{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:33:54Z","timestamp":1782920034300,"version":"3.54.5"},"posted":{"date-parts":[[2024,1,16]]},"group-title":"Systems Biology","reference-count":89,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lifespan is influenced by complex interactions between genetic and environmental factors. Studying those factors in model organisms of a single genetic background limits their translational value for humans. Here, we mapped lifespan determinants in 85 genetically diverse\n                  <jats:italic>C. elegans<\/jats:italic>\n                  recombinant intercross advanced inbred lines (RIAILs). We assessed molecular profiles \u2013 transcriptome, proteome, and lipidome \u2013 and life-history traits, including lifespan, development, growth dynamics, and reproduction. RIAILs exhibited large variations in lifespan, which positively correlated with developmental time. Among the top candidates obtained from multi-omics data integration and QTL mapping, we validated known and novel longevity modulators, including\n                  <jats:italic>rict-1<\/jats:italic>\n                  ,\n                  <jats:italic>gfm-1<\/jats:italic>\n                  and\n                  <jats:italic>mltn-1<\/jats:italic>\n                  . We translated their relevance to humans using UK Biobank data and showed that variants in\n                  <jats:italic>RICTOR<\/jats:italic>\n                  and\n                  <jats:italic>GFM1<\/jats:italic>\n                  are associated with an elevated risk of age-related heart disease, dementia, diabetes, kidney, and liver diseases. We organized our dataset as a resource (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/lisp-lms.shinyapps.io\/RIAILs\/\">https:\/\/lisp-lms.shinyapps.io\/RIAILs\/<\/jats:ext-link>\n                  ) that allows interactive explorations for new longevity targets.\n                <\/jats:p>","DOI":"10.1101\/2024.01.15.575638","type":"posted-content","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T15:40:14Z","timestamp":1705419614000},"source":"Crossref","is-referenced-by-count":1,"title":["High-content phenotypic analysis of\n                  <i>a C. elegans<\/i>\n                  recombinant inbred population identifies genetic and molecular regulators of lifespan"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-8926","authenticated-orcid":false,"given":"Arwen 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