to produce paracrine factors such as WNT1-inducible signalling pathway protein 1 (WISP1), a non-structural protein of the ECM10. This leads to diminished MuSC support and contributes to the decline in MuSC function during ageing10.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [10]
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References 60 · Cited by 374
- Authors
- Lukjanenko, L., Karaz, S., Stuelsatz, P., Gurriaran-Rodriguez, U., Michaud, J., Dammone, G., Sizzano, F., Mashinchian, O., Ancel, S., Migliavacca, E., Liot, S., Jacot, G., Metairon, S., Raymond, F., Descombes, P., Palini, A., Chazaud, B., Rudnicki, M. A., Bentzinger, C. F., & Feige, J. N.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Lyon 1 Université (FR)
- University of Ottawa (CA)
- Université de Sherbrooke (CA)
- ORCID
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 24
- Issue
- 3
- Pages
- 433-446.e7
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC6408230
- OpenAlex
- W2912606098
- Cited by
- 374
- References
- 60
- Citations by year
- 2026: 55 · 2025: 48 · 2024: 61 · 2023: 35 · 2022: 53 · 2021: 64 · 2020: 45 · 2019: 13
- FWCI
- 15.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Nestec
- Fondation Suisse de Recherche sur les Maladies Musculaires
- Natural Sciences and Engineering Research Council of Canada
- Fonds de recherche du Québec - Santé
- ThéCell Network
- Canadian Stem Cell Network
- CHUS Foundation
- Banting Research Foundation
- Research Chair of the Centre de recherche médicale de l’Université de Sherbrooke
- NIH (R01AR044031)
- Canadian Institutes of Health Research (FDN-148387)
- Muscular Dystrophy Association
- Stem Cell Network
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- aging, muscle stem cells, fibro-adipogenic progenitors, WISP1, skeletal muscle regeneration, myogenesis, Akt signaling, asymmetric cell division
- MeSH terms
- Aging, Animals, Cells, Cultured, Humans, Mice, Inbred C57BL, Proto-Oncogene Proteins, Stem Cells, Adipocytes, Mice, Knockout, Muscle, Skeletal, Adipogenesis, Mice, CCN Intercellular Signaling Proteins
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