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Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    by up to 17.6% at the 25% survival timepoint, and reduces age-associated lipofuscin accumulation. This response involves serotonergic GPCR signaling: LSD failed to extend lifespan in\n                    <jats:italic>ser-1<\/jats:italic>\n                    and\n                    <jats:italic>ser-5<\/jats:italic>\n                    mutants and shortened lifespan in\n                    <jats:italic>ser-4<\/jats:italic>\n                    and\n                    <jats:italic>ser-7<\/jats:italic>\n                    mutants, yet remained effective, although with reduced magnitude, in\n                    <jats:italic>tph-1<\/jats:italic>\n                    animals deficient in serotonin synthesis, indicating that endogenous serotonin production is not strictly required. LSD also elicited phenotypes that overlap with CR, including reduced reproductive output, smaller body size, delayed vulval development, and time-dependent remodeling of lipid stores and PHA-4 levels, while adult food-consumption assays detected no reduction in feeding under the conditions tested. Notably, the lifespan benefit was absent in\n                    <jats:italic>eat-2<\/jats:italic>\n                    mutants and was lost under bacterial dilution, where LSD instead shortened lifespan, indicating that nutritional context shapes the response. Transient exposure during early adulthood was sufficient to extend lifespan. Together, these findings identify LSD as a tool to investigate how serotonergic signaling interfaces with conserved longevity-related pathways.\n                  <\/jats:p>","DOI":"10.1007\/s10522-026-10521-1","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:31:32Z","timestamp":1792650692000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lysergic acid diethylamide extends lifespan in Caenorhabditis elegans"],"prefix":"10.1007","volume":"27","author":[{"given":"Beatriz","family":"S. 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GeroScience. https:\/\/doi.org\/10.1007\/S11357-024-01492-7\/METRICS","journal-title":"GeroScience"}],"container-title":["Biogerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10521-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-026-10521-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10522-026-10521-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:31:34Z","timestamp":1792650694000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10522-026-10521-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":49,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["10521"],"URL":"https:\/\/doi.org\/10.1007\/s10522-026-10521-1","relation":{},"ISSN":["1389-5729","1573-6768"],"issn-type":[{"value":"1389-5729","type":"print"},{"value":"1573-6768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"8 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted using\n                      C. elegans\n                      , an invertebrate model. No vertebrate animals were used. All experiments were performed in accordance with relevant institutional guidelines and standard practices for\n                      C. elegans\n                      handling and reporting, with consideration of the ARRIVE guidelines.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"184"}}