ArticleNature metabolism2024
Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 52 citations in OpenAlex.
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Maternal methionine supplementation regulates skeletal muscle development through NAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.iScience · 2026Article
- HMGA1-HP1β axis regulates premature aging in Hutchinson-Gilford progeria syndrome through chromatin remodeling.Nature communications · 2026Article
- Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan.Cell metabolism · 2026Article
- The Impact of Ageing on Skeletal Muscle: Roles of Mitochondrial Dysregulation, Systemic Communication, and Exercise.Journal of cellular physiology · 2026Review
- A bioorthogonal nanoconcentrisome system for epigenetic and immunometabolic reprogramming of tissue regeneration in aged female rats.Nature communications · 2026Article
- Enhancers integrate microenvironmental signals in muscle stem cells during regeneration in health, disease, and aging.Skeletal muscle · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Histamine N-methyltransferase upregulation, cardiac hypertrophy, and heart failure.European heart journal · 2026Article
- Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis.Nature aging · 2026Article
- ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- PFKM governs metabolic shifts throughout skeletal muscle differentiation.Nature metabolism · 2026Article
- Cellular survivorship bias as a mechanistic driver of muscle stem cell aging.Science (New York, N.Y.) · 2026Article
- Review
- VDR-Spermidine Axis Protects Against Age-Related Granulosa Cell Dysfunction and Follicular Decline via DNMTs-Mediated p53 Methylation.International journal of biological sciences · 2026Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The global loss of heterochromatin during ageing has been observed in eukaryotes from yeast to humans, and this has been proposed as one of the causes of ageing. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di/tri-methylation and HP1, decrease with age in muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor S-adenosylmethionine (SAM). We find that restoration of intracellular SAM in aged MuSCs restores heterochromatin content to youthful levels and rejuvenates age-associated features, including DNA damage accumulation, increased cell death, and defective muscle regeneration. SAM is not only a methyl group donor for transmethylation, but it is also an aminopropyl donor for polyamine synthesis. Excessive consumption of SAM in polyamine synthesis may reduce its availability for transmethylation. Consistent with this premise, we observe that perturbation of increased polyamine synthesis by inhibiting spermidine synthase restores intracellular SAM content and heterochromatin formation, leading to improvements in aged MuSC function and regenerative capacity in male and female mice. Together, our studies demonstrate a direct causal link between polyamine metabolism and epigenetic dysregulation during murine MuSC ageing.
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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 Socratic graph.