Longevity, Centenarians and Modified Cellular Proteodynamics

Abstract

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.