Analysis of lifespan across Diversity Outbred mouse studies identifies multiple longevity-associated loci.

IF 3.3 3区生物学 Q2 GENETICS & HEREDITY

Genetics Pub Date : 2025-05-06 DOI:10.1093/genetics/iyaf081

Martin N Mullis, Kevin M Wright, Anil Raj, Daniel M Gatti, Peter C Reifsnyder, Kevin Flurkey, Jonathan R Archer, Laura Robinson, Andrea Di Francesco, Karen L Svenson, Ron Korstanje, David E Harrison, J Graham Ruby, Gary A Churchill

引用次数: 0

Abstract

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conducted a genetic mega-analysis of longevity in Diversity Outbred (DO) mice that included 2,444 animals from three independently conducted lifespan studies. We identified eight loci that contributed significantly to lifespan independently of diet and drug treatment in at least one study. One of these loci also influenced lifespan in a sex-dependent manner, and we detected an additional locus with a diet-specific effect on lifespan. Collectively, these loci explained over half of the estimated heritable variation in lifespan across these studies and provided insight into the genetic architecture of lifespan in DO mice.

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跨多样性的寿命分析近亲繁殖小鼠研究发现了多个与长寿相关的位点。

寿命是一种综合表型，其遗传结构可能突出对健康和衰老有重大影响的多个过程。在这里，我们对多样性近亲繁殖（DO）小鼠的寿命进行了遗传大分析，其中包括来自三个独立进行的寿命研究的2,444只动物。在至少一项研究中，我们发现了8个与饮食和药物治疗无关的显著影响寿命的基因座。其中一个基因座也以性别依赖的方式影响寿命，我们还发现了一个额外的基因座，它对寿命有特定的饮食影响。总的来说，这些基因座解释了这些研究中估计的寿命遗传变异的一半以上，并提供了对DO小鼠寿命遗传结构的深入了解。

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

Genetics GENETICS & HEREDITY-

CiteScore

6.90

自引率

6.10%

发文量

177

审稿时长

1.5 months

期刊介绍： GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.