田纳西大学Robert W. Williams小组取得一项新突破。他们开发出衰老和死亡中遗传和躯体权衡的动力学。该研究于2026年4月22日发表于国际一流学术期刊《自然》杂志上。

在这里，研究组用精算方法绘制了影响死亡率的变异，从6438只青春期老鼠的基础种群开始，到559只活过1100天的幸存者结束。29个Vita基因座影响寿命，具有强烈的年龄和性别特异性效应。大多数人在不同的阶段采取行动，其极性往往随着年龄的增长而逆转，但少数人在一个或两个性别中都有一致的年龄依赖效应。一组单独的30个体细胞位点影响体重和预期寿命之间的相关性。在体型较大的幼鼠中，19个Soma位点介导较高的死亡率，而在体型较大的老年小鼠中，11个位点介导较低的死亡率。所有的影响在雄鼠身上都比在雌鼠身上强。Vita和Soma基因座形成上位网络，严格按性别划分。这些发现为衰老进化理论和分子机制之间提供了一座遗传桥梁，可以指导干预措施延长健康寿命。

据了解，DNA变异在整个生命周期中调节死亡风险，但它们的动态年龄依赖效应尚未在任何物种中得到解决。

附：英文原文

Title: Dynamics of genetic and somatic trade-offs in ageing and mortality

Author: Arends, Danny, Ashbrook, David G., Roy, Suheeta, Lu, Lu, Sloan, Zachary, Centeno, Arthur G., Lamour, Kurt H., de Magalhes, Joo Pedro, Prins, Pjotr, Broman, Karl W., Sen, Saunak, Mitchell, Sarah J., MacArthur, Michael R., Akin, zlem Altintas, Li, Xiaoxu, Bajwa, Amandeep, Diaz, Vivian, Harrison, David E., Strong, Randy, Nelson, James F., Mozhui, Khyobeni, Auwerx, Johan, Williams, Evan G., Miller, Richard A., Williams, Robert W.

Issue&Volume: 2026-04-22

Abstract: DNA variants modulate mortality risks across an entire lifespan but their dynamic age-dependent effects have not been resolved in any species for either sex. Here we mapped variants that shape mortality using an actuarial approach, starting with a base population of 6,438 pubescent mice and ending with 559 survivors that lived beyond 1,100 days of age. Twenty-nine Vita loci influence lifespan with strong age- and sex-specific effects. Most act during distinct stages with polarities that often invert with age, but a minority have consistent age-dependent effects in one or both sexes. A separate set of 30 Soma loci influence correlations between body mass and life expectancy. Nineteen Soma loci mediate higher mortality in larger young mice, whereas 11 mediate lower mortality in larger old mice. All effects are stronger in male mice than in female mice. Vita and Soma loci form epistatic networks split strictly by sex. These findings provide a genetic bridge between evolutionary theories of ageing and molecular mechanisms that can guide interventions to extend healthy lifespan.

DOI: 10.1038/s41586-026-10407-9

Source: https://www.nature.com/articles/s41586-026-10407-9