How biological clocks predict life span

Age is much greater than the number of birthdays one had. Stress, sleep or diet, for example, have a huge impact on how our organs wear down. The influence of these factors can cause us to age faster or slower than people born on the same day. This means that our biological age can be very different from our chronological age.

Researchers suggest that biological age better reflects physical health and even mortality than chronological age. But the calculation is not so simple. In the past 10 years, scientists have developed so-called biological clocks, also known as aging clocks, which use biomarkers in the body to determine our biological age.

The big idea behind these biological clocks is that they can basically show how much our organs are breaking down. Thus they predict how many healthy years a person will still have. However, among the hundreds of clock aging methods that have been developed over the past decade, there is great variation in accuracy. And researchers are still grappling with an important question: What does it mean to be biologically young?

Most biological clocks estimate a person’s biological age based on patterns of epigenetic marks called methyl groups, which within DNA influence gene expression. The pattern of this methylation at thousands of sites in DNA appears to change with age, although the reason for this is not clear.

Some biological clocks promise age prediction by estimating how old a person’s body is, while others work like a speedometer, to keep track of the pace of aging. Aging clocks have been developed for specific organs of the body and for different animal species.

Proponents of this technology are already trying to use it to show that anti-aging can biologically make people younger. But there are also criticisms: there is not enough knowledge 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 looked for epigenetic markers in saliva samples that could explain sexual orientation. (Steve Straight, Marcus Gay).

As a biostatistician, Horvath offered to analyze the results – ultimately finding no connection to sexual orientation. But at the same time he was also looking for links between people’s age and epigenetic markers. “I fell off a chair because the signal of the aging process was strong,” he says.

He found that methylation patterns can predict a person’s age in years – although estimates differ for the chronological ages of individuals by an average of about five years.

Since then, Horvath has been working on biological clocks. In 2013 he developed the Horvath watch named after him, still one of the most popular aging watches today which he calls a “cross-tissue” watch because it can estimate the lifespan of nearly every organ in the body. Horvath built his system using methylation data from 8,000 samples taken from 51 body tissue and cell types. Using this data, he trained an algorithm that could predict a person’s chronological age based on a sample of cells. Other groups have developed similar technologies, of which today there are hundreds. However, Horvath estimates that fewer than 10 of them are used in human studies — primarily to assess how diet, lifestyle or supplements affect aging.

So what can all these old clocks tell us? It depends. Most biological clocks are designed to predict the chronological age of a sample. But Morgan Levine of Yale University School of Medicine in New Haven, Connecticut, points out, “That’s not the point. We can just ask someone their age.” In 2018, Levine, Horvath and their colleagues developed a biological clock based on nine biomarkers — including blood glucose and white blood cell levels, as well as a person’s age in years.

They then used the data collected as part of another study of thousands of people in the United States who were followed over the years. The resulting circadian clock, dubbed “DNAm PhenoAge,” says Levine, estimates biological age better than other systems that rely solely on chronological age.

A one-year increase in “apparent” lifespan is associated with a 9 percent increased risk of death, regardless of cause, according to the watch — as well as an increased risk of dying from cancer, diabetes or heart disease. If your biological age is higher than your chronological age, you are expected to age faster than average, says Levine. But that’s not necessarily the case, comments Danielle Belsky of Columbia University’s Mailman School of Public Health in New York City. According to him, there are many reasons why the biological age exceeds a person’s years.

Belsky and colleagues have developed a tool to more accurately measure the rate of biological aging. To do this, they tracked the health of 954 volunteers in four age groups 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 overall health. Then they developed a genetic “speedometer” to predict how these values ​​would change over time.

Another common biological clock was developed by Horvath and colleagues called the GrimAge, in reference to the Grim Reaper. Horvath claims to offer the best quality of predicting mortality to date. He applied it to his blood samples. He said his results matched his chronological age two years ago, but when he took another test about six months ago, his GrimAge was four years older than his age in years. This does not mean that Horvath should subtract four years from his age. “You can’t relate it directly to life expectancy,” he says. But he thinks the result means he’s aging faster than he should be – although he’s still at a loss as to why.

Other people have found through changes in their results that the aging process slows down, usually after they start taking a supplement. However, in many cases, the change can be explained by the fact that many epigenetic aging clocks are subject to noise—and are prone to random errors that skew their results.

The problem is that wherever in the body the methyl groups are attached to the DNA, little changes over time. These subtle changes can be amplified by errors. This is a big problem, says Levine. Results can vary by decades.

To solve this problem, they “disassemble” and compare existing old clocks. They hope to find out what the different systems actually measure – and how better methods can be developed in the future. Levin and colleagues worked to eliminate interfering signals and background noise. The team also wants to understand what the old clocks are telling us. What does it really mean to have a lower biological age? How can this knowledge be applied in practice?

While the aging of hours can be a good indicator of overall health, in most cases it is not accurate enough to rely on for risk assessment. “I think they haven’t reached their full potential yet,” says Levine.

This potential could lie in clinical health testing, Horvath says, where aging clocks can be used in conjunction with blood pressure and cholesterol measurements in the future to help people understand their fitness and health, or whether they are more likely to develop disease. “Epigenetic clocks will never replace clinical signs, but clocks can supplement them,” he says. “I think five years from now we will have blood-based systems that are very valuable. [klinisch] It can be used.”

In the meantime, a healthy diet, smoking cessation and adequate exercise remain the best ways to stave off the effects of aging. It doesn’t take hours to get old to show that these strategies can help keep us healthy.



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