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August 12, 2016
Biological Clock Can Help Researchers Understand Aging Process

Dr. Steve Horvath
Dr. Steve Horvath

Dr. Steve Horvath believes he’s built a biological clock that’s even more accurate than the candles on a birthday cake.

The clock is an algorithm that estimates a tissue sample’s biological age by measuring DNA methylation patterns, he explained at a recent Wednesday Afternoon Lecture. DNA methylation is a natural chemical process in which compounds known as methyl groups are attached to DNA.

“The clock is a very accurate measure of tissue age,” said Horvath, professor of human genetics and biostatistics at the University of California, Los Angeles. “It’s associated with many age-related conditions, it’s a prognostic of mortality and it allows you to contrast the ages of different tissues.”

He can, for example, use the algorithm to compare heart and lung tissue samples from a middle-aged man. “I could say his heart is 50 years old and his lungs are 30 years old,” he said. Doctors might eventually be able to use this information to develop an individualized treatment plan for the patient.

To develop the clock, Horvath studied more than 8,000 samples from 82 open-source DNA methylation data sets. He identified 353 markers from 51 different types of tissue samples and looked at how DNA methylation changes during a person’s life.

The result of the clock is “literally an age estimate. And that age estimate is referred to as epigenetic age,” he said.

The clock applies to the whole life span from prenatal samples to old age. In young people, it measures “development” whereas in older people it measures “aging.”

Horvath describes his research group’s approach to aging’s “biological clock.”
Horvath describes his research group’s approach to aging’s “biological clock.”

PHOTOS: ERNIE BRANSON

The clock ticks fastest in people under 20 years old. Once a person reaches adulthood, the clock slows down to a more constant ticking rate, Horvath noted. Over time, stress factors, whether they are environmental or genetic, influence the clock. That’s why the heart of a 30-year-old can be older than other parts of the body.

There are several diseases that age brain and blood tissue faster than normal, according to the clock’s results. Down syndrome, Parkinson’s disease, HIV infection and Alzheimer’s disease are just a few examples. Horvath isn’t sure why this is the case.

He has also analyzed obesity’s effect on blood, liver and adipose tissue. He found thehigher a person’s body mass index, the higher the age of his or her liver. Blood and adipose tissue didn’t age much. “That already teaches us something,” he said. “Stress factors that age you probably will age you in a tissue-specific manner.”

He studied tissue samples from obese people who had bariatric surgery, an operation that helps patients with extreme obesity lose weight. Over the course of 9 months, most patients who have the surgery lose weight rapidly.

“The depressing news is once your liver’s age is accelerated due to obesity, an intervention will not reset the age—at least not in the short term,” he said.

Some parts of the body age slower than the rest. In a study of centenarians—those older than 100—and supercentenarians—those older than 110—he found that the cerebellum, a part of the brain that regulates motor control, is usually the youngest part of the brain.

“If we can figure out why the cerebellum stays young, maybe we [can] find a way to keep the rest of the brain young, as well,” he said.

The clock, however, isn’t perfect. Female breast tissue “almost always overestimates [chronological] age.” Breast tissue may simply be older than the rest of the body or the clock is “poorly calibrated,” which means the clock may lead to higher error. Hormone exposure might explain this, but he isn’t certain.

And, in general, Horvath said the presence of cancer can both increase and decrease the methylation-dependent age of affected tissue. “The epigenetic clock is broken in cancer tissue,” he declared.

The results from Horvath’s clock are preliminary. More research needs to be done to understand how tissue’s epigenetic age relates to the cause and effect of disease.

Insights from the clock could eventually lead to the development of anti-aging treatments. If aging’s effects can be reduced by as little as 20 percent, he said, it could save $3 trillion in major entitlement spending over the next 50 years.

“Biological aging clocks give rise to a straightforward approach for finding anti-aging interventions,” Horvath concluded.

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