The epigenetic landscape of age-related diseases: the geroscience perspective

Abstract

In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of “geroscience”, which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called “epigenetics clocks” in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.

The biology of frailty in humans and animals: Understanding frailty and promoting translation

“…Variations in DNA methylation patterns occur as methyl groups are either added or removed from position five of cytosine in DNA . There is growing evidence for changes in DNA methylation with age, with most studies supporting the notion that advanced age is associated with global hypomethylation and local hypermethylation . There is now some evidence that changes in DNA methylation are linked to frailty.…”

Chronic stress and body composition disorders: implications for health and disease

“…Physical inactivity, disability, dementia, and metabolic disorders characterized mainly by catabolism are observed in frail aged individuals [95]. Even when adequately nourished, frail aged humans are in a dyshomeostatic state with decrements in body water volume, increased systemic inflammation, decreased anabolism, mitochondrial dysfunction, and DNA disrepair associated with demethylation [96,97].…”

Epigenetic Clocks

“…3 caption) to suggest that the epigenetic clock is a “continuous readout of molecular processes that play a role in development, tissue maintenance and, ultimately, decline.” Given this description, epigenetic clocks are also of interest within the emerging realm of geroscience—an interdisciplinary field that seeks to elucidate basic aging processes in order to strategically combat the wide spectrum of aging‐associated chronic diseases . Although geroscience is focused on a variety of aging‐related molecular and physiological phenomenon (e.g., molecular damage, inflammation, and metabolism), epigenetic clocks are increasingly studied for the role they may play in both the aging process and aging‐related diseases such as cancer and cardiovascular disease, among others …”

“…17 Although geroscience is focused on a variety of aging-related molecular and physiological phenomenon (e.g., molecular damage, inflammation, and metabolism), epigenetic clocks are increasingly studied for the role they may play in both the aging process and aging-related diseases such as cancer and cardiovascular disease, among others. 18 That epigenetic clocks are associated with both developmental processes and aging raises the intriguing question of whether different species have different patterns of clock-like methylation that track chronological and biological age. Studies in other species, so far, reveal phylogenetic differences in age-associated changes in methylation.…”