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Gene-by-environment modulation of lifespan and weight gain in the murine BXD family
Nature Metabolism ( IF 20.8 ) Pub Date : 2021-09-22 , DOI: 10.1038/s42255-021-00449-w
Suheeta Roy 1 , Maroun Bou Sleiman 2 , Pooja Jha 2 , Jesse F Ingels 1 , Casey J Chapman 1 , Melinda S McCarty 1 , Jesse D Ziebarth 1 , Michael Hook 1 , Anna Sun 1 , Wenyuan Zhao 1 , Jinsong Huang 1 , Sarah M Neuner 1 , Lynda A Wilmott 1 , Thomas M Shapaker 1 , Arthur G Centeno 1 , David G Ashbrook 1 , Megan K Mulligan 1 , Catherine C Kaczorowski 3 , Liza Makowski 4 , Yan Cui 1 , Robert W Read 1 , Richard A Miller 5 , Khyobeni Mozhui 6 , Evan G Williams 7 , Saunak Sen 6 , Lu Lu 1 , Johan Auwerx 2 , Robert W Williams 1
Affiliation  

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a low-fat chow diet (CD, n = 663) or a high-fat diet (HFD, n = 685). We further generate key metabolic data in a parallel cohort euthanized at four time points. HFD feeding shortens lifespan by 12%: equivalent to a decade in humans. Initial body weight and early weight gains account for longevity differences of roughly 4–6 days per gram. At 500 days, animals on a HFD typically gain four times as much weight as control, but variation in weight gain does not correlate with lifespan. Classic serum metabolites, often regarded as health biomarkers, are not necessarily strong predictors of longevity. Our data indicate that responses to a HFD are substantially modulated by gene-by-environment interactions, highlighting the importance of genetic variation in making accurate individualized dietary recommendations.



中文翻译:

小鼠 BXD 家族寿命和体重增加的基因-环境调节

寿命和体重如何随着饮食和遗传差异而变化尚不清楚。在这里,我们量化了饮食差异对遗传多样性雌性小鼠家族寿命的影响,将其分为匹配的同基因组,喂食低脂食物(CD,n = 663)或高脂饮食(HFD  ,n  = 685)。我们进一步在四个时间点安乐死的平行队列中生成关键代谢数据。HFD 喂养会使寿命缩短 12%:相当于人类的寿命缩短 10 年。初始体重和早期体重增加导致每克寿命差异大约为 4-6 天。500 天时,服用 HFD 的动物体重通常会增加四倍,但体重增加的变化与寿命无关。经典的血清代谢物通常被视为健康生物标志物,但不一定是长寿的有力预测因子。我们的数据表明,对 HFD 的反应很大程度上受到基因与环境相互作用的调节,这凸显了遗传变异在制定准确的个性化饮食建议方面的重要性。

更新日期:2021-09-22
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