Fernandes, M, Wan, C, Tacutu, R, Barardo, D, Rajput, A, Wang, J, Thoppil, H, Thornton, D, 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).
4804 - 4818.
Text
GenAge_patterns_HMG2.docx - Author Accepted Manuscript Download (171kB) |
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: | 10 Feb 2017 10:11 |
Last Modified: | 19 Jan 2023 07:19 |
DOI: | 10.1093/hmg/ddw307 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3005708 |