Susannah Woodruff can’t wait to stop pulling teeth out of polar bears.
Dr. Woodruff, a wildlife biologist with the US Fish and Wildlife Service, monitors the bear population in Alaska. He needs to know how old they are to estimate how many will soon die of old age, and how many will enter their reproductive years and start giving birth.
Until recently, the only reliable way to determine a polar bear’s age was to extract a premolar and examine its growth rings. “No researcher wants to do this,” said Dr. Woodruff in an interview Monday, before embarking on a trip to Alaska’s North Slope.
On this trip, instead of pulling teeth, he’ll just draw blood. Using a method known as the epigenetic clock, he and his colleagues were able to estimate the age of the bears by analyzing chemical tags in their DNA. He and his colleagues recently found that using this method provides an estimate to within a year of the bears’ true age, making it more accurate than examining teeth.
The clock’s implications go beyond polar bears. On Thursday, an international team of scientists published a study in the journal Nature Aging showing that epigenetic clocks tick in 185 different mammal species, including humans. That study, as well as a related one published Thursday in the journal Science, suggest that the epigenetic clock starts ticking shortly after an organism’s fertilization, and that its speed determines how long a species will live.
“You have a bat, you have a whale — which has a completely different ecology — but you can use the same mathematical formula to measure aging,” said Steve Horvath, who led both new studies as principal investigator at Altos. Labs, a biotech company based in the San Francisco Bay Area. “It was absolutely stunning.”
The epigenetic clock is made possible by millions of tiny molecules called methyl groups strung into our DNA like Christmas lights on a wire. When a cell divides, the DNA in the two new cells usually ends up with the same, unique pattern of methyl groups. But our cells also have enzymes that can cleave methyl groups in DNA.
Scientists have known about methylation for decades, but they’re still trying to figure out exactly what its purpose is. It probably has something to do with keeping genes active or silent. Adding methyl groups around a gene can be a step in shutting it off, while removing them can involve turning the gene back on.
In the 1960s, Soviet scientists noticed that as salmon aged, their DNA became less methylated. In recent years, some studies have found a similar pattern in other species. And other research has found that certain regions of DNA gain extra methyl groups with age.
In the early 2010s, Dr. Horvath, then at the University of California, Los Angeles, wondered if he could predict an organism’s age from its methylation pattern alone. He fed a computer methylation data from thousands of human cells. Then trained by Dr. Horvath machined that data to predict the age of people the cells came from.
Dr. Horvath reported in 2013 that a computer needed to analyze only 353 spots in a cell’s DNA to make a prediction to within a few years of a person’s chronological age. In the decade since, he and others have tried to develop more precise epigenetic clocks. Research has shown, for example, that smoking, obesity and drinking can add years to the epigenetic clock, and that this acceleration in biological age predicts a greater risk of death.
However, there is much about epigenetic clocks that scientists do not yet understand. “We know it works, but we don’t know why,” said Alexander de Mendoza, a molecular biologist at Queen Mary University of London.
That uncertainty has left some skeptics wondering if the epigenetic clock reveals anything that might make a medical difference. “I’m still waiting to be convinced that the metric that’s been developed has any value,” said Dr. John Greally, an epigenetics expert at the Albert Einstein College of Medicine in New York.
Dr. Horvath and his colleagues responded to the skeptics by seeking a deeper molecular understanding of the clock. In the new project, Dr. Horvath to biologists who study mammals and asked for blood and tissues to analyze. They sent him materials from hundreds of species.
Scientists have trained a computer to create a new clock that can predict the age of animals based on a single epigenetic pattern across species. It made good predictions about the age of 185 species by looking at fewer than 1,000 spots in mammal DNA.
This finding means that biologists can estimate the age of animals more easily than in the past – not just polar bears, but any wild mammal. As the technology develops, researchers hope to move from blood to saliva or perhaps feces, which can be collected in less invasive ways.
“This is a major breakthrough in the field and a fascinating and important discovery,” said João Pedro de Magalhães, an aging expert at the University of Birmingham who was not involved in the study. Dr. predicted de Magalhães that this will not only help biologists more accurately estimate the age of wild animals, but also help understand why all mammals – including us – age.
The first results from epigenetic clocks also created a new market. Several companies now offer to estimate people’s biological age by measuring their epigenetic clock. But none of those tests have been approved by the Food and Drug Administration.
“There are a lot of shenanigans and snake-oil sellers who have tried to make money here, and the epigenetic clock field is certainly prevalent here,” said Tony Wyss-Coray, an aging expert at Stanford University. “If you just tell people to have fun, that’s OK. But that’s not what they’re saying now.”
In the end, Dr. hopes. Horvath that epigenetic clocks can help scientists find treatments that slow the aging process. Scientists are testing many possibilities in mice and other animals, but it’s hard to know whether successful ones will work in humans. Having a clock that works across all mammals could help bridge the gap.
Researchers have found that some strains of mice live longer if their calories are reduced, for example. Using the universal mammal clock, Dr. Horvath and his colleagues compared 19-month-old mice on a restricted diet to mice of the same age on a normal diet. Mice on a restricted diet had their clocks turned back within four months.
A treatment that mimics calorie restriction in mice may slow biological aging in humans. But warned by Dr. Horvath said his research into the epigenetic clock made him doubt that humans could live beyond the maximum human lifespan of about 120 years.
“It was set in stone during development,” he said.