ArticleAging cell2017
Aging of the skeletal muscle extracellular matrix drives a stem cell fibrogenic conversion.
Article in Aging cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
180 citing papers in PubMed, 234 citations in OpenAlex.
- Severe Muscle Deconditioning Triggers Early Extracellular Matrix Remodeling and Resident Stem Cell Differentiation into Adipocytes in Healthy Men.International journal of molecular sciences · 2022Trial
- The nucleus as a mechanobiological hub in muscle aging.Nucleus (Austin, Tex.) · 2026Review
- Mechanically Regulated Secretion: How Physical Forces Instruct the Secretory Pathway and Remodel the Secretome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- High-Fat Diet-Induced Metabolic Stress Durably Reprograms the Liver Regenerative Compartment Toward a Senescence-Like State.Aging cell · 2026Article
- In Vitro Modeling of Sarcopenia-Related Pathology and Exercise-Associated Adaptations: Integration with In Silico Approaches.International journal of molecular sciences · 2026Review
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- Phase-transition failure in aged skeletal muscle regeneration.Biogerontology · 2026Review
- The Impact of Ageing on Skeletal Muscle: Roles of Mitochondrial Dysregulation, Systemic Communication, and Exercise.Journal of cellular physiology · 2026Review
- Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.Ageing research reviews · 2026Review
- Review
- From Athletic Performance to Functional Ageing: Shared Genetic Architecture, Redox-Inflammatory Pathways and Functional Reserve Across the Life Course-A Narrative Review.Biomedicines · 2026Review
- Age-associated DNA methylation patterns in mouse blood and tail: feasibility of tissue-specific epigenetic clock development.GeroScience · 2026Article
- Musculoskeletal degeneration and cardiovascular aging: a narrative review of shared mechanobiological pathways.Molecular biology reports · 2026Review
- Isolating and Validating Fibroblast-like Cells from the Skeletal Muscle of the Siamese Crocodile (Veterinary sciences · 2026Article
- Article
- An agent-based model suggests how senescent cell behavior and matrix mechanics drive pulmonary fibrosis in aged mice.bioRxiv : the preprint server for biology · 2026Article
- CTLA4-Ig reduces proliferation and inflammatory gene expression in muscle fibroblasts, corresponding to less fibrosis and inflammation inAmerican journal of physiology. Cell physiology · 2026Article
- Mechanobiological landscape of muscle stem cells.Skeletal muscle · 2026Review
- Repeated Disuse Atrophy Imprints a Molecular Memory in Skeletal Muscle: Transcriptional Resilience in Young Adults and Susceptibility in Aged Muscle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
120 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Age-related declines in skeletal muscle regeneration have been attributed to muscle stem cell (MuSC) dysfunction. Aged MuSCs display a fibrogenic conversion, leading to fibrosis and impaired recovery after injury. Although studies have demonstrated the influence of in vitro substrate characteristics on stem cell fate, whether and how aging of the extracellular matrix (ECM) affects stem cell behavior has not been investigated. Here, we investigated the direct effect of the aged muscle ECM on MuSC lineage specification. Quantification of ECM topology and muscle mechanical properties reveals decreased collagen tortuosity and muscle stiffening with increasing age. Age-related ECM alterations directly disrupt MuSC responses, and MuSCs seeded ex vivo onto decellularized ECM constructs derived from aged muscle display increased expression of fibrogenic markers and decreased myogenicity, compared to MuSCs seeded onto young ECM. This fibrogenic conversion is recapitulated in vitro when MuSCs are seeded directly onto matrices elaborated by aged fibroblasts. When compared to young fibroblasts, fibroblasts isolated from aged muscle display increased nuclear levels of the mechanosensors, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ), consistent with exposure to a stiff microenvironment in vivo. Accordingly, preconditioning of young fibroblasts by seeding them onto a substrate engineered to mimic the stiffness of aged muscle increases YAP/TAZ nuclear translocation and promotes secretion of a matrix that favors MuSC fibrogenesis. The findings here suggest that an age-related increase in muscle stiffness drives YAP/TAZ-mediated pathogenic expression of matricellular proteins by fibroblasts, ultimately disrupting MuSC fate.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.