Oral Presentation ESA-SRB-APEG-NZSE 2022

Androgens and the epigenetic clock (#13)

Victoria J Sugrue 1 , Michael Garratt 1 , Rebecca E Campbell 2 , Timothy A Hore 1
  1. Department of Anatomy, University of Otago, Dunedin, New Zealand
  2. Department of Physiology, University of Otago, Dunedin, New Zealand

Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing disease pathology using only DNA methylation data. We developed the first epigenetic clock for domesticated sheep (Ovis aries), and discovered that castrated male sheep have a decelerated aging rate compared to intact males (Sugrue et al., 2021). We identified several CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Using this data as a starting point, we have created a new methylation clock that can predict male-specific aging with surprising accuracy. Functional experiments using hormonal supplementation suggest the 'ticking-rate' of this clock is dependent upon androgen exposure; a finding that could have implications for reproductive disease diagnosis. 

 

  1. Sugrue, Victoria J., et al. "Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci." Elife 10 (2021): e64932.