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.

Autoimmunity in centenarians. A paradox

“…Additionally, as will be discussed below, they may have a genetic and epigenetic background that protects them from hyperstimulation. Proteodynamics, defined as the process of regulating the synthesis, modification, and elimination of proteins at the cellular level [ 46 ] is based on an efficient and self-regulated proteostasis signature, which delays or avoids proteostenosis and the establishment of a geroproteome based on proteins with deficient functionality, mutated, leading to the accumulation of residues resistant to proteolytic systems. This implies that, compared to the elderly, centenarians have a more effective DNA maintenance capacity, better transcriptional fidelity, translation with lower error frequency, and a better response to post-translational modifications and autophagy [ 46 ].…”

“… Proteodynamics, defined as the process of regulating the synthesis, modification, and elimination of proteins at the cellular level [ 46 ] is based on an efficient and self-regulated proteostasis signature, which delays or avoids proteostenosis and the establishment of a geroproteome based on proteins with deficient functionality, mutated, leading to the accumulation of residues resistant to proteolytic systems. This implies that, compared to the elderly, centenarians have a more effective DNA maintenance capacity, better transcriptional fidelity, translation with lower error frequency, and a better response to post-translational modifications and autophagy [ 46 ]. In this way, a better cellular and molecular response to stressors would be maintained, avoiding injurious mechanisms to tissues and organs, and delaying oxidation, dysfunction, and cellular aging ( Fig.…”

Gut microbiota in centenarians: A potential metabolic and aging regulator in the study of extreme longevity

“… 28 These studies would aid in understanding precisely how modifiable and nonmodifiable factors impact the organic evolution of centenarians. Cellular senescence, epigenetic clocks, and alterations in stem cells, 29 are some of the cellular and molecular processes that could theoretically reflect cellular proteodynamics, 30 adaptation to aging, 31 and the development of health phenotypes and prognosis during longevity. 32 Having specific data on these mechanisms could facilitate the identification of aging biomarkers for cells, tissues, organs, or diseases, 33 and predict the onset of age‐related chronic diseases.…”

Special Issue “Centenarians—A Model to Study the Molecular Basis of Lifespan and Healthspan 2.0”

“…The primary objective of the review authored by Frankowska et al [17], and published in this S.I., was to explore the role of proteins in the context of longevity. The authors had previously demonstrated the intriguing observation that at least one intracellular proteolytic system exhibited comparable abundance in the peripheral blood lymphocytes of centenarians as that in the same cell type of young individuals [18].…”