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期刊名称: Human Genetics
Volume:132    Issue:12        Page:1323-1338
ISSN:0340-6717

Genetics of healthy aging and longevity期刊论文

作者: Brooks-Wilson Angela R
DOI:10.1007/s00439-013-1342-z

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页码: 1323-1338
被引频次: 100
出版者: Springer Berlin Heidelberg,SPRINGER,Springer Science & Business Media,Springer
期刊名称: Human Genetics
ISSN: 0340-6717
卷期: Volume:132    Issue:12
语言: English
摘要: Longevity and healthy aging are among the most complex phenotypes studied to date. The heritability of age at death in adulthood is approximately 25 %. Studies of exceptionally long-lived individuals show that heritability is greatest at the oldest ages. Linkage studies of exceptionally long-lived families now support a longevity locus on chromosome 3; other putative longevity loci differ between studies. Candidate gene studies have identified variants at APOE and FOXO3A associated with longevity; other genes show inconsistent results. Genome-wide association scans (GWAS) of centenarians vs. younger controls reveal only APOE as achieving genome-wide significance (GWS); however, analyses of combinations of SNPs or genes represented among associations that do not reach GWS have identified pathways and signatures that converge upon genes and biological processes related to aging. The impact of these SNPs, which may exert joint effects, may be obscured by gene-environment interactions or inter-ethnic differences. GWAS and whole genome sequencing data both show that the risk alleles defined by GWAS of common complex diseases are, perhaps surprisingly, found in long-lived individuals, who may tolerate them by means of protective genetic factors. Such protective factors may ‘buffer’ the effects of specific risk alleles. Rare alleles are also likely to contribute to healthy aging and longevity. Epigenetics is quickly emerging as a critical aspect of aging and longevity. Centenarians delay age-related methylation changes, and they can pass this methylation preservation ability on to their offspring. Non-genetic factors, particularly lifestyle, clearly affect the development of age-related diseases and affect health and lifespan in the general population. To fully understand the desirable phenotypes of healthy aging and longevity, it will be necessary to examine whole genome data from large numbers of healthy long-lived individuals to look simultaneously at both common and rare alleles, with impeccable control for population stratification and consideration of non-genetic factors such as environment.
相关主题: Human Genetics, Gene Function, Molecular Medicine, Biomedicine, Metabolic Diseases, LEUKOCYTE TELOMERE LENGTH, LIFE-SPAN, EXTREME LONGEVITY, GENETICS & HEREDITY, REPLICATION ORIGIN, OLD-AGE, DETECTABLE CLONAL MOSAICISM, LONG-LIVED INDIVIDUALS, GENOME-WIDE ASSOCIATION, EXCEPTIONAL LONGEVITY, APOLIPOPROTEIN-E, Genetic Variation, Genome-Wide Association Study, Health, Life Expectancy, Epigenesis, Genetic, Humans, Aging, Longevity, Gene-Environment Interaction, Genetic Linkage, Preservation, Data processing, Genomes, Single-nucleotide polymorphism, Population genetics, epigenetics, Life span, Apolipoprotein E, chromosome 3, Heritability, Genetic factors, Methylation, Age, FOXO3 protein, Geriatrics, Epigenesis, Genetic - physiology, Aging - genetics, Aging - physiology, Longevity - genetics, Longevity - physiology, Genetic Variation - physiology, Genetic aspects, Apolipoproteins, Analysis, Genomics,

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