ArticleNature aging2021
Sestrin is a key regulator of stem cell function and lifespan in response to dietary amino acids.
Article in Nature aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- Leucine-Restricted Diet Attenuates Small Intestinal Tumorigenesis in ApcFood science & nutrition · 2026Article
- mTOR signaling regulates demand-adapted hematopoiesis and metabolic reprogramming required for an effective cellular immune response in Drosophila melanogaster larvae.PLoS genetics · 2026Article
- Molecular mechanisms underlying the lifespan and healthspan benefits of dietary restriction across species.Frontiers in genetics · 2026Review
- Article
- Nutrient sensing in intestinal stem cell: Linking dietary nutrients to cellular metabolic regulation.World journal of stem cells · 2025Review
- Age mosaic of gut epithelial cells prevents aging.Nature communications · 2025Article
- Protein-responsive gut hormone tachykinin directs food choice and impacts lifespan.Nature metabolism · 2025Article
- Microbiota-derived indole acetic acid extends lifespan through the AhR-Sirt2 pathway inmSystems · 2025Article
- Review
- The gut-adipose/pancreas axis: a novel perspective on glycolipid metabolism dysregulation in MAFLD and T2DM pathogenesis.Frontiers in endocrinology · 2025Review
- Effects of Life-Long Exercise on Age-Related Inflammation, Apoptosis, Oxidative Stress, Ferroptosis Markers, and NRF2/KAEP 1/Klotho Pathway in Rat Kidneys.Physiological research · 2024Article
- Context-dependent impact of the dietary non-essential amino acid tyrosine onScience advances · 2024Article
- Review
- Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion.Nature communications · 2024Article
- Inhibition of S6K lowers age-related inflammation and increases lifespan through the endolysosomal system.Nature aging · 2024Article
- Review
- Article
- Dietary regulation in health and disease.Signal transduction and targeted therapy · 2022Review
- Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine.Science (New York, N.Y.) · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dietary restriction (DR) promotes healthy aging in diverse species. Essential amino acids play a key role, but the molecular mechanisms are unknown. The evolutionarily conserved Sestrin protein, an inhibitor of activity of the target of rapamycin complex 1 (TORC1), has recently been discovered as a sensor of amino acids in vitro. Here, we show that Sestrin null mutant flies have a blunted response of lifespan to DR. A mutant Sestrin fly line, with blocked amino acid binding and TORC1 activation, showed delayed development, reduced fecundity, extended lifespan and protection against lifespan-shortening, high-protein diets. Sestrin mediated reduced intestinal stem cell activity and gut cell turnover from DR, and stem cell proliferation in response to dietary amino acids, by regulating the TOR pathway and autophagy. Sestrin expression in intestinal stem cells was sufficient to maintain gut homeostasis and extend lifespan. Sestrin is thus a molecular link between dietary amino acids, stem cell function and longevity.
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