ArticleNature communications2021
Saturated very long chain fatty acid configures glycosphingolipid for lysosome homeostasis in long-lived C. elegans.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Lipid elongation as a hallmark of aging.Nature aging · 2026Article
- Discovery of a potential CERS2 inhibitor: hit compound identification via structure-based virtual screening and molecular dynamics simulations.Molecular diversity · 2026Article
- Proteostasis Rebalancing by LET-607 Deficiency Promotes Longevity.Aging cell · 2026Article
- Serum Amino Acid and Fatty Acid Metabolites as Predictors of Sleep Disorders in Children: A Risk Prediction Model.Biomedicines · 2026Article
- The transcription factor SKN-1 drives lysosomal enlargement during aging to maintain function.PLoS biology · 2025Article
- Fluorescence lifetime clocks quantify senescence and aging.Nature aging · 2025Article
- Sphingolipid and methionine metabolism in aging.Journal of cell science · 2025Review
- Different gametogenesis states uniquely impact longevity in Caenorhabditis elegans.Nature communications · 2025Article
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- Lipase-catalyzed interesterification of Sunite sheep tail fat and flaxseed oil provides a fat having a unique fatty acid content and favorable physicochemical and nutritional properties.Food science & nutrition · 2024Article
- Decoding lifespan secrets: the role of the gonad inFrontiers in aging · 2024Review
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- The lipidomes ofAging · 2023Article
- Defining the glucosylceramide population ofFrontiers in physiology · 2023Review
- The impact ofmicroPublication biology · 2023Article
- The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.Nature metabolism · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.
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