| Title: | High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan |
| Journal: | Cell Reports |
| Published: | 4 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39368088/ |
| DOI: | https://doi.org/10.1016/j.celrep.2024.114836 |
Publication 13334
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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 C. elegans recombinant inbred advanced intercross 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 correlated positively with developmental time. We validated three longevity modulators, including rict-1, gfm-1, and mltn-1, among the top candidates obtained from multiomics data integration and quantitative trait locus (QTL) mapping. We translated their relevance to humans using UK Biobank data and showed that variants in GFM1 are associated with an elevated risk of age-related heart failure. We organized our dataset as a resource that allows interactive explorations for new longevity targets.</p>
9 Keywords
- Animals
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Humans
- Inbreeding
- Longevity
- Phenotype
- Quantitative Trait Loci
- Transcriptome
17 Authors
- Arwen W Gao
- Gaby El Alam
- Yunyun Zhu
- Weisha Li
- Jonathan Sulc
- Xiaoxu Li
- Elena Katsyuba
- Terytty Y Li
- Katherine A Overmyer
- Amelia Lalou
- Laurent Mouchiroud
- Maroun Bou Sleiman
- Matteo Cornaglia
- Jean-David Morel
- Riekelt H Houtkooper
- Joshua J Coon
- Johan Auwerx
1 Application
| Application ID | Title |
|---|---|
| 48020 | Exploring Diet/Lifestyle/Health factors as causes and modifiers of genetic determinants of healthspan, ageing and longevity |
Enabling scientific discoveries that improve human health