Exome and Whole Genome Sequencing in Aging and Longevity

Abstract

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.

Differences between biological and chronological age‐at‐death in human skeletal remains: A change of perspective

“…In humans, differences between CA and BA can take place at any stage in life due to genetic and environmental factors (Belsky et al, ; Bline et al, ; Lei et al, ; Liston & Rotroff, ; Mitnitski et al, ; Richmond & Rogol, ; van den Akker, Deelen, Slagboom, & Beekman, ). However, a reliable BA is needed in order to have a valid assessment of an individual's physiological state, which can be interpreted as the global health status (Bae et al, ).…”

The global clonal complexity of the murine blood system declines throughout life and after serial transplantation

“…[4][5][6][7][8][9][10][11][12][13] More than 70% of humans older than 90 years of age display clonal hematopoiesis of indeterminate potential (CHIP; defined as $2% PB from a single cellular clone). [4][5][6][7][8][9][10][11] DNMT3A, TET2, ASXL1, PPM1D, and JAK2 are often mutated in CHIP patients, 6,7 who have a threefold and 11-fold greater risk of developing cardiovascular diseases or leukemia, respectively. 6,11,14 Unknown is how many cellular clones actively contribute to hematopoiesis throughout life and how these numbers change with age.…”

Attitudes towards personal genomics among older Swiss adults: An exploratory study

“…However, they are also characterized by large inter-individual differences in level, rate and direction of change of these characteristics. In the context of genetic research, given their long life history of health and disease, they also represent an extremely rich source of insight into genetic associations with human longevity, as well as genetic associations leading to individual fitness ( van den Akker et al, 2015 , Tan et al, 2006 ).…”