Correlating Hallmarks of Aging with Specific Combinations of Comorbidities

Age-related diseases will tend to cluster because they arise from specific underlying processes of aging. If one process of aging is more advanced in a given individual, then that individual is more at risk of suffering the panoply of age-related diseases that are most driven by that process of aging. This is easy enough to say, and seems self-evident. Here, researchers mine human medical databases in order to map clusters of age-related diseases to the hallmarks of aging, visualizing this relationship between mechanisms of aging and disease co-occurrence in real data.

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.


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