Castration of male sheep eases back DNA maturing

Castration of male sheep eases back DNA maturing


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  • Source: Allen Institute

  • Date: 06 Jul,2021

We all know that women live longer lives than men. If we told you that there were one way to prolong your life, would you listen?

Researchers from University of Otago and collaborators from the United States published a study in ELife today. It showed that castration of male sheep slows down DNA’s aging and also drives female characteristics of DNA and chemical tags, which is known as DNAmethylation.

“Both scientists and farmers have known for some years that castrated male sheep live on an average longer than their intact counterparts. However, this is the first time anyone’s looked at DNA to determine if it also ages faster,” Victoria Sugrue, University of Otago Anatomy PhD Student.

To do this, researchers had to first generate an ‘epigenetic counter’ from large numbers sheep in order to measure DNA aging. The researchers then looked at the epigenetic rates of intact and castrated males. They found that their ticking rate is different, which means that castrated sheep live longer, or ‘wethers, as they are called by farmers.

This study is supported by the rapid development tools for studying DNA aging. It is now possible to determine the age of humans and other mammals by using DNA and epigenetic clocks.

Steve Horvath from the University of California, Los Angeles, is the inventor of the epigenetic clock. He also co-authored the study. The sheep study was the first to isolate the effects of male hormones upon aging.

Dr Tim Hore is a co-leader of the research team and Senior Lecturer at Otago’s Department of Anatomy. He says that the findings of the study provide new avenues for understanding the mechanism of male-accelerated ageing.

“We discovered that males and women have different DNA aging patterns in sheep. Castrates (wethers), despite being males, had very feminine characteristics at certain DNA sites.

“Interestingly, castration affects the most sensitive areas of the body. They also bind to male hormone receptors at a higher rate than we might expect. Dr Hore says this clearly links castration, male hormones, and sex-specific DNA aging differences.

The researchers studied the sex effects of hormones in mice to understand which tissues are most affected. The tissues in which the male hormone receptors can be found (e.g. Large differences in DNA patterns between males and women were observed in tissues containing the male hormone receptors (e.g. skin, kidney, brain). However, tissues without male hormone receptors expression appeared the same in both males and women.

“Most scientists use blood to measure biological age. We did the same for sheep, but it wasn’t blood that we used, but skin. This is where we discovered sex-specific effects on DNA in sheep’s aging. This was also true for mice, where data were available from both males as well as females.

The researchers are hoping their research will lead to wider applications. This work is the first to use epigenetic clocks for sheep. It is possible that this will be used by farmers to determine which sheep live longer and be more productive. Or to identify meat that claims to be New Zealand lamb but is actually mutton.

The University of Otago funded this work as well as the Paul G. Allen Frontiers Group. Funders were not involved in the study design, data collection, interpretation or decision to publish the work. Research materials were made possible by a generous donation from the Central Otago farming communities, Totovision Ltd and the University of Auckland.

The most well-known New Zealand sheep was probably “Shrek”, a Central Otago Merino who managed to evade musterers for six years, and grew a fleece of 27 kg – much larger than the average sheep. Shrek’s discovery and subsequent shearing attracted a lot of media attention, as well as national travel, and visits to the New Zealand parliament and offshore icebergs.

There has been speculation for a long time that Shrek’s mammoth fleece was due to his cleverness in avoiding capture. Also, he was able to survive the cold alpine winters by hiding in caves. Shrek lived to 16 years old after being castrated (wether).

Shrek was 10 years old when he was captured. This is the average age for the longest-lived sheep in a commercial farm. I believe that Shrek’s greatest asset was his long life span – something almost certain to have never happened if he wasn’t castrated,” Dr Hore said.

Journal reference:

Sugrue, V.J., et al. (2021) Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci. eLife.

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