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Saturday, June 22, 2024

How Old Are You, Really? New Tests Want to Tell You

Age is just a number—and one you may be able to change. At least that’s the pitch behind Tally Health, a new startup that’s among a crop of companies selling tests that offer to tell consumers their “biological age.”

You’ve heard of at-home tests like those from 23andMe and Ancestry, which scan your DNA to provide information about ethnic heritage and health risks. Now, a wave of startups is marketing tests that claim to parse your blood, urine, or a cheek swab to reveal your biological age. The tests measure epigenetic patterns, or changes in the body that affect how genes behave. Unlike a calendar age, which marches along at the same pace for everyone, biological age is the speed at which cells, tissues, and organs appear to decline—and that can vary, depending on a person’s health history.

Tally Health, which launched last week, is one of around a dozen companies that offer these tests. Harvard University biologist David Sinclair, the company’s cofounder, describes its version as something like a credit score for your body. You swab your cheek, drop your sample in the mail, and the company sends you back your biological age. “If you're younger, that's great. We want to keep you there and even make you stay younger as you get chronologically older,” Sinclair says. “If you come up with a number that's older than your cohort, then we’re here to help get you back to not just average, but even below average, biological age.”   

Genetics and lifestyle both contribute to aging. Choices like diet, exercise, smoking, and drinking alcohol all cause epigenetic changes in how genes behave. Exposure to stress, trauma, and pollution can also have an effect. Scientists think the accumulation of all these factors affects a person’s biological age, but Sinclair believes that genetics are far less important than factors that are largely within a person’s control. (Sinclair is 53, but he says that, according to Tally Health’s test, his biological age is more like 43.)

Sinclair is an influential and often controversial researcher in the antiaging field thanks to his promotion of resveratrol, a compound found in red grapes, which he once called “as close to a miraculous molecule as you can find.” Other researchers have been more cautious about resveratrol’s possible benefits, given its mixed results in animal tests. (Sinclair takes resveratrol supplements daily, and his Harvard lab is still pursuing research on the compound). Sinclair has founded several biotech companies, including ones focused on longevity, and his 2019 book Lifespan: Why We Age–and Why We Don’t Have To, debuted on The New York Times bestseller list. 

“What we are trying to do, at the highest level, is to change the way we age,” says Melanie Goldey, CEO of Tally Health. “It's one number that tells you how your body is really aging versus how many birthdays you've had.” (Goldey says her biological age is about six months younger than her chronological one.)

In addition to giving each customer an age reading, the New York City–based company provides an action plan of personalized lifestyle recommendations, such as getting more sleep, spending less time sitting, minimizing stress, or eating more vegetables—arguably things that most people could benefit from. Users can take a one-time test for $229 or get a membership to test every three months so they can monitor their biological age over time. “We think that's a good amount of time for people to get their action plan, be empowered by the information, choose the adjustments they want to make, and actually implement some change,” Goldey says.  She says the company had amassed a wait list of more than 270,000 people when it launched, although she didn’t say how many people have signed up for a membership, which ranges from $129 to $199 a month.

Like other epigenetic aging tests on the market, Tally Health looks at patterns in DNA methylation—the chemical tags on DNA code that affect the activity of genes. In the 1970s, scientists made the connection between DNA methylation and aging. In 2013, Steven Horvath, a geneticist and biostatistician at UCLA, published the first epigenetic aging “clock” based on these changes. The clock is a predictive test based on data from 8,000 biological samples of 51 healthy human tissues and cell types. It measures DNA methylation patterns associated with aging and disease and uses an algorithm to guess a person’s age. 

The next wave of epigenetic clocks sought to go a step further to predict how long a person was going to live—or how many of those years would be healthy ones. One of those was PhenoAge, a clock published by Morgan Levine at Yale University in 2018. Based on a person’s blood sample, it predicted overall mortality risk and the risk of cancer, cardiovascular disease, and Alzheimer’s, among other outcomes. A year later, a team led by Horvath and Ake Lu released GrimAge, an improved version of their earlier clock that predicts a person’s time until death based on a blood sample. 

These clocks were meant to be used by researchers to test the antiaging effects of drugs or lifestyle changes in animals or people. Indeed, studies have shown that people who test as biologically older than their chronological age are at increased risk of certain diseases and death. But companies have since sprung up to make clocks of their own or adapt existing ones into direct-to-consumer tests. 

The technology behind Tally Health’s test was developed in Sinclair’s lab at Havard and was described in a preprint paper posted last year. Using cells from a cheek swab, the company estimates biological age by measuring how a person’s DNA methylation patterns compare to samples the company took from 8,000 people ranging from 18 to 100 years old, according to Goldey. About half the samples came from men and the other half from women, while 30 percent were from non-white individuals. 

There are several others on the market: Since 2017, Zymo Research, based in Irvine, California, has offered a $299 blood or urine test called myDNAge that’s based on Horvath’s biological aging clock. The company provides a personalized report that includes information on a customer’s metabolic health, methylation activity, and potential risk for age-related diseases. And in 2019, supplement-maker Elysium Health of New York City launched a $299 biological aging test that it developed in partnership with Levine, who was recruited last year by Altos Lab, a $3 billion life-extension company in San Diego.

“We think that some people age more slowly and live long, healthy lives, while others age more rapidly and have early onset of chronic diseases,” says Daniel Belsky, an associate professor of epidemiology at Columbia University who focuses on aging. “Biological age is a way of trying to summarize those differences between people.”

What’s unknown, Belsky says, is whether current epigenetic tests are sensitive enough to pick up on lifestyle changes that people may make over a relatively short period of time. Even if they are, no one has repeatedly tested enough people to know whether their scores track with changes in their overall health and longevity. “We don't have a great deal of knowledge yet about how well these serve as monitors of an individual’s aging progress,” Belsky says.

In a recent study, Belsky and his Columbia colleagues wanted to see if a reduced-calorie diet had antiaging effects on people. Healthy adults in a two-year clinical trial were separated into two groups—one that ate a normal diet and another that ate a 25 percent-calorie-restricted diet. The researchers analyzed participants’ blood samples taken at the start of the trial, one year in, and at the end of the trial using three measures: PhenoAge, GrimAge, and a clock developed by Belsky and his collaborators called DunedinPACE, which estimates a person’s pace of aging.

The PhenoAge and GrimAge clocks found that the calorie-restricted diet had no meaningful effect on a person’s biological age. But DunedinPACE showed that it did slow the pace of aging. “In other words, some of these tools may not be optimized for detecting small changes in biological age,” Belsky says. (TruDiagnostic, a company out of Kentucky, sells DunedinPACE as a consumer test.) 

Charles Dupras, a bioethicist at the University of Montreal, who has studied direct-to-consumer epigenetic testing, says people may benefit from such tests because they serve as inspiration for healthier habits. “Just having this tool may serve as a positive source of motivation for people,” he says. But he says companies need to be careful that they’re not making exaggerated claims about the potential benefits of their tests. Plus, these tests just haven’t been around long enough to know whether they actually lead people to make healthier decisions.

Eric Verdin, president and CEO of the Buck Institute for Research on Aging in Novato, California, is excited about the potential for biological aging tests—and his institute is one of several groups developing them. “They are great research tools,” he says. “But this is still early days for these tests. In my opinion, they’re not ready for prime time.” For one thing, he says, it’s not clear if all of the tests on the market have been validated by other scientists. Verdin also cautions that these tests haven’t been evaluated by the US Food and Drug Administration and aren’t regulated. 

Sinclair doesn’t see a downside to knowing your biological age. “By having a number, it’s like having a dashboard on your body,” he says. “We think it gives you the empowerment, the determination to make a change in your life.” 

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