性别和年龄依赖性遗传与异质鼠群的长寿相关。
Sex- and age-dependent genetics of longevity in a heterogeneous mouse population.
机构信息
Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland.
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center (UTHSC), Memphis, TN 38163, USA.
出版信息
Science. 2022 Sep 30;377(6614):eabo3191. doi: 10.1126/science.abo3191.
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 , , , , and as conserved longevity genes using life-span experiments.
DNA 变体可调节寿命，为了解健康、疾病和衰老的决定因素提供了线索。通过对干预测试计划（ITP）中的 UM-HET3 小鼠进行分析，我们在第 12 号染色体上检测到一个与性别无关的数量性状基因座（QTL），并鉴定了性别特异性 QTL，其中一些仅在老年小鼠中检测到。在小鼠和人类中发现了生命史和长寿之间的相似关系，这突出了早期获得营养和早期生长的重要性。我们确定了对基因表达具有共同的年龄和性别特异性遗传效应，我们将这些效应与模式生物和人类数据相结合，创建了一个假设构建的交互式资源，其中包含优先考虑的长寿和体重基因。最后，我们使用 寿命实验验证了 、 、 、 和 作为保守的长寿基因。
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