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Biological mechanisms of aging predict age-related disease co-occurrence in patients

Fraser, Helen C; Kuan, Valerie; Johnen, Ronja; Zwierzyna, Magdalena; Hingorani, Aroon D; Beyer, Andreas; Partridge, Linda; (2022) Biological mechanisms of aging predict age-related disease co-occurrence in patients. Aging Cell 10.1111/acel.13524. (In press). Green open access

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Abstract

Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co-occurrence of age-related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non-random associations between age-related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age-related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age-related diseases. Mechanisms of aging hence contribute both together and individually to age-related disease co-occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity.

Type: Article
Title: Biological mechanisms of aging predict age-related disease co-occurrence in patients
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/acel.13524
Publisher version: https://doi.org/10.1111/acel.13524
Language: English
Additional information: © 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: age-related disease, aging, aging hallmarks, genetics, multimorbidity
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10145565
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