英国伦敦大学学院Ivana Bjedov、Filipe Cabreiro等研究人员合作发现，增加蛋白质合成的保真性可延长寿命。相关论文于2021年9月14日在线发表在《细胞—代谢》杂志上。

研究人员对RPS23（核糖体解码中心的一个关键蛋白质）的系统发育分析发现，在所有生命领域几乎普遍保守的赖氨酸残基，但在少数嗜热古细菌中被精氨酸取代。当引入真核生物RPS23同源物时，这种突变导致了准确的翻译，以及在酵母、线虫和果蝇中的热休克抗性和更长的寿命。此外，研究人员表明，抗衰老药物如雷帕霉素、Torin1和曲美替尼能减少翻译错误，雷帕霉素能进一步延长RPS23超精确突变体的生物体寿命。这意味着不同的药理抗衰老疗法有统一的作用模式。这些发现为确定新型翻译精确性干预措施来改善衰老铺平了道路。

据悉，蛋白质稳态的丧失是驱动衰老的一个基本过程。蛋白质稳定受到翻译准确性的影响，然而在多细胞生物体衰老过程中，蛋白质合成错误较少的生理后果却不为人所知。

附：英文原文

Title: Increased fidelity of protein synthesis extends lifespan

Author: Victoria Eugenia Martinez-Miguel, Celia Lujan, Tristan Espie--Caullet, Daniel Martinez-Martinez, Saul Moore, Cassandra Backes, Suam Gonzalez, Evgeniy R. Galimov, André E.X. Brown, Mario Halic, Kazunori Tomita, Charalampos Rallis, Tobias von der Haar, Filipe Cabreiro, Ivana Bjedov

Issue&Volume: 2021-09-14

Abstract: Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life, in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies. These findings pave the way for identifying novel translation accuracy interventions to improve aging.

DOI: 10.1016/j.cmet.2021.08.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00417-4