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.
Highlights
Aging is a complex process of progressive functional decline influenced by environmental, genetic, and stochastic factors (Lopez-Otin et al, 2013)
Alterations to genome maintenance, inflammation, or proteostasis can result in shortened lifespan and symptoms of rapid aging (Merkwirth et al, 2012; Schleit et al, 2013; Jurk et al, 2014), while genetic, dietary, and pharmacological interventions that reduce growth signaling through IIS, mTOR, and AMPK tend to increase lifespan and delay and reduce the frequency and severity of aging-related pathologies
To focus our analysis on traits that have been sufficiently studied, as well as to address computational limitations in downstream analyses, we chose to restrict our analyses to traits that have been examined in a minimum of five independent genomewide association studies (GWAS), resulting in a total of 410 GWAS in the 5 age-related disease categories
Summary
Aging is a complex process of progressive functional decline influenced by environmental, genetic, and stochastic factors (Lopez-Otin et al, 2013). Genetic approaches to studying aging using yeast, nematode, fly, and rodent models have identified conserved genetic factors that modulate aging (Kenyon, 2010; Vijg & Suh, 2013). Alterations to genome maintenance, inflammation, or proteostasis can result in shortened lifespan and symptoms of rapid aging (Merkwirth et al, 2012; Schleit et al, 2013; Jurk et al, 2014), while genetic, dietary, and pharmacological interventions that reduce growth signaling through IIS, mTOR, and AMPK tend to increase lifespan and delay and reduce the frequency and severity of aging-related pathologies. While the notion that age-related diseases are driven by common underlying pathways of aging is supported by model organism studies (Fig. 1), whether it remains true in human aging is unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
