Epigenetic aging and transposon dysregulation reflect size-related lifespan compression in dogs
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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Authors: Blaise L. Mariner, Brianah M. McCoy, Ashlee Greenier, Layla Brassington, Beth Slikas, Christine Adjangba, Claire Cheng, Abbey Marye, Benjamin R. Harrison, Tal Bamberger, Yadid M. Algavi, Efrat Muller, Adam Harris, Emily D. Rout, Cindy Desmarais, Vista Sohrab, Anne C. Avery, Robert M. Seyfarth, Joshua M. Akey, Rozalyn M. Anderson, Elhanan Borenstein, Marta G. Castelhano, Amanda Erickson Coleman, Kate E. Creevy, Matthew D. Dunbar, Virginia R. Fajt, Jessica M. Hoffman, Erica C. Jonlin, Matt R. Kaeberlein, Elinor K. Karlsson, Kathleen F. Kerr, Jing Ma, Evan L. MacLean, Stephanie McGrath, Natasha J. Olby, Daniel Promislow, May J. Reed, Audrey Ruple, Stephen M. Schwartz, Sandi Shrager, Noah Snyder‐Mackler, M. KATHERINE TOLBERT
Institutions: University of Washington, Tufts University, Vanderbilt University, University of Massachusetts Chan Medical School, Arizona State University, Tel Aviv University, Colorado State University, Princeton University, Jean Mayer Human Nutrition Research Center on Aging