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

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.

Systematic identification of exercise-induced anti-aging processes involving intron retention

“…Aging hallmarks represent the fundamental aspects of aging across nine biological dimensions: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication (López-Otín et al, 2013) (Figure 1A). Previous research has established connections between aging hallmarks and the typical clinical manifestations of aging (Aunan et al, 2016), the co-occurrence of age-related diseases (Fraser et al, 2022), and skeletal muscle-specific aging (Wiedmer et al, 2021). Notably, exercise is posited to influence all aging hallmarks (Garatachea et al, 2015).…”

Flaxseed oil ameliorates aging in d‐galactose induced rats via altering gut microbiota and mitigating oxidative damage

“…Aging is the degenerative changes in various tissues and organs of the organism, and is the result of the combined effects of many pathological and physiological processes. In a sense, aging is not a disease, but it makes the body more susceptible to age-related diseases, 3 such as diabetes, 4 non-alcoholic fatty liver, 5 atherosclerosis, 6 cardiovascular disease 7 and Alzheimer 0 s disease. 4 The free radical theory of aging believes that excessive reactive oxygen species (ROS) production will accelerate the aging process.…”