Will Horvath’s clock lead to the first effective anti-aging medication?

Evolving science provides more clues than ever before about how the body tracks time

How does the body tell time? It’s one of the mysteries of aging. Without consulting a watch, we’re able to accurately guess whether we’re late for a certain work meeting. We also track time to synchronize our biological processes. We’re born without teeth, and then just as soon as our stomach and intestines have matured to be ready for solid food, hard incisors and canines burst from our gums, to break that solid food into tiny pieces.

So how does the body know? And once we figure that out, can we determine a way to change that time-keeping to suit our purposes? Can we turn back the hands of the body’s biological clock, to allow us to live longer lives?

Biological clock-keeping has been one of the genetic field’s most fascinating areas of research in recent years. A biostatistician from the University of California, Los Angeles, named Steve Horvath, suggested one of the most viable ways to assess the body’s biological clock.

What’s become known as “Horvath’s clock” is based on epigenetics, the study of mechanisms that turn genes on or off, often in response to environmental cues. Everything can have an epigenetic influence; what we eat, the air we breathe, our physical activity. All of it, over time, can cause biochemical modifications to our genes, switching them on or off.

The Body’s Timekeeper

Horvath’s clock reflects the extent and pattern of the genetic switching, which is known as DNA methylation. The mechanism of methylation sees a chemical “tag” placed on a gene to silence it. No tag means the gene can be expressed. DNA methylation plays an important role during normal development, but as we age epigenetic tags can be aberrantly added or removed in response to environmental stressors. The process has been compared to the buildup of rust on a car.

To decide which epigenetic patterns to analyze, Horvath used artificial intelligence to compare the genomes of thousands of different human beings relative to their ages. Then he built a model to calculate a person’s biological age using 353 key sites in their DNA. That method, published in 2013, was able to predict a person’s age within just 2.7 years of their chronological age, according to Nature. Last year, Horvath published a new method that measured genetic methylation at 391 different spots in the genome. This time, the median error was just 1.03 years.

Horvath has also found that certain epigenetic changes occur with age, while others occur in response to environmental exposures, such as smoking. By measuring the pattern and degree of methylation, Dr. Horvath can tell if a person is aging normally, unusually fast, or notably slow. Age acceleration—or faster-than-normal aging—is associated with an increased risk for diseases related to aging. Still another study revealed that the clock can also predict mortality—that is, it can tell us approximately how long a person will live.

What impacts the progression of our epigenetic clock? Not surprisingly, having a family history of longevity works in your favour; it’s estimated that 40% of your clock’s “speed” is inherited from your parents. But the rest comes down to lifestyle and luck.

The good news? Epigenetic changes can be reversed. For example, when someone quits smoking, the epigenetic age improves. Making healthy lifestyle choices appears to slow down the clock’s progression. Eating a healthy diet is associated with slower epigenetic aging, while people with sleep problems experience accelerated epigenetic aging.

Managing expectations

The epigenetic clock is still in its infancy. Although some companies offer epigenetic testing, the clinical utility is still being defined. The hope is these biological studies will help us understand the aging process so that we may one day be able to develop effective ways to intervene and slow the process down.

What would that look like in practice? Perhaps it will be a pill that somehow influences DNA methylation and fools the body into believing time is passing more slowly than it actually is. Horvath has already done experiments that suggest this possibility. In 2013, working with skin cells in a lab, Dr. Horvath was able to reverse the biological age of adult skin cells by resetting their methylation pattern.

Will similar techniques yield anti-aging medications that reverse the signs of time on human skin? Could the effects actually be deeper than that, so that the entire body ages “slower”? One day in the future, could we extend our lifespans in a meaningful and healthy way—and what side effects could result? The science is new, and much development has yet to happen. At this point, the best anti-aging tools we have are positive lifestyle behaviours, such as regular exercise, a healthy diet, and enough sleep.

Since we are still learning about the clinical value of epigenetic testing, it is not currently available at Medcan. Should anything change, we’ll be sure to let you know.

Dr. James Aw is Medcan’s chief medical officer. Jill Furnival is a genetic counsellor at Medcan. To learn more about Medcan’s Genetics programs, contact us at genetics@medcan.com.

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