Males of the majority of species tend to live shorter lives than their female equivalents. This is also true of humans, even when you account for the shortened lifespans of men due to stunts such as – for instance – cementing your head into a microwave for a YouTube video. It's difficult to pick out a single factor for why this gap in life expectancy applies to humans. Lifestyle factors such as men generally smoking and drinking more than women certainly play their part. Hypotheses range from the "unguarded X chromosome" theory – essentially that the smaller male Y chromosome is unable to "hide" an X chromosome that carries mutations that may lead to health threats – to estrogen being protective against certain conditions, decreasing the risk of developing stroke and heart disease. But what if there was a simple way to get some of that time back? A new study suggests there might be, but it may come at a price. Published in the journal eLife, a team from the University of Otago and the University of California took a look at a long-known phenomenon in male sheep. "Both 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 anyone has looked at DNA to see if it also ages slower," first author of the study, Anatomy PhD student Victoria Sugrue said in a statement. The researchers first created an "epigenetic clock" by testing DNA methylation levels – which is a good indicator of biological age and predictor of mortality in later life – using large numbers of sheep. They then compared the methylation levels in castrated and non-castrated males, finding that the castrated males' epigenetic clock "ticks" at a different rate to non-castrated sheep. "We found that males and females have very different patterns of DNA aging in sheep; and that despite being male, the castrates (wethers) had very feminine characteristics at specific DNA sites," research team co-leader and Senior Lecturer at Otago's Department of Anatomy, Dr Tom Hore 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 aging." The team further studied hormone levels and DNA patterns in mice tissues, finding that in places where male hormone receptors are found – such as the skin, kidneys, and brain – there were large differences in DNA aging patterns, which weren't present in tissues without male hormone receptors. "Most researchers use blood for measuring biological age, and we did this for sheep too; however, it was not blood but skin where we found sex-specific aging effects in the DNA of sheep," Dr Hore said. "And this appeared to be also true for mouse where we had data from many tissues and in both males and females." While this research is interesting and furthers our understanding of the effect of male hormones on aging, nobody is suggesting that the solution to living a long healthy life is to castrate all males. More work will be needed to determine if the same effect can be seen in humans. In the meantime, the work could help farmers identify sheep that will live longer. The researchers also made special mention of a legendary sheep Shrek from New Zealand, which went rogue and evaded capture for a full six years. "By the time Shrek was caught he was already 10 years old – roughly the maximum age of the most long-lived sheep on a commercial farm. I think at least part of Shrek's fame was simply that he lived so long – something which almost certainly wouldn't have happened if he was not castrated," Dr Hore says. Source
