Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging

Authors

Pawel Kordowitzki, Nicolaus Copernicus UniversityFollow
Amin Haghani, University of California, Los Angeles
Joseph A. Zoller, University of California, Los Angeles
Caesar Z. Li, University of California, Los Angeles
Ken Raj, Public Health EnglandFollow
Matthew L. Spangler, University of Nebraska - LincolnFollow
Steve Horvath, University of California, Los AngelesFollow

ORCID IDs

Paweł Kordowitzki https://orcid.org/0000-0002-3344-5060

Amin Haghani https://orcid.org/0000-0002-6052-8793

Joseph A. Zoller https://orcid.org/0000-0001-6309-0291

Caesar Z. Li https://orcid.org/0000-0002-3907-7983

Ken Raj https://orcid.org/0000-0002-3744-265X

Matthew L. Spangler https://orcid.org/0000-0001-5184-501X

Steve Horvath https://orcid.org/0000-0002-4110-3589

Date of this Version

2021

Citation

Aging Cell. 2021;20:e13349.

doi:10.1111/acel.13349

Comments

This is an open access article under the terms of the Creative Commons Attribution License,

Abstract

Cattle are an attractive animal model of fertility in women due to their high degree of similarity relative to follicle selection, embryo cleavage, blastocyst formation, and gestation length. To facilitate future studies of the epigenetic underpinnings of aging effects in the female reproductive axis, several DNA methylation-based biomarkers of aging (epigenetic clocks) for bovine oocytes are presented. One such clock was germane to only oocytes, while a dual-tissue clock was highly predictive of age in both oocytes and blood. Dual species clocks that apply to both humans and cattle were also developed and evaluated. These epigenetic clocks can be used to accurately estimate the biological age of oocytes. Both epigenetic clock studies and epigenome-wide association studies revealed that blood and oocytes differ substantially with respect to aging and the underlying epigenetic signatures that potentially influence the aging process. The rate of epigenetic aging was found to be slower in oocytes compared to blood; however, oocytes appeared to begin at an older epigenetic age. The epigenetic clocks for oocytes are expected to address questions in the field of reproductive aging, including the central question: how to slow aging of oocytes.