Department of Genome Sciences, University of Washington, Seattle, USA.
J Gerontol A Biol Sci Med Sci. 2021 Sep 13;76(10):1734-1739. doi: 10.1093/gerona/glab015.
The accumulation of protein aggregates and dysfunctional organelles as organisms age has led to the hypothesis that aging involves general breakdown of protein quality control. We tested this hypothesis using a proteomic and informatic approach in the fruit fly Drosophila melanogaster. Turnover of most proteins was markedly slower in old flies. However, ribosomal and proteasomal proteins maintained high turnover rates, suggesting that the observed slowdowns in protein turnover might not be due to a global failure of quality control. As protein turnover reflects the balance of protein synthesis and degradation, we investigated whether decreases in synthesis or decreases in degradation would best explain the observed slowdowns in protein turnover. We found that while many individual proteins in old flies showed slower turnover due to decreased degradation, an approximately equal number showed slower turnover due to decreased synthesis, and enrichment analyses revealed that translation machinery itself was less abundant. Mitochondrial complex I subunits and glycolytic enzymes were decreased in abundance as well, and proteins involved in glutamine-dependent anaplerosis were increased, suggesting that old flies modify energy production to limit oxidative damage. Together, our findings suggest that age-related proteostasis changes in Drosophila represent a coordinated adaptation rather than a system collapse.
随着生物体的衰老，蛋白质聚集体和功能失调的细胞器的积累导致了衰老涉及蛋白质质量控制普遍崩溃的假说。我们在黑腹果蝇 Drosophila melanogaster 中使用蛋白质组学和信息学方法来检验这一假说。在老年果蝇中，大多数蛋白质的周转率明显减慢。然而，核糖体和蛋白酶体蛋白保持着较高的周转率，这表明观察到的蛋白质周转率减慢可能不是由于质量控制的全面失败。由于蛋白质周转率反映了蛋白质合成和降解的平衡，我们研究了合成减少或降解减少是否能最好地解释观察到的蛋白质周转率减慢。我们发现，虽然许多老年果蝇中的单个蛋白质由于降解减少而表现出较慢的周转率，但数量相等的蛋白质由于合成减少而表现出较慢的周转率，并且富集分析表明翻译机制本身的丰度较低。线粒体复合物 I 亚基和糖酵解酶的丰度也降低了，而与谷氨酰胺依赖性氨酰化作用相关的蛋白质增加了，这表明老年果蝇会改变能量产生以限制氧化损伤。总之，我们的研究结果表明，果蝇中与年龄相关的蛋白质稳定性变化代表了一种协调的适应，而不是系统崩溃。
