Epigenetic aging and transposon dysregulation reflect size-related lifespan compression in dogs
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.
Authors
- Yadid M. Algavi (ORCID: https://orcid.org/0000-0001-8127-5070)
- Daniel Promislow (ORCID: https://orcid.org/0000-0001-7088-4495)
- May J. Reed (ORCID: https://orcid.org/0000-0002-6917-9286)
- Brianah M. McCoy (ORCID: https://orcid.org/0000-0003-1988-3248)
- Anne C. Avery (ORCID: https://orcid.org/0000-0002-0163-6495)
- Cindy Desmarais (ORCID: https://orcid.org/0000-0002-6059-0482)
- Kathleen F. Kerr (ORCID: https://orcid.org/0000-0002-6438-9583)
- Sandi Shrager (ORCID: https://orcid.org/0000-0003-0354-9405)
- Amanda Erickson Coleman (ORCID: https://orcid.org/0000-0001-5476-5963)
- Emily D. Rout (ORCID: https://orcid.org/0000-0003-1435-8532)
- Kate E. Creevy (ORCID: https://orcid.org/0000-0003-4169-374X)
- Beth Slikas (ORCID: https://orcid.org/0009-0003-2012-043X)
- Natasha J. Olby (ORCID: https://orcid.org/0000-0003-1349-3484)
- Jessica M. Hoffman (ORCID: https://orcid.org/0000-0002-9487-1629)
- Virginia R. Fajt (ORCID: https://orcid.org/0000-0003-0697-7149)
- Efrat Muller (ORCID: https://orcid.org/0000-0002-0193-0686)
- Noah Snyder‐Mackler (ORCID: https://orcid.org/0000-0003-3026-6160)
- Elinor K. Karlsson (ORCID: https://orcid.org/0000-0002-4343-3776)
- Elhanan Borenstein (ORCID: https://orcid.org/0000-0003-3002-0945)
- Layla Brassington (ORCID: https://orcid.org/0000-0002-9091-7714)
- Matt R. Kaeberlein (ORCID: https://orcid.org/0000-0002-1311-3421)
- Matthew D. Dunbar (ORCID: https://orcid.org/0000-0002-9145-7043)
- Benjamin R. Harrison (ORCID: https://orcid.org/0000-0002-4268-7686)
- Vista Sohrab (ORCID: https://orcid.org/0000-0001-7877-2615)
- Erica C. Jonlin (ORCID: https://orcid.org/0000-0002-1082-0358)
- Evan L. MacLean (ORCID: https://orcid.org/0000-0001-7595-662X)
- Rozalyn M. Anderson (ORCID: https://orcid.org/0000-0002-0864-7998)
- Marta G. Castelhano (ORCID: https://orcid.org/0000-0003-2497-1939)
- Adam Harris (ORCID: https://orcid.org/0000-0002-0700-2098)
- Joshua M. Akey (ORCID: https://orcid.org/0000-0002-4411-1330)
- Tal Bamberger (ORCID: https://orcid.org/0009-0004-2701-4979)
- Blaise L. Mariner (ORCID: https://orcid.org/0000-0002-1387-9347)
- Christine Adjangba (ORCID: https://orcid.org/0009-0009-8512-4355)
- Ashlee Greenier (ORCID: https://orcid.org/0009-0002-4933-9323)
- Abbey Marye (ORCID: https://orcid.org/0009-0003-3375-5610)
- Robert M. Seyfarth (ORCID: https://orcid.org/0000-0003-3026-6160)
- M. KATHERINE TOLBERT
- Stephanie McGrath
- Stephen M. Schwartz
- Audrey Ruple
- Jing Ma
- Claire Cheng (ORCID: https://orcid.org/0009-0000-4675-6768)
Institutions
- Tufts University (US)
- Tel Aviv University (IL)
- University of Massachusetts Chan Medical School (US)
- Vanderbilt University (US)
- Princeton University (US)
- University of Washington (US)
- Jean Mayer Human Nutrition Research Center on Aging (US)
- Arizona State University (US)
- Colorado State University (US)
Publication Details
- Journal
- Science
- Published
- 2026-10-08
- DOI
- https://doi.org/10.1126/science.aeb2986
- Citations
- 1
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 1.94