High-content phenotypic analysis of a C. elegans recombinant inbred population identifies genetic and molecular regulators of lifespan.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2024-10-22 Epub Date: 2024-10-04 DOI:10.1016/j.celrep.2024.114836

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

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引用次数: 0

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.

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对 elegans 近交系重组种群的高含量表型分析确定了寿命的遗传和分子调控因子。

寿命受遗传和环境因素之间复杂的相互作用的影响。在单一遗传背景的模式生物中研究这些因素限制了它们对人类的转化价值。在这里，我们绘制了 85 个 elegans 重组近交高级杂交品系（RIAILs）的寿命决定因素。我们评估了分子特征（转录组、蛋白质组和脂质组等）和生命史特征，包括寿命、发育、生长动态和繁殖。RIAILs的寿命变化很大，与发育时间呈正相关。我们从多组学数据整合和定量性状基因座（QTL）图谱中获得的顶级候选者中验证了三个长寿调节因子，包括rict-1、gfm-1和mltn-1。我们利用英国生物库数据分析了它们与人类的相关性，结果表明 GFM1 中的变异与年龄相关性心力衰竭风险的升高有关。我们将我们的数据集整理成一个资源，允许对新的长寿目标进行交互式探索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.