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Review
. 2011 Jan 12;366(1561):43-50.
doi: 10.1098/rstb.2010.0259.

Genetics and genomics of human ageing

Affiliations
Review

Genetics and genomics of human ageing

Heather E Wheeler et al. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Ageing in humans is typified by the decline of physiological functions in various organs and tissues leading to an increased probability of death. Some individuals delay, escape or survive much of this age-related decline and live past age 100. Studies comparing centenarians to average-aged individuals have found polymorphisms in genes that are associated with long life, including APOE and FOXOA3, which have been replicated many times. However, the associations found in humans account for small percentages of the variance in lifespan and many other gene associations have not been replicated in additional populations. Therefore, ageing is probably a highly polygenic trait. In humans, it is important to also consider differences in age-related decline that occur within and among tissues. Longitudinal data of age-related traits can be used in association studies to test for polymorphisms that predict how an individual will change over time. Transcriptional and genetic association studies of different tissues have revealed common and unique pathways involved in human ageing. Genomic convergence is a method that combines multiple types of functional genomic information such as transcriptional profiling, expression quantitative trait mapping and gene association. The genomic convergence approach has been used to implicate the gene MMP20 in human kidney ageing. New human genetics technologies are continually in development and may lead to additional breakthroughs in human ageing in the near future.

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Figures

Figure 1.
Figure 1.
The genomic convergence approach. Genes are filtered in each step for those the most likely to be functional. In the first step, a genome-wide transcriptional profile defines genes that show age-related changes in expression. In the second step, SNPs are tested for association with the expression of age-regulated genes. In the final step, the expression quantitative trait loci (eQTLs) are tested for association with a phenotype of ageing (e.g. age-dependent decline in kidney glomerular filtration rate in Wheeler et al. [73]).

References

    1. Oeppen J., Vaupel J. W.2002Demography. Broken limits to life expectancy. Science 296, 1029–103110.1126/science.1069675 (doi:10.1126/science.1069675) - DOI - DOI - PubMed
    1. Wilmoth J. R.1998The future of human longevity: a demographer's perspective. Science 280, 395–39710.1126/science.280.5362.395 (doi:10.1126/science.280.5362.395) - DOI - DOI - PubMed
    1. Sonnega A.2006The future of human life expectancy: have we reached the ceiling or is the sky the limit? Research highlights in the demography and economics of aging 8, 1–4
    1. Herskind A. M., McGue M., Holm N. V., Sorensen T. I., Harvald B., Vaupel J. W.1996The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum. Genet. 97, 319–32310.1007/BF02185763 (doi:10.1007/BF02185763) - DOI - DOI - PubMed
    1. McGue M., Vaupel J. W., Holm N., Harvald B.1993Longevity is moderately heritable in a sample of Danish twins born 1870–1880. J. Gerontol. 48, B237–B244 - PubMed

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