Castration delays DNA aging

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Newswise – Most of us know that women live longer than men. But guys, if we told you that there is one thing that could be done to increase your lifespan, would you?

In a study published today in eLife , researchers at the University of Otago and collaborators in the United States have shown that castration of male sheep delays DNA aging compared to intact males, and that it also determines the female characteristics of the DNA and the chemical tags it contains, known as DNA methylation.

“Farmers and scientists have known for some time that castrated male sheep live on average much longer than their intact counterparts; however, this is the first time that someone has examined DNA to see if it also ages more slowly, ”says study lead author Victoria Sugrue, doctoral student in anatomy at the University of Otago.

To do this, the researchers first had to generate an “epigenetic clock” from a large number of sheep in order to be able to measure DNA aging. They then examined the epigenetic clock of castrated and intact males and found that their “rate of delay” was different; which means that the longer lifespan of castrated sheep, or “wethers” as farmers call them, is reflected in their DNA.

The rapid development of tools to study DNA aging is the basis of this study. Recently, it has become possible to estimate the ages of humans and other mammals using only DNA and epigenetic clocks.

The inventor of the epigenetic clock and co-author of the study, Professor Steve Horvath, of the University of California, Los Angeles explains; “We have developed a way to measure the biological age of a wide range of mammals – we have examined over 200 species so far and found surprising commonalities in the age of the animals. But the study on them sheep was unique in that it specifically isolated the effects of male hormones on aging. ”

Dr Tim Hore, co-leader of the research team and senior lecturer at the Department of Anatomy in Otago, says the study results offer new avenues for understanding the mechanism of accelerated aging in men.

“We found that males and females have very different patterns of DNA aging in sheep; and that although they are males, barrows (wethers) had very feminine characteristics at sites of DNA specific.

“Interestingly, the sites most affected by castration also bind to male hormone receptors in humans at a much higher rate than one might expect by chance. This provides a clear link. between castration, male hormones and sex-specific differences in DNA aging “. Dr Hore said.

To understand which tissues are strongly affected by hormone levels, the researchers looked at the sexual effects in mice. In tissues where male hormone receptors are located (eg, skin, kidney, and brain), large differences between DNA profiles in males and females have been observed. In contrast, tissues without male hormone receptor expression appeared to be identical in males and females.

“Most researchers use blood to measure biological age, and we’ve done this for sheep as well; however, it was not the blood but the skin where we found gender-specific aging effects in sheep DNA. And this also seemed true for the mouse where we had data on many tissues and in both males and females, ”adds Dr. Hore.

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

This work was funded by the University of Otago and the Paul G. Allen Frontiers Group. Donors had no role in the design of the study, the collection and interpretation of the data, or the decision to submit the work for publication. The research material was provided through a generous donation from the farming community of Central Otago, Totovision Ltd, the University of Auckland and the South Australian Research and Development Institute.

SOMETHING TO THINK ABOUT: SHREK the famous NZ wether.

Arguably the most famous New Zealand sheep was “Shrek”, the Central Otago merino who escaped gatherings for 6 years and therefore developed a 27kg fleece – much larger than the average sheep. Shrek’s discovery, and the subsequent shear, sparked great media interest, national trips, and even visits to offshore icebergs and the New Zealand Parliament.

It has long been speculated that the secret to Shrek’s mammoth fleece and its subsequent notoriety was its cunning ability to avoid capture and the fact that it could survive cold Alpine winters by sheltering in caves. But less appreciated is the fact that Shrek was a castrated male (wether), and eventually lived to be 16.

“By the time Shrek was caught he was already 10 years old – roughly the longest-term maximum age of sheep on a commercial farm. I think at least part of Shrek’s fame was just that. he has lived so long – something that almost certainly would not have happened if he had not been neutered, ”said Dr Hore.

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