Clock presages exciting future

University of Otago anatomy researcher Associate Prof Tim Hore conducts DNA sampling for androgen...
University of Otago anatomy researcher Associate Prof Tim Hore conducts DNA sampling for androgen clock testing. PHOTO: GREGOR RICHARDSON
Yes, it is a clock, but it will not tell you the time of day.

The "androgen clock" is a world-first epigenetic tool that has implications for diagnosing certain medical conditions, detecting sports cheats and the age of meat products.

It was developed by University of Otago researchers who found DNA could be used to predict how long an animal has been exposed to male hormones, otherwise known as androgens.

Lead author and anatomy post-doctoral researcher Dr Victoria Sugrue said high levels of androgen hormone were what made the average male stronger, faster "and hairier" than the average female.

Until now, there had been no way to measure long-term male hormone exposure, she said.

The androgen clock examined specific DNA regions that changed over time in the presence of androgens, and while researchers had not yet been able to create a clock for humans, they were actively working on it because it had exciting potential applications.

One of its uses can be for meat-verification purposes to test if it is tainted, and researchers are also working on a clock for humans which could test for drug cheating in elite sports.

Dr Sugrue said androgens altered DNA over time in a predictable "clock-like" manner and researchers had developed a method to measure it easily.

"We turned the results into a linear model that could estimate months of androgen exposure with surprising accuracy for both mice and sheep.

"Importantly, when we removed the receptor protein from mice that binds to androgens, the androgen clock stopped.

"Moreover, when we gave androgen to females, the clock started ticking again.

"This proves the clock depends on androgens and not some other male factor."

Research team leader and University of Otago anatomy associate professor Tim Hore said researchers had used it to test for tainted meat, by comparing lamb bought from a butcher with old rams from a farm.

"As expected, we showed that meat from the old rams had an androgen clock that was significantly advanced compared to the lamb.

"Meat from older intact male sheep and pigs is likely to be tough and tainted with a bad taste, but that is not always obvious from the shop window."

He said it could also prove meat had been grown with or without hormone supplementation — something particularly important to consumers of beef.

Research to create an androgen clock for humans was now in progress.

"One of the experiments we did was to treat female mice with a synthetic androgen, similar to those used by drug cheats in elite sport.

"It had a striking effect on DNA and accelerated the androgen clock well beyond what we would see in even a male mouse of the same age.

"If we are able to create an androgen clock for humans, it could be used to detect synthetic androgen abuse in elite sports.

"So, if you think about the likes of [Tour de France cyclist] Lance Armstrong, he got caught with instantaneous tests for steroids in his blood at one particular time.

"But once you stop taking it [steroids], it comes down to normal.

"The androgen clock may be able to measure a cumulative effect over time.

"Of course, I'm just speculating because we haven't developed the test, but certainly, we were using very similar hormones in the mice, that you would see in drug testing, like doping studies.

"We could very clearly see that accumulation over time."

He said the same test could also be used in medicine to diagnose hormone disorders such as hyperandrogenism and polycystic ovarian syndrome.

The research was funded by the Royal Society Te Apārangi Marsden Fund and the Health Research Council.

john.lewis@odt.co.nz

 

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