Most clocks of aging estimate a person’s biological age based on patterns of epigenetic marks — specifically, chemical marks called methyl groups that are layered on DNA and affect how genes are expressed. The pattern of this methylation across thousands of sites on DNA appears to change as we age, although the reason is not clear.
Some watches promise life expectancy by estimating how old a person’s body is, while others work like a speedometer, tracking the pace of aging. Clocks have been developed for specific organs of the body and for multiple animal species.
Proponents of antique clocks are already trying to use them to show that anti-aging interventions can make individuals biologically younger. But we don’t yet know enough about the watches, or what they tell us, to make such claims.
The first epigenetic aging clock was developed in 2011 when Steve Horvath of the University of California, Los Angeles, volunteered to participate in a study with his identical twin brother Marcus. The study was looking for epigenetic markers in saliva samples that might explain sexual orientation. (Steve is straight and Marcus is gay).
As a biostatistician, Horvath offered to analyze the results and find no link to sexual orientation. But he also looked for links between the volunteers’ age and epigenetic markers. “I fell off a chair, because the sign was huge for aging,” he says.
He found that methylation patterns could predict a person’s age in years, although estimates differed on average by about five years from each person’s chronological age.
Horvath has worked on obsolete watches ever since. In 2013, he developed the eponymous Horvath clock, still among the most popular aging clocks known today, which he calls the “Pan Tissue” clock because it can estimate the lifespan of nearly any organ in the body. Horvath built the clock using methylation data from 8,000 samples representing 51 body tissue and cell types. Using this data, he trained an algorithm to predict a person’s chronological age from a cell sample.
Other groups have developed similar watches, and there are hundreds of them today. But Horvath estimates that fewer than 10 are widely used in human studies, primarily to assess how diet, lifestyle, or supplements affect aging.
What can all these hours tell us? It depends. Most watches are designed to predict chronological age. But Morgan Levine at Yale University School of Medicine in New Haven, Connecticut, says, “For me, that’s not the point. We can ask someone their age.”
In 2018, Levine, Horvath and their colleagues developed a clock based on nine biomarkers, including blood glucose and white blood cell levels, as well as a person’s age in years.
They used data collected from thousands of people in the United States as part of a different study that followed participants for years. The resulting clock, called the DNAm PhenoAge, is better at estimating biological age than clocks that rely solely on chronological age, Levine says.
A one-year increase in what Levine calls “apparent” age, according to the clock, is associated with a 9% increase in deaths from any cause, as well as an increased risk of dying from cancer, diabetes or heart disease. If your biological age is higher than your chronological age, it’s fair to assume that you’re aging faster than average, says Levine.
That may not be the case, says Daniel Belsky of Columbia University’s Mailman School of Public Health in New York City. He says there are many reasons why a person’s biological age may exceed a person’s years.
Belsky and colleagues developed a tool to more accurately measure the rate of biological aging, based on work that tracked the health outcomes of 954 four-year-old volunteers between their mid-20s and mid-40s. The researchers looked at biomarkers thought to indicate how well different organs were working, as well as other indicators associated with general health. Then they developed a genetic ‘speedometer’ to predict how these values would change over time.
Another popular watch, developed by Horvath and his colleagues, is called the GrimAge, in reference to the Grim Reaper. Horvath claims to be the best at predicting mortality, and he applied it to his blood samples.
His results were consistent with his chronological age two years ago, he said, but when he took another test about six months ago, the GrimAge was four years older than his age in years. That doesn’t mean Horvath has shaved off four years of his life — “you can’t directly link it to how long you’re going to live,” he says — but he thinks it does mean he’s aging faster than he should, although he’s still at a loss as to why.
Others used changes in their results to conclude that their rate of aging slowed, usually after they started taking a supplement. But in many cases, the change can be explained by the fact that many clocks of epigenetic aging are “noisy” – prone to random errors that distort their results.
The problem is that in every area of the body where methyl groups attach to DNA, very small changes occur over time. These subtle changes can be amplified by errors in methylation estimates. It ends up becoming a huge problem, and the results can be decades away, Levine says.
Aging clocks aim to predict how long you will live
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