van den Akker Erik B, Deelen Joris, Slagboom P Eline, Beekman Marian
Department of Medical Statistics and Bioinformatics, Section of Molecular Epidemiology, Leiden University Medical Center, Postal zone S-05-P, 2300 RC, PO Box 9600, Leiden, Netherlands,
Adv Exp Med Biol. 2015;847:127-39. doi: 10.1007/978-1-4939-2404-2_6.
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.
实足年龄是常见疾病的主要风险因素。因此，人们期望对衰老过程的理解最终将有助于改善老年人群的健康状况。通过确定家族性和超长寿命以及与年龄相关疾病的遗传决定因素，或许可以获得这样的见解。对这些决定因素的研究已在候选基因、全基因组关联研究和连锁研究中展开。由于对基因组常见变异的探索并不能很好地解释衰老和寿命速率的大部分变异，该领域的研究人员直到最近才开始研究罕见遗传变异对这些性状的影响。新一代测序（NGS）通量的增加和成本的降低，已为对候选基因集、全外显子组和个体全基因组进行测序带来了大量新应用。大多数成功的NGS应用仍是针对那些能够轻易识别因果突变的遗传综合征和癌症。在本章中，我们将讨论人类衰老研究的遗传和表型组学方面，以及利用NGS数据来识别与年龄相关疾病和寿命调节相关的基因，并研究生命过程中体细胞遗传变异的积累。
