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Updated: Jun 11, 2025
The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan
Published on: June 29, 2018
High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular
Arwen W Gao1, Gaby El Alam2, Yunyun Zhu3
1Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland; Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology, Endocrinology, and Metabolism, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, the Netherlands.
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.
