Genome‐Wide <scp>DNA</scp> Methylation Patterns Predict Age in the Zebra Shark ( <i>Stegostoma tigrinum</i> ) and Provide Insight Into the Evolution of Vertebrate Aging
Epigenomic changes are a hallmark of aging, and DNA methylation (DNAm) has emerged as the most reliable molecular marker of an individual's age. Genome-wide patterns of age-associated hypo- and hypermethylation have been applied to generate predictive models (i.e., "epigenetic clocks") capable of estimating chronological age in an increasingly diverse set of species including many mammals, a few birds, a reptile, and several bony fishes. Elasmobranchs (sharks, skates, and rays) are underrepresented in comparative investigations of epigenetic aging despite exhibiting exceptional life history variation, occupying a key basal position in the vertebrate phylogeny, and encompassing a large proportion of threatened species lacking accurate, non-lethal age determination methods. Here, we characterize epigenome-wide aging signals in the zebra shark (Stegostoma tigrinum), a long-lived elasmobranch of conservation concern, from whole-genome enzymatic methyl-sequencing of whole blood. Using a cohort of 51 known-age aquarium-bred individuals, we develop several epigenetic clock models capable of predicting chronological age with a median absolute error of 1.03-1.99 years (3.32%-6.42% of lifespan) based on the methylation status of as few as ten cytosines. We further apply our models to 19 individuals of unknown age originating from the wild. By profiling the broader age-associated methylome we demonstrate that these patterns not only predict age with high accuracy but also exhibit striking similarities in their genomic distributions to those observed in mammals pointing to conservation of the processes underlying epigenetic aging across vertebrates.
Authors
- Benjamin B. Parrott (ORCID: https://orcid.org/0000-0002-2391-2470)
- Alfonso Lopez (ORCID: https://orcid.org/0009-0007-2479-8538)
- Samantha L. Bock (ORCID: https://orcid.org/0000-0002-2124-1490)
- Javier Almunia (ORCID: https://orcid.org/0000-0001-6343-1463)
- Jennifer T. Wyffels (ORCID: https://orcid.org/0000-0003-0680-5419)
- Kady Lyons (ORCID: https://orcid.org/0000-0003-2001-4939)
- Ellen M. Leever (ORCID: https://orcid.org/0000-0001-8851-2278)
- Anne M. Bronikowski (ORCID: https://orcid.org/0000-0001-6432-298X)
- Gisele Montano (ORCID: https://orcid.org/0000-0001-7791-2428)
- Nienke Klerks (ORCID: https://orcid.org/0000-0002-9285-9976)
- Mike Stafford
- Joe OKAMOTO
- Gavin J. P. Naylor (ORCID: https://orcid.org/0000-0002-8731-2626)
- Kate E. Archibald (ORCID: https://orcid.org/0000-0001-6097-9319)
- Lise Watson
- Taylor Hartl
- Dan Peterson
- Jay Hemdal
- Lance Adams
- Chris Spaulding
- Kayla Leyden
- Adrienne Rowland
- Lei Yang
- Savannah Vasey
- Aaron Jeskie
Institutions
- SeaWorld Entertainment (US)
- Biotechnology Institute (US)
- Florida Museum of Natural History (US)
- University of Nevada, Las Vegas (US)
- University of Georgia (US)
- Universidade Politécnica de Lisboa (PT)
- Columbus Zoo and Aquarium (US)
- Savannah River National Laboratory (US)
- Shedd Aquarium (US)
- Minnesota Zoo (US)
- Aquarium of the Pacific (US)
- Florida Aquarium (US)
- Okinawa Churashima Foundation (JP)
- Seacoast Science (United States) (US)
- Fundación A LA PAR (ES)
- National Museum of Marine Biology and Aquarium (TW)
- J.M. Burgerscentrum (NL)
- North Carolina Aquarium (US)
- Sengkang General Hospital (SG)
- Centre for Conservation and Research (LK)
- University of Missouri–Kansas City (US)
- University of Delaware (US)
- Michigan State University (US)
Publication Details
- Journal
- Molecular Ecology
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1111/mec.70326
- Citations
- 1
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 11.47
Funders
- National Science Foundation
- U.S. Department of Energy