Epigenetic clock and methylation studies in dogs

Abstract

DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging but the principles underpinning them appear to be evolutionarily conserved, as they have now been successfully developed for over 120 mammalian species. Here we describe reliable and highly accurate epigenetic clocks shown to apply to 51 domestic dog breeds. The methylation profiles were generated using a custom array with DNA sequences that are conserved across all mammalian species (HorvathMammalMethylChip40). Canine epigenetic clocks were constructed to estimate age and also predict mortality risk by estimating average time-to-death. We also present two highly accurate human-dog dual species epigenetic clocks (R=0.97), which may facilitate the ready translation from canine to human use (or vice versa) of anti-aging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies herein reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and potentially health status in canines.

Epigenetic predictors of maximum lifespan and other life history traits in mammals

“…We applied it to n=565 blood samples from 51 different breeds 25 . We averaged the predicted maximum lifespan, i.e.…”

Identification of methylation markers for age and Bovine Respiratory Disease in dairy cattle

“…Previous studies of differential methylation in aging have led to the production of epigenetic clocks, for establishing an organisms biological age [8, 62, 63], and identification of age related biological process with differential methylation [64]. In beef cattle, age related hypermethylation was observed in promoter and 5’ UTR regions, with hypomethylation in other regions.…”

Epigenetic clock and methylation studies in gray short-tailed opossums

“…We previously developed dual species clocks for different placental species [32][33][34][35][36][37][38][39][40]. A critical step toward building dual species clocks was the development and use of a mammalian DNA methylation array that profiles CpGs with flanking DNA sequences that are highly conserved across numerous mammalian species.…”

“…DNA methylation-based age estimators have been developed for many mammalian species but not yet for opossums [32][33][34][35][36][37][38][39][40]. Here, we present highly accurate epigenetic clocks that apply to both humans and opossum.…”