FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans.
FOXO/DAF-16 Activation Slows Down Turnover of the Majority of Proteins in C. elegans.
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DOI：
10.1016/j.celrep.2016.07.088
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发表时间：
2016-09-13
期刊：
影响因子：
8.8
通讯作者：
Braeckman BP
中科院分区：
文献类型：
--
作者：
Dhondt I;Petyuk VA;Cai H;Vandemeulebroucke L;Vierstraete A;Smith RD;Depuydt G;Braeckman BP
大多数衰老假说假定损伤是累积的，导致逐渐的生理衰退，并最终导致死亡。通过提高周转率来避免蛋白质损伤积累，应该可以减缓衰老过程，延长寿命。然而，降低翻译效率会延长而不是缩短线虫的寿命。我们结合静默(秀丽隐杆线虫的稳定同位素标记)和质谱仪，研究了长寿的daf-2突变体中单个蛋白质的周转。有趣的是，大多数蛋白质在daf-2中表现出延长的半衰期，而其他蛋白质保持不变，这意味着长寿不是由蛋白质的高周转率支持的。这种减速在与翻译相关的蛋白质和线粒体蛋白质中最为明显。相比之下，溶酶体水解酶的高周转率和细胞骨架蛋白的极低周转率基本保持不变。蛋白质动力学的减慢和翻译机制丰度的降低可能表明合成代谢衰减在延长寿命中的重要性，正如超功能理论所表明的那样。Dhondt等人。在秀丽隐杆线虫中应用氮稳定同位素标记(沉默)方法来揭示长寿命胰岛素/胰岛素样生长因子(IGF-1)受体突变体daf-2中的个体蛋白质周转动力学。
Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditis elegans) and mass spectrometry. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, whereas others remained unchanged, signifying that longevity is not supported by high protein turnover. This slowdown was most prominent for translation-related and mitochondrial proteins. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged. The slowdown of protein dynamics and decreased abundance of the translational machinery may point to the importance of anabolic attenuation in lifespan extension, as suggested by the hyperfunction theory. Dhondt et al. apply a stable isotope labeling by nitrogen in Caenorhabditis elegans (SILeNCe) approach to unravel individual protein turnover dynamics in the long-lived insulin/insulin-like growth factor (IGF-1) receptor mutant daf-2.