SREL Reprint #3876

Genome-wide DNA methylation patterns predict age in the zebra shark (Stegostoma tigrinum) and provide insight into the evolution of vertebrate aging

Samantha L. Bock1,2, Kady Lyons3,4, Lei Yang5, Jennifer Wyffels6,7, Lance Adams8, Nienke Klerks9, Aaron Jeskie10, Ellen Leever11, Taylor Hartl12, Javier Almunia13, Dan Peterson14, Ana Ferreira15, Joe Okamoto16, Kate Archibald17, Chris Spaulding18, Kayla Leyden19, Gisele A. Montano20, Savannah Vasey21, Adrienne Rowland22, Lise Watson23, Alfonso Lopez24, Jay Hemdal25, Mike Stafford26, Anne Bronikowski1, Gavin J. P. Naylor5, and Benjamin B. Parrott2,27 

1Department of Integrative Biology, W. K. Kellogg Biological Station, Michigan State University, Hickory Corners, Michigan, USA
2Savannah River Ecology Laboratory, University of Georgia, Aiken, South Carolina, USA
3Georgia Aquarium, Atlanta, Georgia, USA
4Department of Marine Sciences, University of Georgia, Athens, Georgia, USA
5Florida Museum of Natural History, Gainesville, Florida, USA
6Marine Science Research Center, Ripley's Aquariums, Myrtle Beach, South Carolina, USA
7Delaware Biotechnology Institute, University of Delaware, Newark, Delaware, USA
8Aquarium of the Pacific, Long Beach, California, USA
9Burgers' Zoo, Arnhem, the Netherlands
10Columbus Zoo and Aquarium, Powell, Ohio, USA
11Life Sciences Department, Golden Nugget, Las Vegas, Nevada, USA
12Jenkinson's Aquarium, Point Pleasant Beach, New Jersey, USA
13Loro Parque Fundación, Tenerife, Spain
14Minnesota Zoo, Apple Valley, Minnesota, USA
15Oceanario de Lisboa, Lisboa, Portugal
16Okinawa Churaumi Aquarium, Okinawa Churashima Foundation, Okinawa, Japan
17Omaha's Henry Doorly Zoo and Aquarium, Omaha, Nebraska, USA
18Point Defiance Zoo and Aquarium, Tacoma, Washington, USA
19SEA LIFE Kansas City Aquarium, Kansas City, Missouri, USA
20SeaWorld Parks, Orlando, Florida, USA
21SEA LIFE Carlsbad Aquarium, Carlsbad, California, USA
22Shark Reef Aquarium at Mandalay Bay, Las Vegas, Nevada, USA
23John G. Shedd Aquarium, Chicago, Illinois, USA
24Singapore Oceanarium at Resorts World Sentosa, Sentosa Island, Singapore
25Toledo Zoo and Aquarium, Toledo, Ohio, USA
26Wonders of Wildlife National Museum and Aquarium, Springfield, Missouri, USA
27Odum School of Ecology, University of Georgia, Athens, Georgia, USA 

Abstract: 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.

SREL Reprint #3876

Bock, S. L., K. Lyons, L. Yang, J. Wyffels, L. Adams, N. Klerks, A. Jeskie, E. Leever, T. Hartl, J. Almunia, D. Peterson, A. Ferreira, J. Okamoto, K. Archibald, C. Spaulding, K. Leyden, G. A. Montano, S. Vasey, A. Rowland, L. Watson, A. Lopez, J. Hemdal, M. Stafford, A. Bronikowski, G. J. P. Naylor, and B. B. Parrott. 2026. Genome-wide DNA methylation patterns predict age in the zebra shark (Stegostoma tigrinum) and provide insight into the evolution of vertebrate aging. Molecular Ecology 35(e70326).

This information was provided by the University of Georgia's Savannah River Ecology Laboratory (srel.uga.edu).