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DNA methylation age analysis of rapamycin in common marmosets

View ORCID ProfileSteve Horvath, View ORCID ProfileJoseph A. Zoller, Amin Haghani, Ake T. Lu, Ken Raj, Anna J. Jasinska, Julie A. Mattison, Adam B. Salmon
doi: https://doi.org/10.1101/2020.11.21.392779
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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  • ORCID record for Steve Horvath
  • For correspondence: shorvath@mednet.ucla.edu
Joseph A. Zoller
2Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA
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Amin Haghani
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
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Ake T. Lu
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
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Ken Raj
3Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, UK
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Anna J. Jasinska
4Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
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Julie A. Mattison
5Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, USA
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Adam B. Salmon
6The Sam and Ann Barshop Institute for Longevity and Aging Studies, and Department of Molecular Medicine, UT Health San Antonio, and the Geriatric Research Education and Clinical Center, South Texas Veterans Healthcare System, San Antonio TX
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Abstract

Human DNA methylation data have previously been used to develop highly accurate biomarkers of aging (“epigenetic clocks”). Subsequent studies demonstrate that similar epigenetic clocks can also be developed for mice and many other mammals. Here, we describe epigenetic clocks for common marmosets (Callithrix jacchus) based on novel DNA methylation data generated from highly conserved mammalian CpGs that were profiled using a custom Infinium array (HorvathMammalMethylChip40). From these, we developed and present here, two epigenetic clocks for marmosets that are applicable to whole blood samples. We find that the human-marmoset clock for relative age exhibits moderately high age correlations in two other non-human primate species: vervet monkeys and rhesus macaques. In a separate cohort of marmosets, we tested whether intervention with rapamycin, a drug shown to extend lifespan in mice, would alter the epigenetic age of marmosets, as measured by the marmoset epigenetic clocks. These clocks did not detect significant effects of rapamycin on the epigenetic age of marmoset blood. The common marmoset stands out from other mammals in that it is not possible to build accurate estimators of sex based on DNA methylation data: the accuracy of a random forest predictor of sex (66%) was substantially lower than that observed for other mammals (which is close to 100%). Overall, the epigenetic clocks developed here for the common marmoset are expected to be useful for age estimation of wild-born animals and for anti-aging studies in this species.

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 authors

  • Emails: shorvath{at}mednet.ucla.edu, jaz18{at}g.ucla.edu, ahaghani{at}g.ucla.edu, akelu{at}mednet.ucla.edu, ken.raj{at}phe.gov.uk, ankajasinska{at}gmail.com, Julie.mattison{at}nih.gov, salmona{at}uthscsa.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 November 22, 2020.
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DNA methylation age analysis of rapamycin in common marmosets
Steve Horvath, Joseph A. Zoller, Amin Haghani, Ake T. Lu, Ken Raj, Anna J. Jasinska, Julie A. Mattison, Adam B. Salmon
bioRxiv 2020.11.21.392779; doi: https://doi.org/10.1101/2020.11.21.392779
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DNA methylation age analysis of rapamycin in common marmosets
Steve Horvath, Joseph A. Zoller, Amin Haghani, Ake T. Lu, Ken Raj, Anna J. Jasinska, Julie A. Mattison, Adam B. Salmon
bioRxiv 2020.11.21.392779; doi: https://doi.org/10.1101/2020.11.21.392779

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