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

View ORCID ProfileSteve Horvath, Amin Haghani, View ORCID ProfileJoseph A. Zoller, Asieh Naderi, Elham Soltanmohammadi, Elena Farmaki, Vimala Kaza, Ioulia Chatzistamou, Hippokratis Kiaris
doi: https://doi.org/10.1101/2021.03.15.435544
Steve Horvath
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA
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  • For correspondence: shorvath@mednet.ucla.edu hk@sc.edu
Amin Haghani
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
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Joseph A. Zoller
2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA
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Asieh Naderi
3Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
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Elham Soltanmohammadi
3Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
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Elena Farmaki
3Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
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Vimala Kaza
4Peromyscus Genetic Stock Center, University of South Carolina, SC, USA
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Ioulia Chatzistamou
5Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, SC, USA
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Hippokratis Kiaris
3Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, SC, USA
4Peromyscus Genetic Stock Center, University of South Carolina, SC, USA
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  • For correspondence: shorvath@mednet.ucla.edu hk@sc.edu
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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 at 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 tissue sources (tail, liver, brain). Two dual species human-peromyscus clocks accurately measure age and relative age defined as the ratio of chronological age to maximum age. These analyses also allowed us to accurately manifest the increasing impact of age, sex, genetic relatedness, and ultimately tissue identity, in that order, in the acquisition of specific methylation patterns in the genome. Genes that were differentially methylated across different biological variables were determined and their potential impact is discussed. This study describes highly accurate DNA methylation-based estimators of age in deer mice and illustrates how differential methylation may be linked to adaptation at different conditions.

Competing Interest Statement

SH is a founder of the non-profit Epigenetic Clock Development Foundation which plans to license several patents from his employer UC Regents. These patents list SH as inventor. The other authors declare no conflicts of interest.

Footnotes

  • ↵# Joint first authorship

  • Emails: shorvath{at}mednet.ucla.edu, ahaghani{at}g.ucla.edu, jaz18{at}g.ucla.edu, ANADERI{at}mailbox.sc.edu, elhams{at}email.sc.edu, efarmaki{at}coh.org, kaza{at}email.sc.edu, chatzistamou{at}uscmed.sc.edu, hk{at}sc.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 16, 2021.
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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
bioRxiv 2021.03.15.435544; doi: https://doi.org/10.1101/2021.03.15.435544
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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
bioRxiv 2021.03.15.435544; doi: https://doi.org/10.1101/2021.03.15.435544

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