Department of Physiopathology, Medical University of Gdansk, 80-211 Gdansk, Poland.
Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, 80-211 Gdansk, Poland.
Int J Mol Sci. 2023 Feb 2;24(3):2888. doi: 10.3390/ijms24032888.
We have shown before that at least one intracellular proteolytic system seems to be at least as abundant in the peripheral blood lymphocytes of centenarians as in the same cells of young individuals (with the cells of the elderly population showing a significant dip compared to both young and centenarian cohorts). Despite scarce published data, in this review, we tried to answer the question how do different types of cells of longevous people-nonagenarians to (semi)supercentenarians-maintain the quality and quantity of their structural and functional proteins? Specifically, we asked if more robust proteodynamics participate in longevity. We hypothesized that at least some factors controlling the maintenance of cellular proteomes in centenarians will remain at the "young" level (just performing better than in the average elderly). In our quest, we considered multiple aspects of cellular protein maintenance (proteodynamics), including the quality of transcribed DNA, its epigenetic changes, fidelity and quantitative features of transcription of both mRNA and noncoding RNAs, the process of translation, posttranslational modifications leading to maturation and functionalization of nascent proteins, and, finally, multiple facets of the process of elimination of misfolded, aggregated, and otherwise dysfunctional proteins (autophagy). We also included the status of mitochondria, especially production of ATP necessary for protein synthesis and maintenance. We found that with the exception of the latter and of chaperone function, practically all of the considered aspects did show better performance in centenarians than in the average elderly, and most of them approached the levels/activities seen in the cells of young individuals.
我们之前已经表明,至少有一种细胞内蛋白水解系统在百岁老人的外周血淋巴细胞中的丰富程度至少与年轻人的相同细胞中的丰富程度相当(与年轻人和百岁老人队列相比,老年人群的细胞表现出明显的下降)。尽管发表的数据很少,但在这篇综述中,我们试图回答一个问题,即长寿人群(非百岁老人到半百岁老人)的不同类型的细胞如何维持其结构和功能蛋白的质量和数量?具体来说,我们想知道是否有更强大的蛋白动态参与了长寿。我们假设,控制百岁老人细胞蛋白质组维持的至少一些因素将保持在“年轻”水平(只是比普通老年人表现得更好)。在我们的探索中,我们考虑了细胞蛋白质维持(蛋白动态)的多个方面,包括转录 DNA 的质量、其表观遗传变化、mRNA 和非编码 RNA 转录的保真度和定量特征、翻译过程、翻译后修饰导致新生蛋白质的成熟和功能化,以及最后,错误折叠、聚集和其他功能失调的蛋白质(自噬)的消除过程的多个方面。我们还包括了线粒体的状态,特别是合成和维持蛋白质所需的 ATP 的产生。我们发现,除了后者和伴侣蛋白功能外,实际上所有被考虑的方面在百岁老人中的表现都比在普通老年人中要好,而且大多数方面都接近年轻人细胞中的水平/活性。