Increased fidelity of protein synthesis extends lifespan.
Increased fidelity of protein synthesis extends lifespan.
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DOI：
10.1016/j.cmet.2021.08.017
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发表时间：
2021-11-02
期刊：
影响因子：
29
通讯作者：
Bjedov I
中科院分区：
文献类型：
--
作者：
Martinez-Miguel VE;Lujan C;Espie-Caullet T;Martinez-Martinez D;Moore S;Backes C;Gonzalez S;Galimov ER;Brown AEX;Halic M;Tomita K;Rallis C;von der Haar T;Cabreiro F;Bjedov I
蛋白质稳态的丧失是驱动衰老的基本过程。蛋白质稳态受翻译准确性的影响，但在多细胞生物衰老过程中蛋白质合成错误较少的生理后果知之甚少。我们对核糖体解码中心的关键蛋白RPS23进行的系统发育分析发现，在所有生命领域中几乎普遍保守的赖氨酸残基在少数极端嗜热古菌中被精氨酸取代。当引入真核RPS23同源物时，这种突变导致酵母、蠕虫和苍蝇中的准确翻译以及热休克抗性和更长的寿命。此外，我们发现抗衰老药物，如雷帕霉素，Torin1和曲美替尼减少翻译错误，雷帕霉素进一步延长了RPS 23超准确突变体的生物体寿命。这意味着不同药理学抗衰老疗法的作用模式是统一的。这些发现为确定新的翻译准确性干预措施以改善衰老铺平了道路。RPS23中进化选择的精氨酸仅存在于超嗜热古菌中。果蝇中的RPS23 K60 R突变导致随着年龄的增长蛋白质合成的准确性提高酵母、蠕虫和果蝇RPS23 K60 R突变体寿命更长、更健康、耐热抗衰老药物雷帕霉素、托林1和曲美替尼增加翻译准确性。证明通过突变核糖体解码中心的单个氨基酸来提高翻译保真度足以改善酵母、蠕虫和苍蝇的健康和寿命。这项工作提供了一个直接的联系之间的错误较少的翻译和长寿。
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. Evolutionarily selected arginine in RPS23 is present only in hyperthermophilic archaea RPS23 K60R mutation in flies leads to improved accuracy of protein synthesis with age Yeast, worm, and fly RPS23 K60R mutants are longer-lived, healthier, and heat resistant Anti-aging drugs, rapamycin, torin1, and trametinib, increase translation accuracy Martinez-Miguel et al. demonstrate that improving translation fidelity by mutating a single amino acid in the decoding center of the ribosome suffices to improve health and longevity in yeast, worms, and flies. This work provides a direct link between fewer errors in translation and longevity.
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影响因子：
9.5
作者：
Katoh K;Rozewicki J;Yamada KD
通讯作者：
Yamada KD
核糖体分析揭示了果蝇果蝇中普遍存在的终止密码子读取。
影响因子：
7.7
作者：
Dunn JG;Foo CK;Belletier NG;Gavis ER;Weissman JS
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作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
29
作者：
Bjedov I;Toivonen JM;Kerr F;Slack C;Jacobson J;Foley A;Partridge L
通讯作者：
Partridge L
影响因子：
16
作者：
Juszkiewicz S;Chandrasekaran V;Lin Z;Kraatz S;Ramakrishnan V;Hegde RS
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Hegde RS