Abstract
AbstractLifespan 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 diverseC. elegansrecombinant 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, includingrict-1,gfm-1andmltn-1. We translated their relevance to humans using UK Biobank data and showed that variants inRICTORandGFM1are 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.
Publisher
Cold Spring Harbor Laboratory
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