Fernandes, M;
Wan, C;
Tacutu, R;
Barardo, D;
Rajput, A;
Wang, J;
Thoppil, H;
... de Magalhaes, JP; + view all
(2016)
Systematic analysis of the gerontome reveals links between aging and age-related diseasesSystematic analysis of the gerontome reveals links between aging and age-related diseases.
Human Molecular Genetics
, 25
(21)
pp. 4804-4818.
10.1093/hmg/ddw307.
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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.
| Type: | Article |
|---|---|
| Title: | Systematic analysis of the gerontome reveals links between aging and age-related diseasesSystematic analysis of the gerontome reveals links between aging and age-related diseases |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/hmg/ddw307 |
| Publisher version: | http://dx.doi.org/10.1093/hmg/ddw307 |
| Language: | English |
| Additional information: | © The Author 2016. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Genetics & Heredity, GENES, DATABASE, BIOLOGY, GENEFRIENDS, MECHANISMS, RESOURCES, LONGEVITY, NETWORKS, GENETICS, TARGETS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10047213 |
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