Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

Steve Horvath; Amin Haghani; Joseph A Zoller; Ken Raj; Ishani Sinha; Todd R Robeck; Pete Black; Aidan Couzens; Clive Lau; Meghety Manoyan; Yadiamaris Aviles Ruiz; Annais Talbott; Katherine Belov; Carolyn J Hogg; Karen E Sears

doi:10.1007/s11357-022-00569-5

Epigenetic clock and methylation studies in marsupials: opossums, Tasmanian devils, kangaroos, and wallabies

Geroscience. 2022 Jun;44(3):1825-1845. doi: 10.1007/s11357-022-00569-5. Epub 2022 Apr 21.

Authors

Steve Horvath^{1

2}, Amin Haghani³, Joseph A Zoller⁴, Ken Raj⁵, Ishani Sinha⁶, Todd R Robeck⁷, Pete Black⁸, Aidan Couzens⁶, Clive Lau⁶, Meghety Manoyan⁶, Yadiamaris Aviles Ruiz⁹, Annais Talbott⁹, Katherine Belov¹⁰, Carolyn J Hogg¹¹, Karen E Sears¹²

Affiliations

¹ Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
² Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
³ Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
⁴ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, UK.
⁶ Department of Ecology and Evolutionary Biology, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
⁷ Zoological Operations, SeaWorld Parks and Entertainment, 8008 SeaWorld Drive, Orlando, FL, USA.
⁸ Busch Gardens Tampa, Tampa, FL, USA.
⁹ Ciencias Naturales, Universidad Interamericana de Puerto Rico, Bayamón, 00958, Puerto Rico.
¹⁰ School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia.
¹¹ School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia. carolyn.hogg@sydney.edu.au.
¹² Department of Ecology and Evolutionary Biology, University of California at Los Angeles, Los Angeles, CA, 90095, USA. ksears@ucla.edu.

Abstract

The opossum (Monodelphis domestica), with its sequenced genome, ease of laboratory care and experimental manipulation, and unique biology, is the most used laboratory marsupial. Using the mammalian methylation array, we generated DNA methylation data from n = 100 opossum samples from the ear, liver, and tail. We contrasted postnatal development and later aging effects in the opossum methylome with those in mouse (Mus musculus, C57BL/6 J strain) and other marsupial species such as Tasmanian devil, kangaroos, and wallabies. While the opossum methylome is similar to that of mouse during postnatal development, it is distinct from that shared by other mammals when it comes to the age-related gain of methylation at target sites of polycomb repressive complex 2. Our immunohistochemical staining results provide additional support for the hypothesis that PRC2 activity increases with later aging in mouse tissues but remains constant in opossum tissues. We present several epigenetic clocks for opossums that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (opossum and human). Two dual-species human-opossum pan-tissue clocks accurately measure chronological age and relative age, respectively. The human-opossum epigenetic clocks are expected to provide a significant boost to the attractiveness of opossum as a biological model. Additional epigenetic clocks for Tasmanian devil, red kangaroos and other species of the genus Macropus may aid species conservation efforts.

Keywords: Aging; DNA methylation; Development; Epigenetic clock; Opossum.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
DNA Methylation*
Epigenesis, Genetic
Epigenomics
Macropodidae* / genetics
Mice
Mice, Inbred C57BL

Grants and funding

R21 OD022988/OD/NIH HHS/United States