Identifying the genomic determinants of aging and longevity in human population studies: Progress and challenges

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Human lifespan variation is mainly determined by environmental factors, whereas the genetic contribution is 25–30% and expected to be polygenic. Two complementary fields go hand in hand in order to unravel the mechanisms of biological aging: genomic and biomarker research. Explorative and candidate gene studies of the human genome by genetic, transcriptomic, and epigenomic approaches have resulted in the identification of a limited number of interesting positive linkage regions, genes, and pathways that contribute to lifespan variation. The possibilities to further exploit these findings are rapidly increasing through the use of novel technologies, such as next-generation sequencing. Genomic research is progressively being integrated with biomarker studies on aging, including the application of (noninvasive) deep phenotyping and omics data – generated using novel technologies – in a wealth of studies in human populations. Hence, these studies may assist in obtaining a more holistic perspective on the role of the genome in aging and lifespan regulation.

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A review on the accomplishments of genetic, transcriptomic, and epigenetic studies into the biology of aging and longevity by molecular and epidemiological analysis of human populations using family- and population-based study designs. In addition, the development of novel biomarkers of aging and their use for integrated data analysis is discussed.

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