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Matter of Time

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“Biological age is what is important. If we can learn what accelerates the aging process and also what helps to keep people biologically young, we might be able to delay the onset of many age-related conditions.”

ALL OVER THE WORLD, PEOPLE ARE LIVING LONGER. Life expectancy at birth is now 80 or older in 33 countries (it is 79 in the United States). Today, one of every nine people is over 60; by 2050, one in five will be.

But Dr. Steve Horvath, professor in the Fielding School’s Department of Biostatistics, points out that as the life span continues to rise, the “health span” isn’t keeping pace. “Advances in medical treatment often keep people alive longer without preventing or reversing the decline in overall health,” Horvath explains. “As a result we have more older people plagued by chronic diseases, which leads to more disabilities and massive health care costs.”

Horvath notes that age is arguably the most important determinant of chronic disease risk. But he and other researchers who study aging draw a distinction between chronological and biological age. “Biological age is what is important,” says Horvath, who in addition to his Fielding School appointment is a professor in the Department of Human Genetics at the David Geffen School of Medicine at UCLA. “If we can learn what accelerates the aging process and also what helps to keep people biologically young, we might be able to delay the onset of many age-related conditions.”

Finding reliable biological measures of aging has been a longstanding research priority, based on the premise that these so-called biomarkers would lead to a better understanding of how aging increases susceptibility to certain diseases, along with identifying strategies for promoting healthy aging. In recent years, fueled by breakthrough technologies that allow researchers to analyze genetic patterns with unprecedented speed and precision, a once elusive pursuit has come into focus.

In 2013, Horvath made a seminal contribution to the effort in the scientific journal Genome Biology with the publication of what is now a widely used method for estimating and comparing biological ages of different parts of the human body. His “epigenetic clock” is a culmination of more than three years of collecting and analyzing publicly available data on more than 13,000 tissue samples from laboratories around the world. The clock has been likened to determining the age of a tree by counting its rings. Although Horvath is quick to state that the tree analogy is hyperbole, his method was hailed by the prominent international journal Nature, which featured Horvath under the headline “The Clock Watcher” and wrote that the epigenetic clock “has impressed researchers with its accuracy, how easy it is to read and the fact that it ticks at the same rate in many parts of the body – with some intriguing exceptions that might provide clues to the nature of aging and its maladies.”

Horvath believes the epigenetic clock, available to other researchers through free software, is helping to usher in a new frontier for aging research. Among other things, studies using the biomarkers may help to distinguish which diseases are related to cellular aging as opposed to toxic exposures or other factors – for example, smoking does not appear to affect biological aging, despite all of its other harmful effects. A better understanding of aging-related diseases, Horvath says, might lead to more targeted lifestyle strategies to delay the onset of cognitive and physical decline, and potentially even therapeutics designed to slow the biological aging process, much like statin drugs control cholesterol levels.

The clock estimates the biological age of human tissues, cells, and organs through epigenetic changes – chemical modifications to the genome that can influence the way genes are expressed. Using several hundred epigenetic markers in the human genome, Horvath and his colleagues showed that the epigenetic clock pinpoints with unparalleled accuracy the age of nearly every tissue or cell type that contains DNA, across the entire age spectrum. Subsequent studies have found that the epigenetic clock can be used to predict life span.

“There is no debate that epigenetic changes play a critical role in development, but our findings provide compelling evidence that these changes play a similarly important role in aging and make people more susceptible to a host of chronic diseases, as well as cognitive decline,” Horvath says. “As a trained biostatistician, I looked at the genomic data without any biases, and these epigenetic biomarkers dwarfed any other data.”

Now the question for Horvath and other researchers is whether interventions that slow down the epigenetic clock also slow the biological aging process. “We have seen associations between a faster-running epigenetic clock in late life and poorer physical and cognitive health, in addition to a shorter life span,” says Dr. Riccardo Marioni, an epidemiologist at the University of Edinburgh in Scotland. Marioni is collaborating with research teams around the world, including Horvath’s, on studies seeking to understand what factors cause the epigenetic clock to run faster – and to see if the clock can be “wound back” via lifestyle changes. “This research could help inform older individuals about lifestyle choices to maximize healthy aging,” Marioni says.

Concludes Horvath: “It is a demographic certainty that our society will face catastrophic health care costs unless we rise to the challenge of delaying disabilities and the onset of chronic diseases. If we could extend the health span by a mere five years, we could prevent a tsunami of suffering and economic hardship due to health care costs, disability costs, and retirement costs. I think of the epigenetic clock as night vision goggles in our fight against aging. It allows us to measure how fast tissues and organs age. What we can measure, we can study – and ultimately defeat.”