Laboratory 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.
Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Cell Rep. 2024 Oct 22;43(10):114836. doi: 10.1016/j.celrep.2024.114836. Epub 2024 Oct 4.
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.
寿命受遗传和环境因素之间复杂相互作用的影响。在具有单一遗传背景的模式生物中研究这些因素，限制了它们在人类中的转化价值。在这里，我们在 85 个秀丽隐杆线虫重组近交系高级互交系（RIAIL）中绘制了寿命决定因素图谱。我们评估了分子谱——转录组、蛋白质组和脂质组——以及生命史特征，包括寿命、发育、生长动态和繁殖。RIAIL 表现出寿命的巨大差异，这与发育时间呈正相关。我们从多组学数据整合和数量性状位点（QTL）图谱中验证了三个长寿调节剂，包括 rict-1、gfm-1 和 mltn-1，作为获得的顶级候选物之一。我们使用英国生物库数据将它们与人类的相关性进行了转化，并表明 GFM1 中的变异与与年龄相关的心力衰竭风险增加有关。我们将我们的数据集组织成一个资源，允许对新的长寿目标进行交互式探索。
