RT Journal Article
SR Electronic
T1 Epigenetic clock and methylation studies in dogs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.30.437604
DO 10.1101/2021.03.30.437604
A1 Steve Horvath
A1 Ake T. Lu
A1 Amin Haghani
A1 Joseph A. Zoller
A1 Robert T. Brooke
A1 Ken Raj
A1 Jocelyn Plassais
A1 Andrew N. Hogan
A1 Elaine A. Ostrander
YR 2021
UL http://biorxiv.org/content/early/2021/03/30/2021.03.30.437604.abstract
AB 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.Competing Interest StatementSH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. These patents list SH as inventor. Robert T. Brooke is the Executive Director of the Epigenetic Clock Development Foundation. The other authors declare no conflicts of interest.