Exome and whole genome sequencing in aging and longevity

Calendar age is the major risk factor for common disease. It is therefore expected that understanding the aging process will eventually lead to promotion of better health conditions in elderly populations. Such insight may be obtained by identifying the genetic determinants of familial and exceptional longevity and age-related disease. Research of these determinants has been performed in candidate gene, genome-wide association and linkage studies. Because exploration of the common variation in the genome did not explain much of the variation in the rate of aging and longevity, researchers in the field have only recently started to investigate the contribution of rare genetic variants to these traits. The increased throughput and decreased costs of next generation sequencing (NGS) have resulted in a great deal of novel applications for sequencing sets of candidate genes, whole exomes, and whole genomes of individuals. Most of the successful NGS applications are as yet those focused on genetic syndromes and cancers for which causal mutations are readily being identified. In this chapter, we discuss the genetic and phenomic aspects of human aging research and the use of NGS data to identify genes relevant for age-related diseases and lifespan regulation, and to investigate the accumulation of somatic genetic variation during the course of life.