Genetic Determinants of Aging and Longevity

Aging is a natural process that all living things have to go through. It is characterized by the gradual loss of function and stability at the molecular, cellular, tissue, and organ levels. This process is often accompanied by the development of age-related diseases, such as cardiovascular disease, musculoskeletal issues, neurodegenerative diseases, and cancer. During the COVID-19 pandemic, the relationship between aging and the immune system became particularly important, as older individuals have a higher risk of developing serious complications and death from the virus compared to younger people. However, there have also been reports of 100-year-old individuals who have successfully survived COVID-19 (some mentioned in our recent paper).

The rate of aging and life expectancy can be influenced by various factors, including genetics, which is believed to account for up to 30% of the variation in human lifespan. It has been found that siblings of people who have lived beyond the age of 105 are 35 times more likely to live to 100 years old than the average population. While progress has been made in identifying genes and metabolic pathways that may be involved in extending the lifespan of model organisms, it is still unclear to what extent these findings can be applied to humans due to the complexity of human biology and society, as well as potential differences in lifespan and causes of mortality between species. 

There are several genes that have been linked to longevity in humans. One such gene is FOXO3A, which is thought to regulate the aging process by controlling cellular stress responses and promoting DNA repair. Another gene, APOE, has been associated with increased risk of age-related diseases such as Alzheimer's disease, but certain variations of the gene have also been linked to increased lifespan. The SIRT1 gene, which is involved in regulating metabolism, has also been linked to longevity in some studies. Other genes that have been associated with increased lifespan include the Lamin A/C gene, the telomere-associated gene TERC, and the P16INK4a gene, which is involved in the regulation of cell cycle progression. There are several large databases of candidate genes associated with human longevity and aging including AgeFactDB, Digital Aging Atlas, AGEMAP, and a set of databases from Human Aging Genomic Resources (HAGR), helping researchers to study the genetics of human aging using modern approaches.

Recent molecular genetic methods have provided new opportunities for studying the genetic basis of human aging and longevity. This includes the examination of individual candidate genes in population studies, variations identified through the GWAS (genome-wide association study) method, differences in immune function related to aging, and genomic studies to identify factors of "healthy aging." By understanding the mechanisms behind the factors that influence lifespan and the possibility of regulating them, it may be possible to develop strategies for achieving healthy longevity.


REFERENCE

Kunizheva SS, Volobaev VP, Plotnikova MY, Kupriyanova DA, Kuznetsova IL, Tyazhelova TV, Rogaev EI. Current Trends and Approaches to the Search for Genetic Determinants of Aging and Longevity. Russ J Genet. 2022;58(12):1427-1443. doi: 10.1134/S1022795422120067. Epub 2022 Dec 28. PMID: 36590179; PMCID: PMC9794410.

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