![]() The correlation of telomere length with age and mortality is weak in humans and nonexistent in some other species. In 1982, researchers thought they might have found the clock’s mechanism when they isolated telomeres, DNA-protein complexes at the ends of chromosomes that shorten each time a cell divides when telomeres become critically short, cells die.īut telomeres did not pan out as an aging clock. For example, they learned in the early 1960s that cells growing in culture aren’t immortal but instead die after only 40-60 rounds of replication, which suggested that cells harbor a kind of aging clock. Time and again in past decades, biological researchers thought a clock for aging was within reach. If the clocks can usefully illuminate how to stop the aging process from triggering age-related disorders, she added, “we could prevent not just one disease but many.” Seeing a Signal “I now have collaborators that work a lot in breast cancer and starting to think about, ‘If you have advanced biological aging, is that also informative for breast cancer?’” said Sara Hägg, a molecular epidemiologist at the Karolinska Institute in Stockholm, Sweden. ![]() Now the clocks are leading some scientists to rethink their ideas about what aging is, as well as its connection to diseases. “Epigenetic clocks are closer to the actual process of aging than any other biomarkers,” said Vadim Gladyshev, a biochemist at Brigham and Women’s Hospital and Harvard Medical School who studies cancer and aging. Scientists began using Horvath clocks in their research to measure the aging of cells because the clocks were better arbiters of the state of the body and the risk of disease than chronological age. Yet the accuracy of the clocks stood up to tests and sent ripples through the biomedical community. Many biologists were skeptical at first because the clocks were rooted in statistics rather than an understanding of biomolecular mechanisms. A dozen years ago, Horvath and his colleagues began applying their know-how to building the clocks, first to assess the age of DNA from saliva, and later to determine the age of blood, liver and other individual tissues. They are products of epigenetics (literally, “above genetics”), the field that studies heritable information not written in the genetic code. His clocks are based on analyses of the chemical tags called methyl groups that hang on DNA like charms on a bracelet and help control gene activity. Understanding why clocks like this one work, Horvath believes, could help lead us to what he calls “the true root cause of aging.” Now he and other researchers are hoping to identify the molecular processes common to diverse creatures that make such a clock possible. Horvath and his colleagues completed a version of the pan-mammalian clock earlier this year. “You want to have a biomarker that accurately measures ages in many different tissues and cell types,” said Horvath, who left UCLA this year to become a principal investigator at Altos Labs, a biotechnology startup working toward the rejuvenation of cells. For decades, scientists have searched for an objective and versatile way to measure biological aging, the changes in healthy function over time. But chronological age is an imperfect metric since some individuals and tissues show the effects of age more rapidly than others. Measuring age might seem to be no harder than using the nearest clock or calendar. But those were merely steps toward the completion of Horvath’s ambitious moonshot of a project: a universal clock that could measure the biological age of any mammal. ![]() With that vast menagerie of samples, he has built computational clocks that can calculate the age of creatures as diverse as shrews, koalas, zebras, pigs and “every whale you can name,” he said, just by looking at their DNA. He has reached out to the far corners of the world, begging for the DNA of flying foxes, vervet monkeys, minipigs and bowhead whales. He has attended talks on bats and Tasmanian devils to meet their keepers. ![]() Since the summer of 2017, Horvath, who until recently was an anti-aging researcher at the University of California, Los Angeles, has spent as much as 10 hours a day penning emails to zoos, museums, aquariums and laboratories. “I didn’t have any of that order, which is why I desperately wanted them,” he recalled. The ancient scaly anteater would be a first for his collection, which was then about 200 mammals strong. This time a year ago, Steve Horvath was looking for pangolin DNA.
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