Genetic evidence for common pathways in human age‐related diseases

Abstract

Aging is the single largest risk factor for chronic disease. Studies in model organisms have identified conserved pathways that modulate aging rate and the onset and progression of multiple age-related diseases, suggesting that common pathways of aging may influence age-related diseases in humans as well. To determine whether there is genetic evidence supporting the notion of common pathways underlying age-related diseases, we analyzed the genes and pathways found to be associated with five major categories of age-related disease using a total of 410 genomewide association studies (GWAS). While only a small number of genes are shared among all five disease categories, those found in at least three of the five major age-related disease categories are highly enriched for apoliprotein metabolism genes. We found that a more substantial number of gene ontology (GO) terms are shared among the 5 age-related disease categories and shared GO terms include canonical aging pathways identified in model organisms, such as nutrient-sensing signaling, translation, proteostasis, stress responses, and genome maintenance. Taking advantage of the vast amount of genetic data from the GWAS, our findings provide the first direct evidence that conserved pathways of aging simultaneously influence multiple age-related diseases in humans as has been demonstrated in model organisms.

The role and therapeutic potential of melatonin in age‐related ocular diseases

“…The aforementioned diseases share underlying molecular processes of aging and other age‐related diseases. This fact agrees with the study of Johnson and colleagues that demonstrates the influence of common anti‐aging pathways in human age‐related diseases . In fact, these ocular pathologies present the nitro‐oxidative damage, mainly at mitochondrial level, as a major cause .…”

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

“…Interestingly, SNPs located near regulators of senescence and inflammation are particularly associated with diseases of ageing, such as cancer, CVD, and type 2 diabetes, and the strongest association was found with a variant in the CDKN2A gene, which encodes the p16 INK4A protein that is over-expressed in many forms of senescence. These findings were replicated in a meta-analysis that included 410 genome-wide association studies 91,92 . In addition, the variant rs2811712 that is close to the CDKN2A gene was associated with poor physical function in two different cohorts 93 .…”

Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

“…The view that the unhealthy aging trajectory can be traced by investigating patients with the most common ARDs is supported by the consideration that aging is the single largest risk factor for ARD development, and that studies of animal models have identified conserved pathways that modulate both the aging rate and ARD onset (Johnson et al, 2015). …”