Melanie Haiken
10/21/2013 @ 11:15AM
A team of scientists from UCLA have discovered a new biological clock with the potential to measure the age of human tissue. While preliminary, the research has fascinating implications for anti-aging - if it holds up in further testing.
Steve Horvath, a professor of human genetics at the David Geffen School of Medicine at UCLA and of biostatistics at the UCLA Fielding School of Public Health used methylation, a natural process by which DNA are altered over time, to develop an “epigenetic clock” that analyze the effects of age on tissue.
In a study published in the October 21st issue of Genome Biology, Horvath and his team found that women’s breast tissue ages faster than the rest of their bodies and that cancerous tissue is on average 36 years older than other tissue.
Working with more than 8000 samples used in prior research into DNA methylation in human tissue, Horvath and colleagues identified 353 DNA markers from 51 types of cells and tissue (including heart, lungs, brain, liver, cartilage and kidney) that change throughout our lifetimes from before birth through old age.
Together they form a pattern that Horvath used to create a statistical model. The result is a “first-ever accurate age predictor that works across most tissues and cell types,” Horvath says. Horvath has made his calculation methods available to colleagues through a software program he developed.
Is There a “Fountain of Youth” Here?
Well, not so fast. So far, the epigenetic clock is simply a statistical model, and it’s much too early to say whether it actually works, says Darryl Shibata , M.D., professor of pathology at the University of Southern California’s Keck School of Medicine, who has reviewed Horvath’s work. Changes in DNA methylation do occur with aging, Shibata says - “It’s another way of saying we fall apart.” But right now, Horvath’s model only tells us that the two things go together, not that one causes the other.
“The general idea that you can read a genome and it reflects the aging process is probably correct,” says Shibata, “But the weakness is that this study doesn’t provide a mechanism, and without a mechanism it’s just a correlation.”
In other words, says Shibata: “No one knows how this clock works yet,” and numerous steps are needed before the epigenetic clock is considered more than a statistical model.
That said, Shibata believes that a test that could determine the biological age of human tissue would have wide-ranging uses. “Right now, as a human, all you have is your birth certificate to tell you how old you are,” says Shibata. But as we’ve all observed in our daily lives, chronological age doesn’t necessarily correlate with biological age. “You can go to a high school class reunion and see that in action,” Shibata says laughing.
Horvath’s clock – if it works – could provide that determination. “In the same way our circadian clocks keep track of hours, this new epigenetic clock keeps track of years,” says Horvath. “Can it be used as an anti-aging tool? That’s an exciting question we need to answer.”
Note: In previous articles for Forbes, I’ve written about more immediate anti-aging breakthroughs, including a common medication with the potential to reverse aging.)
Fast Forward to the Future
This isn’t the first biological clock scientists have used to measure the aging process. For the past 20 years researchers have been looking at the length of telomeres — the “caps” on the ends of chromosomes – as a measure of biological age, and researchers have been working towards developing an age prediction test based on telomere length. But that’s still in the future, and the research hasn’t yet had practical applications in terms of turning back the clock. Horvath’s research is also a long way away from usability, but it points us in an exciting new direction.
In a prior study, another UCLA research team that included Horvath created an age predictor that used saliva samples to determine DNA methylation levels. They then used the test to accurately predict the age of human subjects within five years, with no information other than the saliva sample. The scientists have already patented the test, which they believe could be used in forensic analysis and by doctors to predict your risk of developing age-related conditions.
The UCLA study published today suggests the possibility “that we could compare the ages of different tissues and organs in the same individual,” Horvath says, with implications for disease diagnosis and treatment. “If we see a drastic acceleration in tissue aging, that would suggest we should start looking for clues to an underlying problem.”
Indeed Neurologist Andrew Levine, another UCLA researcher, an expert in NeuroAIDS, is finding Horvath’s methylation aging marker “highly valuable” in his research studying immune exhaustion and other age-related conditions in relatively young HIV patients. Says Levine, “I think Dr Horvath has discovered something quite important that will hasten our understanding of disease pathogenesis and enable future discovery of effective treatments.”
In addition, Horvath and his colleagues analyzed the biological age of “induced pluripotent” stem cells, which are adult stem cells used in research that have been reprogrammed to a semi embryonic state, and found that the cells now have a biological age of zero. Says Horvath: “It provides proof of concept that one can reset the biological clock.”
If Horvath’s statistical model holds in further testing, it could have wide-ranging applications in aging and anti-aging research. “It could help us to finally understand why we age,” says Horvath. “Right now we have dozens of fairly plausible aging theories. This could be a tool for shedding light on that in a useful way.
Shibata concurs, seeing applications in future research of anti-aging treatments. “If you had a marker of aging that was reliable, you could use it to study aging itself and anti-aging interventions much more effectively.”
As an example, Shibata cites the widely studied theory that calorie restriction can slow the aging process. If we could measure the age of subjects’ tissue before and after a trial of calorie restriction, we could find out if it has an effect. “If the answer is no, we’d be saving people a lot of misery,” he says laughing. “There are hundreds of things that are thought to possibly slow down aging, and if we had a marker we could test them. Imagine the trouble we could save ourselves and how much faster we could figure out what works and what doesn’t.”
http://www.forbes.com/sites/melaniehaiken/2013/10/21/scientists-discover-new-biological-clock-that-measures-aging/2/
