调节寿命的DNA变异提供了对健康、疾病和衰老决定因素的洞察力。通过对干预测试计划（ITP）的UM-HET3小鼠的分析，研究人员在12号染色体上发现了一个与性别无关的定量性状基因座（QTL），并确定了性别特异性QTL，其中一些研究人员只在老年小鼠中发现。在小鼠和人类中发现了生活史和长寿之间的类似关系，这强调了早期获得营养和早期生长的重要性。
研究人员发现了常见的年龄和性别特异性的基因表达影响，并将其与模式生物和人类数据相结合，创建了一个优先考虑长寿和体重基因的假设构建互动资源。最后，研究人员利用线虫的寿命实验验证了Hipk1、Ddost、Hspg2、Fgd6和Pdk1是保守的长寿基因。
附：英文原文
Title: Sex- and age-dependent genetics of longevity in a heterogeneous mouse population
Author: Maroun Bou Sleiman, Suheeta Roy, Arwen W. Gao, Marie C. Sadler, Giacomo V. G. von Alvensleben, Hao Li, Saunak Sen, David E. Harrison, James F. Nelson, Randy Strong, Richard A. Miller, Zoltán Kutalik, Robert W. Williams, Johan Auwerx
Issue&Volume: 2022-09-30
Abstract: DNA variants that modulate life span provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (QTL) on chromosome 12 and identified sex-specific QTLs, some of which we detected only in older mice. Similar relations between life history and longevity were uncovered in mice and humans, underscoring the importance of early access to nutrients and early growth. We identified common age- and sex-specific genetic effects on gene expression that we integrated with model organism and human data to create a hypothesis-building interactive resource of prioritized longevity and body weight genes. Finally, we validated Hipk1, Ddost, Hspg2, Fgd6, and Pdk1 as conserved longevity genes using Caenorhabditis elegans life-span experiments.
DOI: abo3191
Source: https://www.science.org/doi/10.1126/science.abo3191