The Genetic Basis for Aging: Much Data, Few Conclusions
As this paper notes, there is a great deal of data regarding genetics and aging, but as yet little in the way of useful conclusions when it comes to applying this knowledge to extend the healthy human life span. From a reductionist point of view, it is clear that genetic differences lie at the root of the large differences in trajectory of aging and life span that are observed between species. The evidence to date suggests that genetic variance within a species has little impact on life span, however. The observe range of life expectancy within a species is mostly a matter of environment and lifestyle. A great deal of funding and effort goes into the continued investigation of the genetics of human longevity, but it isn't at all clear that this will lead to ways to meaningfully extend healthy life span.
The search for key genes of aging and longevity and the study of intracellular signaling pathways can become the basis for the development of methods for diagnosis and correction of conditions that accompany the aging process and for the development of therapeutic methods that increase the duration and quality of life. Numerous studies using model organisms, study of the main mechanisms of cellular aging, large-scale genome-wide association studies in humans, and genetic studies of long livers made it possible to identify various evolutionary conservative metabolic pathways that are similar in various species of organisms and humans, as well as individual genetic loci that affect key traits of human aging and life expectancy.
A significant increase in the life expectancy and the inevitable demographic aging of mankind are pushing researchers to focus more and more on the search for genetic determinants of healthy aging and longevity. In this regard, there is a need to create publicly available high-quality resources with open and integrated databases. Currently, there are already several large resources containing databases of candidate genes and genetic variants associated with human longevity and aging.
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. This 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."