RESUMO
Healthy human longevity is a global goal of the world health system. Determining the causes and processes influencing human longevity is the primary fundamental goal facing the scientific community. Currently, the main efforts of the scientific community are aimed at identifying the qualitative characteristics of the genome that determine the trait. At the same time, when evaluating qualitative characteristics, there are many challenges that make it difficult to establish associations. Quantitative traits are burdened with such problems to a lesser extent, but they are largely overlooked in current genomic studies of aging and longevity. Although there is a wide repertoire of quantitative trait analyses based on genomic data, most opportunities are ignored by authors, which, along with the inaccessibility of published data, leads to the loss of this important information. This review focuses on describing quantitative traits important for understanding aging and necessary for analysis in further genomic studies, and recommends the inclusion of the described traits in the analysis. The review considers the relationship between quantitative characteristics of the mitochondrial genome and aging, longevity, and age-related neurodegenerative diseases, such as the frequency of extensive mitochondrial DNA (mtDNA) deletions, mtDNA half-life, the frequency of A>G replacements in the mtDNA heavy chain, the number of mtDNA copies; special attention is paid to the mtDNA methylation sign. A separate section of this review is devoted to the correlation of telomere length parameters with age, as well as the association of telomere length with the amount of mitochondrial DNA. In addition, we consider such a quantitative feature as the rate of accumulation of somatic mutations with aging in relation to the lifespan of living organisms. In general, it may be noted that there are quite serious reasons to suppose that various quantitative characteristics of the genome may be directly or indirectly associated with certain aspects of aging and longevity. At the same time, the available data are clearly insufficient for definitive conclusions and the determination of causal relationships.
RESUMO
Aging is a natural process of extinction of the body and the main aspect that determines the life expectancy for individuals who have survived to the post-reproductive period. The process of aging is accompanied by certain physiological, immune, and metabolic changes in the body, as well as the development of age-related diseases. The contribution of genetic factors to human life expectancy is estimated at about 25-30%. Despite the success in identifying genes and metabolic pathways that may be involved in the life extension process in model organisms, the key question remains to what extent these data can be extrapolated to humans, for example, because of the complexity of its biological and sociocultural systems, as well as possible species differences in life expectancy and causes of mortality. New molecular genetic methods have significantly expanded the possibilities for searching for genetic factors of human life expectancy and identifying metabolic pathways of aging, the interaction of genes and transcription factors, the regulation of gene expression at the level of transcription, and epigenetic modifications. The review presents the latest research and current strategies for studying the genetic basis of human aging and longevity: the study of individual candidate genes in genetic population studies, variations identified by the GWAS method, immunogenetic differences in aging, and genomic studies to identify factors of "healthy aging." Understanding the mechanisms of the interaction between factors affecting the life expectancy and the possibility of their regulation can become the basis for developing comprehensive measures to achieve healthy longevity. Supplementary Information: The online version contains supplementary material available at 10.1134/S1022795422120067.
RESUMO
Incubation of primary culture of pulmonary fibroblasts with non-opiate analogue of leuenkephalin (NALE; Phe-D-Ala-Gly-Phe-Leu-Arg, 0.1 µM) reduced generation of superoxide anion-radical (by 20.7%) and decreased the number of p53+ cells (by 40.2%) induced by exposure to H2O2 (60 µM). The cytoprotective effect of NALE was potentiated by NO synthase inhibitor L-NAME (1 mM): the number of p53+ cells decreased by 65.3% and morphometric parameters of the cell nuclei and nucleoli were improved. Incubation of pulmonary fibroblasts culture with peptide G (Phe-D-Ala-Gly-Phe-Leu-Gly, 0.1 µM) also significantly reduced the damaging effect of H2O2: the number of p53+ cells decreased by 73.5%, the area of cell nuclei returned to normal, and generation of superoxide anion-radical decreased by 18.4%. These results indicate that C-terminal amino acid Arg and activation of NO synthase are not involved in the direct cytoprotective effect of NALE.
