Predicting 'male-time' with the Androgen Clock

In a study published in the journal Proceedings of the National Academy of Sciences (PNAS), researchers found that DNA can be used to predict how long an animal has been exposed to male hormones, otherwise known as androgens.

To do this, they developed the "Androgen Clock," an analysis platform which examines specific DNA regions that change over time in the presence of androgens.

While researchers have not yet been able to create a clock for humans, they are actively working on it and excited by potential applications.

Lead author Dr Victoria Sugrue, a post-doctoral researcher in the Department of Anatomy, says androgens alter DNA over time in a predictable "clock-like" manner and researchers have 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," Dr Sugrue says.

"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."

High levels of androgen hormone are what makes the average male stronger and faster (and hairier) than the average female. Yet, until now there has been no way to measure long-term male hormone exposure.

Associate Professor Tim Hore, research team leader in the Department of Anatomy, says there are many potential applications for the Androgen Clock in medicine, sports, and agriculture, including meat testing, as performed in the study.

Researchers used it to test for tainted meat, 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. This could be used immediately for verification purposes -- 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.

"Likewise, it could prove meat has been grown with or without hormone supplementation -- something particularly important to consumers of beef."

An Androgen Clock for humans is 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," Associate Professor Hore says.

"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 -- unlike most other tests it would rely on the effect that the androgen has on DNA over long periods of time, rather than a single instantaneous measurement of the molecule itself.

"The same test could also be used in medicine to diagnose hormone disorders like hyperandrogenism."

Underpinning the Androgen Clock study is the rapid development of tools to study DNA aging.

The University of Otago team, in collaboration with researchers from Australia and the USA, previously developed the first way to estimate sheep aging using DNA.

Their work was a part of a large international consortium that measured DNA and age from over 200 mammalian species and turned this into mathematic models, known as "epigenetic clocks," that can predict age in any mammals using DNA alone.

"Over the past decade, a huge amount of research has focussed on epigenetic clocks that has already given us much insight into aging and how it can be slowed or accelerated. Nevertheless, we currently have little understanding of how epigenetic clocks themselves actually work," Associate Professor Hore says.

"The Androgen Clock is the first epigenetic age estimator that can be turned on and off by modulating a single chemical, and it does so without fundamentally changing cellular identity. Further experimentation with the Androgen Clock will help us uncover much more about the mechanism of how DNA ages and why."