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Biological mechanisms of aging predict age-related disease multimorbidities in patients

Fraser, HC; Kuan, V; Johnen, R; Zwierzyna, M; Hingorani, AD; Beyer, A; Partridge, L; (2021) Biological mechanisms of aging predict age-related disease multimorbidities in patients. BioRxiv: Cold Spring Harbor, NY, USA. Green open access

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Abstract

Genetic, environmental and pharmacological interventions into the aging process can confer resistance to a multiple age-related diseases in laboratory animals, including rhesus monkeys. These findings imply that mechanisms of aging might contribute to patterns of multimorbidity in humans, and hence could be targeted to prevent multiple 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, 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 signalling pathway and activity of the ERK1/2 pathway played a significant role across multiple aging mechanisms and multiple, diverse age-related diseases. Mechanisms of aging therefore contribute to multiple age-related diseases and to patterns of human age-related multimorbidity, and could potentially be targeted to prevent more than one age-related condition in the same patient.

Type: Working / discussion paper
Title: Biological mechanisms of aging predict age-related disease multimorbidities in patients
Open access status: An open access version is available from UCL Discovery
DOI: 10.1101/2021.05.04.442567
Publisher version: https://doi.org/10.1101/2021.05.04.442567
Language: English
Additional information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10128035
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