Aging clocks aim to predict how long you will live

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Most aging clocks estimate a person’s biological age based on patterns of epigenetic markers, specifically chemical tags called methyl groups that are layered on DNA and affect how genes are expressed. The pattern of this methylation at thousands of sites in DNA appears to change as we age, although it’s not clear why.

Some clocks promise to predict life expectancy by predicting how a person’s body ages, while others act more like a speedometer, tracking the rate of aging. Clocks have been developed for specific organs of the body and for many animal species.

Advocates of aging clocks are already trying to use them to show that anti-aging interventions can make individuals biologically younger. However, we do not yet know enough to make such claims about the watches or what they tell us.

monitoring time

The first epigenetic clock for aging was developed in 2011 when Steve Horvath of the University of California, Los Angeles volunteered to participate in a study with his identical twin Markus. The study looked for epigenetic markers that could explain sexual orientation in saliva samples. (Steve is straight and Markus is gay.)

As a biostatistician, Horvath offered to analyze the results and found no link with sexual orientation. But he also looked for links between the volunteers’ age and epigenetic markers. “I fell out of my chair because the signal was too big to age,” he says.

He found the methylation patterns. can predict a person’s age although estimates differ by an average of five years from each person’s chronological age.

Horvath has been working on obsolete watches ever since. self-titled in 2013 hour, still among the most well-known aging clocks today, he calls it the “pan-tissue” clock because it can predict the age of almost every organ in the body. Horvath created the clock using methylation data from 8,000 samples representing 51 body tissues and cell types. With this data, he trained an algorithm to estimate a person’s chronological age from a sample of cells.

Other groups have developed similar watches, and today there are hundreds of them. But Horvath estimates that less than 10 are commonly used in human studies, primarily to assess how diet, lifestyle or supplements may affect aging.

age measurement

What can all these hours tell us? It varies. Most watches are designed to estimate chronological age. But Morgan Levine, of the Yale School of Medicine in New Haven, Connecticut, says: “To me, that’s not the point. We can ask someone how old he is.”

In 2018, Levine, Horvath and colleagues developed a clock based on nine biomarkers, including a person’s age, as well as blood glucose and white blood cell levels.

They used data collected from thousands of people in the United States as part of a different study that followed the participants for years. Levine says the resulting clock, called DNAm FenoAge, is better at predicting biological age than clocks based solely on chronological age.

One-year increase in age, which Levine calls the “phenotypic” age, by the hourare associated with a 9% increase in death 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, Levine says.

But that may not be the case, says Daniel Belsky of Columbia University’s Postman School of Public Health in New York. He says there are many reasons why biological age may exceed a person’s years.

Belsky and colleagues developed a tool to more accurately measure the rate of biological agingBased on a study that followed the health outcomes of 954 volunteers aged four years between their mid-20s and mid-40s. Researchers looked at biomarkers believed to indicate how well various organs were working and others linked to overall health. They then developed an epigenetic “accelerometer” to predict how these values ​​would change over time.

Another popular watch, also developed by Horvath and his colleagues, is called the GrimAge and pays homage to the Grim Reaper. Horvath claims to be the best at predicting mortality and applies it to his own blood samples.

He says his results are consistent with his chronological age two years ago, but says his GrimAge was four years older than his age when he took another test about six months ago. That doesn’t mean Horvath shortened his life by four years – “You can’t directly relate to how long you’ll live,” he says – but he thinks that means he’s aging faster than he should, but he’s still confused. by reason.

noisy hours

Others used the changes in their results to infer that aging rates slowed down, usually after they started taking the supplement. In many cases, however, the change can be explained by the fact that many epigenetic aging clocks are “noisy” and prone to random errors that skew their results.

The problem is that little changes occur over time in every part of the body where methyl groups attach to DNA. These subtle changes can be magnified by errors in methylation estimates. Levine says this is becoming a big problem, and the consequences could disappear after decades.

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