How the Epigenetic Clock Can Predict Age

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A couple of weeks ago, before we got seriously distracted by COVID-19, I wrote about new research that scientists in Europe, the United States, and beyond have done to pin down the exact mechanisms associated with aging.

As I describe in Exercise Is Medicine, that there are nine major “hallmarks” of aging; that is, nine specific genetic and molecular events that comprise the process of aging. The good news is that exercise can affect all nine of these in a positive direction. The bad news is that eating too much and exercising too little has the opposite effect.

One of the most intriguing of these hallmarks is the epigenetic clock. This is a kind of biological metronome that “is literally an age estimate for any cell type, tissue type or organ,” says Steve Horvath, a professor of human genetics and biostatistics at the University of California, Los Angeles.

Epigenetics, in case you’ve forgotten, consists of the changes to DNA that influence which genes are active but don’t change the DNA itself. (Changes to the DNA itself are called mutations.) The epigenetic clock is actually just one of a number of biological clocks that help the body keep track of time. When should we get hungry? When should we sleep? When should we conceive babies? The most familiar of these clocks is the circadian clock, which keeps track of day and night.

But the epigenetic clock stands out because of its surprisingly strong relationship with chronological age. As Horvath puts it, it’s like counting the rings on a tree to estimate its age.

Here’s where it gets even more interesting. One of the chief epigenetic changes is a process called DNA methylation. That sounds intimidating, but it’s really not. DNA methylation is the process that happens when a chemical structure called a methyl group latches on to certain stretches of DNA. Depending on where the methyl group lands, it can control the expression of particular genes. As we age, some sites on DNA gain methyl groups and others lose them.

The coolest study I came across while researching is this one: In 2014, Swedish researchers asked a group of healthy young men and women to subject themselves to muscle biopsy tests in both legs, then asked them to ride bikes in the lab using only one leg four times a week for 45 minutes for three months. Then the muscle biopsies were repeated.

The scientists found that more than 5,000 sites on the genome of muscle cells had new methylation patterns, with some sites showing more methylation and some, less. The fascinating thing was that these changes only showed up in the exercised leg, not the control leg. It was a perfect experiment, same person, same diet, same sleep patterns, everything. Except that one leg got exercise and the other didn’t. Bottom line? The exercised leg appeared to show a slowing of the epigenetic clock.

Scientists who study the epigenetics of aging have made some other intriguing discoveries, too. As anybody can tell at a high school or college reunion, we don’t all age at the same rate. Despite having the same chronological age, in other words, we vary widely in the rate at which we age at the basic molecular level.

Indeed, some ethnic groups seem to age faster than others, according to epigenetic research. Men age faster than women. Even different tissues in the same body age at different rates. The heart, for instance, can be 50 years old, according to the epigenetic clock, and the lungs, 30.

DNA methylation can actually predict all-cause mortality, regardless of chronological age. In one 2016 study of 13,000 people, for instance, Horvath’s team showed that the epigenetic clock was able to predict the life spans of Caucasians, Hispanics, and African-Americans “even after adjusting for traditional risk factors such as chronological age, gender, smoking, body-mass index, disease history, and blood cell counts.”

Some data even suggest that there is a 35 percent increase in the risk of death for each 5-year increase in DNA methylation age.

Pretty sobering stuff, isn’t it? Makes you want to jump on one of those exercise bikes and pump away. With both legs, of course.