Translational fidelity and longevity are genetically linked

作者：Boyang Zheng, Weijie Zhang, Gongwang Yu, Wenjun Shi, Shuyun Deng, Xiaoyi Zhang, Jingyu Chen, Ziwei Zhou, Yuyan Shan, Wanting Wu, Erping Long, Xiaoshu Chen, Jian‐Rong Yang · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-62944-y · 被引用次数：5 · 研究领域：Genetics, Aging, and Longevity in Model Organisms、Evolution and Genetic Dynamics、CRISPR and Genetic Engineering

Aging is a series of adverse changes over time that increases mortality risk. Several hypotheses have been proposed to explain aging, including Leslie Orgel's Error-Catastrophe Theory, which asserts that translation errors erode the translational machinery, become self-amplifying, and eventually lead to death. Evidence for the theory is scarce, especially regarding intra-specific fidelity-longevity correlations. Here, we demonstrate that the correlation can be hidden by the constrained evolution of translational fidelity, but remains detectable in long-lived samples. Measuring the lifespan and translational fidelity of a panel of BY × RM yeast recombinant haploid progenies, we validate the fidelity-longevity correlation. QTL analyses reveal that both fidelity and longevity are most strongly associated with a locus encoding vacuolar protein sorting-associated protein 70(VPS70). Replacing VPS70 in BY by its RM allele reduces translation error by ~8.0% and extends lifespan by ~8.9% through a vacuole-dependent mechanism. Our results support the impact of translational fidelity on intra-specific longevity variation.