Epigenetic aging and transposon dysregulation reflect size-related lifespan compression in dogs.

Blaise L Mariner, Brianah M McCoy, Ashlee Greenier, Layla Brassington, Elizabeth Slikas, Christine Adjangba, Claire Cheng, Abbey Marye, Benjamin R Harrison, Tal Bamberger, Yadid Algavi, Efrat Muller, Adam Harris, Emily Rout, Cindy Reichel, Vista Sohrab, Elinor Karlsson, Joshua M Akey, Anne C Avery, Elhanan Borenstein, Daniel E L Promislow, Noah Snyder-Mackler, Joshua M Akey, Rozalyn M Anderson, Elhanan Borenstein, Marta G Castelhano, Amanda E Coleman, Kate E Creevy, Matthew D Dunbar, Virginia R Fajt, Jessica M Hoffman, Erica C Jonlin, Matt Kaeberlein, Elinor K Karlsson, Kathleen F Kerr, Jing Ma, Evan L MacLean, Stephanie McGrath, Natasha J Olby, Daniel E L Promislow, May J Reed, Audrey Ruple, Stephen M Schwartz, Sandi Shrager, Noah Snyder-Mackler, M Katherine Tolbert

School of Life Sciences, Arizona State University, Tempe, AZ, USA. · pubmed

Paper

Abstract

The extraordinary lifespan variation in domestic dogs provides a natural experiment for testing how intrinsic rates of biological aging shape lifespan. Using 1640 methylomes from 894 dogs, we developed an epigenetic clock that predicted mortality and demonstrated that epigenetic aging is fastest early in life. At orthologs of human age-associated genes, dogs exhibited concordant age effects on promoter methylation, highlighting conserved remodeling of immune pathways. We found that larger and male dogs, which are shorter lived, exhibit accelerated molecular aging. Distinct epigenetic architectures mediated these effects: Sex-dependent methylation changes were concentrated on the X chromosome, whereas size-associated methylation was especially pronounced at transposable elements (TEs). These findings show that epigenetics reflects lifespan differences in dogs and identifies TEs as potential mediators of size-associated lifespan.

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Research summary

The paper claims that transposable element (TE) dysregulation mediates the accelerated epigenetic aging and lifespan compression observed in larger dog breeds. This is relevant because it identifies a specific molecular mechanism (TEs) linking intrinsic biological aging rates to lifespan variation, providing a testable target for understanding how to slow the rate of aging.

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