ArticleNature communications2020
Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed.
- Dietary Regulation of Intestinal Stem Cell Function: Nutrient-Sensing, Microbiota-Mediated, and Regenerative Mechanisms from a Dietetic Perspective.Biomedicines · 2026Review
- TNFR1 signaling connects inflammation to impaired fatty acid oxidation to drive intestinal stem cell aging.Nature aging · 2026Article
- Paeonia suffruticosa root bark extract alleviates gut-brain axis dysfunction in DSS-induced colitis via suppression of intestinal necroptosis and glial activation.Inflammopharmacology · 2026Article
- Cellular senescence as a therapeutic target for aging intervention.Biomedical journal · 2026Review
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Article
- Targeting NAT10 alleviates colonic senescence and elderly-onset colitis by disrupting N4-acetylation of DYRK1A.Nature communications · 2026Article
- In vitro modelling of extracellular matrix changes during skin aging: from static 2D to 3D dynamic microphysiological systems.Microsystems & nanoengineering · 2026Review
- Microbiota from young mice restore the function of aged ISCs.Stem cell reports · 2026Article
- Article
- Young cardiac telocyte-derived exosomes rejuvenate aging hearts in rats.Frontiers in cell and developmental biology · 2026Article
- Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging.Aging cell · 2026Article
- The dual role of autophagy in cartilage degradation: from mechanisms to targeted therapeutics.Frontiers in cell and developmental biology · 2026Review
- Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging.PloS one · 2026Article
- ARAF regulates malignant progression of bladder cancer through the p38MAPK pathway.Open medicine (Warsaw, Poland) · 2026Article
- The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine.The journal of headache and pain · 2025Article
- P38α MAPK-induced senescence in cranial suture progenitor cells promotes craniosynostosis.Communications biology · 2025Article
- Muscle homing peptide modified liposomes loaded with EGCG improved skeletal muscle dysfunction by inhibiting inflammation in aging mice.Materials today. Bio · 2025Article
- Immunosenescence and organoids: pathophysiology and therapeutic opportunities.Immunity & ageing : I & A · 2025Review
- The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.Nature communications · 2025Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regulated by mTORC1, a sensor of nutrients and growth factors, which is highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes are recapitulated in intestinal stem cell-specific Tsc1 knockout mice. Mechanistically, mTORC1 activation increases protein synthesis of MKK6 and augments activation of the p38 MAPK-p53 pathway, leading to decreases in the number and activity of intestinal stem cells as well as villus size and density. Targeting p38 MAPK or p53 prevents or rescues ISC and villus aging and nutrient absorption defects. These findings reveal that mTORC1 drives aging by augmenting a prominent stress response pathway in gut stem cells and identify p38 MAPK as an anti-aging target downstream of mTORC1.
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