These companies are like 23andMe, but instead of purporting to reveal your ancestral past, they claim to divine, and allow you to intervene in, your biological future. Online, a half-dozen or more companies sprang up selling versions of Horvath’s clocks for around $200, promising prophetic insights to largely affluent customers concerned with prolonging their youth. Scientists started to investigate whether the algorithms could be used to help solve crimes by using genetic material left at crime scenes-blood, hair, skin cells, bodily fluids-to determine the age of unknown victims or perpetrators. Almost as soon as Horvath began publishing the research on his clocks, people began to realize their potential to shape domains from law enforcement to healthcare. This was a scientific breakthrough with an uncommonly wide range of applications, some of them quite unsettling. Horvath and his colleagues called this new epigenetic clock GrimAge, after the grim reaper, because it seemed to have the disturbing potential to tell if you were headed for a premature death. It turned out that the 5 percent of people with the highest epigenetic age relative to their chronological age were twice as likely to die prematurely as an average person of their chronological age. With a group of fellow researchers, he set out to develop a new algorithm that would analyze methylation patterns at DNA sites associated with mortality and compare them to the age of death of subjects in large longitudinal studies. He hypothesized that people with a higher epigenetic age than chronological age (the one we mark with birthdays and greeting cards) might be at a higher risk of early death. Horvath referred to his successful algorithm as an “epigenetic clock”: insert some body tissue, and it would spit out your epigenetic age. After Horvath finally convinced a journal to publish his results, other researchers began to replicate them. The pattern of methylation at just 353 of the three billion or so pairs of DNA nucleotides in the human genome corresponded to a person’s age with 96 percent accuracy, an unprecedented degree of correlation between a biomarker and the process of aging. What he found was so remarkable that several academic journals rejected his results out of hand. Then he tested the algorithm on the other half of the datasets. Horvath used about half of these datasets to train an algorithm to look for associations between DNA methylation and age. The data came from a wide range of people of different ages, and from different parts of the body: cord blood from newborns in various parts of the world brain, stomach, lung, liver, breast, and uterine tissue sperm immortalized B cells from people with a rare genetic disease. By 2012, he had gathered eighty-two datasets with eight thousand samples in them. To find out how robust this relationship was, Horvath began gathering publicly available datasets that included information about subjects’ age and DNA methylation patterns. DNA methylation predicted age to within five years in more than 85 percent of the subjects. The sample was small, but the correlation was strong. In 2011, Horvath measured methylation in DNA from saliva samples and found that the more cells a person had with a particular methylation pattern at three DNA sites, the older a person tended to be. One was a process called DNA methylation, in which small molecules of carbon and hydrogen attach to particular parts of a person’s genetic code, with the ability to activate or suppress the underlying genes. Horvath began looking for epigenetic processes that might correlate with aging in humans. Some serve as foragers, others as soldiers, living about a year and never reproducing only one ant rules as queen, laying eggs and living for up to thirty years. All the females in a floridanus colony share the exact same set of genes, but their behaviors and lifespans are dramatically different. To illustrate the power of epigenetics, some scientists point to the differences among females in the colonies of certain ant species, including Camponotus floridanus, the Florida carpenter ant. If you imagine DNA as a ribbon of patterned cloth, epigenetic processes can be thought of as a sort of embroidery that accentuates or conceals its design. He was working in a relatively new field called epigenetics, the study of how biological processes alter gene expression without changing our underlying DNA. Horvath began his work on that question in the mid-2000s, as a professor at the University of California, Los Angeles. After getting degrees in mathematics and biology, he started building statistical models hoping to answer an intimate, terrifying question: how long do we each have to live before we die? The geneticist Steve Horvath likes to recall a pact he made with his identical twin at the end of high school in the late 1980s-they would dedicate their careers to extending the human lifespan.
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