Methylation studies in Peromyscus: aging, altitude adaptation, and monogamy

Steve Horvath; Amin Haghani; Joseph A Zoller; Asieh Naderi; Elham Soltanmohammadi; Elena Farmaki; Vimala Kaza; Ioulia Chatzistamou; Hippokratis Kiaris

doi:10.1007/s11357-021-00472-5

Methylation studies in Peromyscus: aging, altitude adaptation, and monogamy

Geroscience. 2022 Feb;44(1):447-461. doi: 10.1007/s11357-021-00472-5. Epub 2021 Oct 26.

Authors

Steve Horvath^{1

2}, Amin Haghani³, Joseph A Zoller⁴, Asieh Naderi⁵, Elham Soltanmohammadi⁵, Elena Farmaki⁵, Vimala Kaza⁶, Ioulia Chatzistamou⁷, Hippokratis Kiaris^{8

9}

Affiliations

¹ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
² Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
³ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
⁴ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
⁵ Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA.
⁶ Peromyscus Genetic Stock Center, University of South Carolina, Columbia, SC, USA.
⁷ Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
⁸ Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA. hk@sc.edu.
⁹ Peromyscus Genetic Stock Center, University of South Carolina, Columbia, SC, USA. hk@sc.edu.

Abstract

DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation in Peromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscus clocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude in Peromyscus. The human-Peromyscus epigenetic clocks are expected to provide a significant boost to the attractiveness of Peromyscus as a biological model.

Keywords: Aging; DNA methylation; Deer mouse; Epigenetic clock.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aging / genetics
Altitude
Animals
DNA Methylation
Epigenesis, Genetic*
Peromyscus* / genetics