Male hormones accelerate DNA ageing — in sheep, at least

Friday, 30 July, 2021

Male hormones accelerate DNA ageing — in sheep, at least

Most of us are familiar with the fact that women live longer than men, but have you ever thought about why and how this happens?

Researchers from the University of Otago, along with collaborators from the United States, have shown that removal of male hormones in sheep delays ageing of DNA, and that it also drives feminine characteristics of DNA and the chemical tags it holds, known as DNA methylation. Their study has been published in the journal eLife.

“Both farmers and scientists have known for some time that removing male hormones by castration improves longevity compared to their intact counterparts; however, this is the first time anyone has looked at DNA to see if it also ages slower,” said University of Otago PhD student Victoria Sugrue, first-author on the study.

In order to do this, the researchers first had to generate an ‘epigenetic clock’ from large numbers of sheep so they could measure DNA ageing. They then looked at the epigenetic clock of castrated and intact males and found their ‘ticking rate’ is different; meaning that the longer lives of castrated sheep, or ‘wethers’ as they are referred to by farmers, is reflected in their DNA.

Professor Steve Horvath, from the University of California, Los Angeles, is the inventor of the epigenetic clock and a co-author on the study. He explained, “We developed a way to measure biological age in a broad range of mammals — we have looked at over 200 species so far and discovered surprising commonality in which animals age. But the sheep study was unique in that it specifically isolated the effects of male hormones on ageing.”

Dr Tim Hore, research team co-leader and a senior lecturer at Otago, says the study’s findings provide new avenues to understand the mechanism of male-accelerated ageing. “We found that males and females have very different patterns of DNA ageing in sheep; and that despite being male, the castrates (wethers) had very feminine characteristics at specific DNA sites,” he said.

“Interestingly, those sites most affected by castration also bind to receptors of male hormones in humans at a much greater rate than we would expect by chance. This provides a clear link between castration, male hormones and sex-specific differences in DNA ageing.”

In addition to stimulating further understanding about the role of male sex hormones in accelerating ageing, the researchers hope their work will have wider implications. As the first epigenetic clock for sheep, it is possible this work will end up being used to help farmers determine which sheep are going to live longer (and be more productive), or identify meat claiming to be succulent New Zealand lamb, when it is really mutton.

Image caption: Gus the (elderly) castrate at Blackstone Hill Station. Image credit: Dr Tim Hore.

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