Systematic analysis of the gerontome reveals links between aging and age-related diseases.

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Fernandes, M, Wan, C, Tacutu, R, Barardo, D, Rajput, A, Wang, J, Thoppil, H, Thornton, D ORCID: 0000-0002-4994-2942, Yang, C, Freitas, A et al (show 1 more authors) (2016) Systematic analysis of the gerontome reveals links between aging and age-related diseases. Human molecular genetics, 25 (21). pp. 4804-4818.

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Official URL: https://academic.oup.com/hmg/article/25/21/4804/25...

Abstract

In model organisms, over 2,000 genes have been shown to modulate aging, the collection of which we call the ‘gerontome’. Although some individual aging-related genes have been the subject of intense scrutiny, their analysis as a whole has been limited. In particular, the genetic interaction of aging and age-related pathologies remain a subject of debate. In this work, we perform a systematic analysis of the gerontome across species, including human aging-related genes. First, by classifying aging-related genes as pro- or anti-longevity, we define distinct pathways and genes that modulate aging in different ways. Our subsequent comparison of aging-related genes with age-related disease genes reveals species-specific effects with strong overlaps between aging and age-related diseases in mice, yet surprisingly few overlaps in lower model organisms. We discover that genetic links between aging and age-related diseases are due to a small fraction of aging-related genes which also tend to have a high network connectivity. Other insights from our systematic analysis include assessing how using datasets with genes more or less studied than average may result in biases, showing that age-related disease genes have faster molecular evolution rates and predicting new aging-related drugs based on drug-gene interaction data. Overall, this is the largest systems-level analysis of the genetics of aging to date and the first to discriminate anti- and pro-longevity genes, revealing new insights on aging-related genes as a whole and their interactions with age-related diseases.

Item Type:	Article
Uncontrolled Keywords:	aging, genes, longevity
Depositing User:	Symplectic Admin
Date Deposited:	17 Dec 2020 08:23
Last Modified:	18 Jan 2023 23:06
DOI:	10.1093/hmg/ddw307
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3110561