Genetics of Human Aging

Recent advances in molecular and genetic epidemiology provide us with tools to explore the genetic sources of the variability in humans' biological aging. Genome-wide association study (GWAS) and DNA sequencing have been shown to present an unbiased approach to the identification of new candidate genetic variants and regulatory mechanisms for human diseases. However, successful genetic study of a complex condition such as aging requires clear phenotype definition. Human aging phenotypes have long relied on mortality rate or exceptional longevity; yet, results of GWAS approach focused on longevity are rather insufficient, possibly in part due to the small number of individuals with GWAS data who have reached advanced old age or due to vague phenotype characterization. This poor outcome lands support for a revised approach of phenotype definition, such as “successful” or “healthy” aging, which are potentially more powerful as they can include large number of people with clear clinical relevant. In parallel, a search should continue for essential traits that can refine the characterization of the aging process in humans. Genetic discoveries in human samples should be accompanied by animal-models studies, to bestow insight into the biological mechanisms underlying interindividual differences in susceptibility to (or resistance to) organisms' aging. To become actionable targets, human aging phenotypes need to be assessed many years before death and should be both heritable and validated as predictors of longevity. This might be achieved by integrating multiple traits that share underlying genetic and epigenetic architecture. Knowledge of the key biological mechanisms of aging can inform clinical decisions, which in turn will translate into innovative, diagnostic, and therapeutic interventions to improve the overall health of older individuals.