Longevity in the Russian Federation: a comprehensive analysis of environmental, socio-economic, clinical, laboratory, and molecular genetic factors

BACKGROUND . A trend toward demographic aging of the population is currently observed in most countries worldwide. More and more people are achieving longevity, both due to environmental factors and lifestyle, as well as to molecular genetic processes. Few large-scale studies have examined all factors contributing to longevity both in Russia and globally. Fewer of them have used a multi-omics approach, which could provide a better insight into the phenomenon of longevity by integrating genomic, epigenomic, transcriptomic and metagenomic data. AIM. To study the longevity phenomenon in the Russian Federation using a comprehensive analysis of lifestyle, environmental, socio-economic, clinical and laboratory factors, as well as molecular genetic factors. MATERIALS AND METHODS . The five-year joint longevity study conducted by the Center for Strategic Planning and the Russian Clinical Research Center for Gerontology has successfully collected one of the world’s largest repositories, containing a unique database of over 20,000 biological samples from 5,000 long-living individuals from 10 regions of the Russian Federation. Each participant undergoes a detailed medical history analysis, a comprehensive geriatric assessment, a wide range of laboratory tests, and molecular genetic testing. RESULTS . An integrated approach to the study of longevity enabled the determination of main aging phenotypes, as well as the environmental and lifestyle factors associated therewith. The longitudinal design of the study also allowed for the identification of factors related to all-cause mortality, including mortality from COVID-19. State-of-the-art sequencing provided an opportunity to examine the molecular genetic factors underlying both longevity (86 genetic variants passed the genome-wide significance threshold for longevity, 2 of which were located in the coding region in the APOE gene) and socially significant geriatric syndromes, such as cognitive impairment (19 genetic variants passed the genome-wide significance threshold, several of which were also located in the APOE gene). The results of the genome-wide association studies have been used in the development of a polygenic score model that enables to assess an early risk for cognitive impairment with 69% accuracy and the longevity probability with 78% accuracy. The results were validated on independent cohorts, as well as in vitro and in vivo models. In addition to the genetic data analysis, the epigenetics of longevity has also been studied. The epigenetic data obtained during the study have enabled the development of a biological age assessment tool with an accuracy of 95%, outperforming other comparable models. CONCLUSIONS . This comprehensive approach, considering both multi-omics and clinical data, could facilitate the development of highly accurate predictive models for aging-associated diseases and biological age assessment models. It provides a better insight into the fundamental mechanisms of longevity and promotes personalized geriatric medicine.