{"doi":"10.1101/2024.01.15.575638","title":"High-content phenotypic analysis of <i>a C. elegans</i> recombinant inbred population identifies genetic and molecular regulators of lifespan","abstract":"Abstract 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 C. elegans recombinant intercross advanced inbred lines (RIAILs). We assessed molecular profiles – transcriptome, proteome, and lipidome – 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 rict-1 , gfm-1 and mltn-1 . We translated their relevance to humans using UK Biobank data and showed that variants in RICTOR and GFM1 are associated with an elevated risk of age-related heart disease, dementia, diabetes, kidney, and liver diseases. We organized our dataset as a resource ( https://lisp-lms.shinyapps.io/RIAILs/ ) that allows interactive explorations for new longevity targets.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9359,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1265684,"name":"Gaby El Alam","orcid":"0000-0002-1396-1332","position":1,"is_corresponding":false},{"id":109567,"name":"Yunyun Zhu","orcid":"0000-0002-0087-3464","position":2,"is_corresponding":false},{"id":1265685,"name":"Weisha Li","orcid":"0000-0002-1370-6067","position":3,"is_corresponding":false},{"id":1265686,"name":"Elena Katsyuba","orcid":"0000-0001-7399-7110","position":4,"is_corresponding":false},{"id":1213262,"name":"Jonathan Sulc","orcid":"0000-0002-5572-6541","position":5,"is_corresponding":false},{"id":1265687,"name":"Terytty Yang Li","orcid":"0000-0003-3684-7935","position":6,"is_corresponding":false},{"id":1213261,"name":"Xiaoxu Li","orcid":"0000-0001-5121-9190","position":7,"is_corresponding":false},{"id":109551,"name":"Katherine A. Overmyer","orcid":"0000-0002-1929-1229","position":8,"is_corresponding":false},{"id":807370,"name":"Amélia Lalou","orcid":null,"position":9,"is_corresponding":false},{"id":1266225,"name":"Laurent Mouchiroud","orcid":null,"position":10,"is_corresponding":false},{"id":461403,"name":"Maroun Bou Sleiman","orcid":"0000-0002-1375-7577","position":11,"is_corresponding":false},{"id":489398,"name":"Matteo Cornaglia","orcid":null,"position":12,"is_corresponding":false},{"id":1265688,"name":"Jean‐David Morel","orcid":"0000-0002-7122-9924","position":13,"is_corresponding":false},{"id":267066,"name":"Riekelt H. Houtkooper","orcid":"0000-0001-9961-0842","position":14,"is_corresponding":false},{"id":71208,"name":"Joshua J. Coon","orcid":"0000-0002-0004-8253","position":15,"is_corresponding":false},{"id":261803,"name":"Johan Auwerx","orcid":"0000-0002-5065-5393","position":16,"is_corresponding":false},{"id":853134,"name":"Arwen W. Gao","orcid":"0000-0001-7687-8926","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:08:28.548530Z","pmid":"38293129","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}