Universität zu Köln

Fraser, Helen C., Kuan, Valerie, Johnen, Ronja, Zwierzyna, Magdalena, Hingorani, Aroon D., Beyer, Andreas ORCID: 0000-0002-3891-2123 and Partridge, Linda ORCID: 0000-0001-9615-0094 (2022). Biological mechanisms of aging predict age-related disease co-occurrence in patients. Aging Cell, 21 (4). HOBOKEN: WILEY. ISSN 1474-9726

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fraser, Helen C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuan, Valerie UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnen, Ronja UNSPECIFIED UNSPECIFIED UNSPECIFIED Zwierzyna, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Hingorani, Aroon D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyer, Andreas UNSPECIFIED orcid.org/0000-0002-3891-2123 UNSPECIFIED Partridge, Linda UNSPECIFIED orcid.org/0000-0001-9615-0094 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-674884
DOI:	10.1111/acel.13524
Journal or Publication Title:	Aging Cell
Volume:	21
Number:	4
Date:	2022
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1474-9726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGNAL-REGULATED KINASE; MITOCHONDRIAL DYSFUNCTION; ESSENTIAL TREMOR; GENE-EXPRESSION; HALLMARKS; PATHWAY; CANCER; DAMAGE; TARGET Multiple languages Cell Biology; Geriatrics & Gerontology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67488