| Autor: |
Gao, Arwen W., El Alam, Gaby, Zhu, Yunyun, Li, Weisha, Sulc, Jonathan, Li, Xiaoxu, Katsyuba, Elena, Li, Terytty Y., Overmyer, Katherine A., Lalou, Amelia, Mouchiroud, Laurent, Sleiman, Maroun Bou, Cornaglia, Matteo, Morel, Jean-David, Houtkooper, Riekelt H., Coon, Joshua J., Auwerx, Johan |
| Zdroj: |
Cell Reports; 20240101, Issue: Preprints |
| Abstrakt: |
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 C. 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 three 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 GFM1are associated with an elevated risk of age-related heart failure. We organized our dataset as a resource (https://systems-genetics.org/cel_longevity) that allows interactive explorations for new longevity targets. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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