Translational fidelity and longevity are genetically linked

Boyang Zheng, Weijie Zhang, Gongwang Yu, Wenjun Shi, Shuyun Deng, Xiaoyi Zhang, Jingyu Chen, Ziwei Zhou, Yuyan Shan, Wanting Wu, Erping Long, Xiaoshu Chen () and Jian-Rong Yang ()
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Boyang Zheng: Sun Yat-sen University
Weijie Zhang: Sun Yat-sen University
Gongwang Yu: Guangdong Medical University
Wenjun Shi: Sun Yat-sen University
Shuyun Deng: Sun Yat-sen University
Xiaoyi Zhang: Sun Yat-sen University
Jingyu Chen: Sun Yat-sen University
Ziwei Zhou: Sun Yat-sen University
Yuyan Shan: Sun Yat-sen University
Wanting Wu: Sun Yat-sen University
Erping Long: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoshu Chen: Sun Yat-sen University
Jian-Rong Yang: Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-62944-y

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