Science of Determining the Age of Mammals - Summer 2023

NEW YORK, NY.- Susannah Woodruff can’t wait to stop pulling teeth out of polar bears.

Woodruff, a wildlife biologist at the U.S. Fish and Wildlife Service, keeps tabs on Alaska’s population of the bears. She 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 producing cubs.

Until recently, the only reliable way to determine the age of a polar bear has been to extract a premolar and inspect its growth rings. “No researcher wants to do it,” Woodruff said in an interview Monday, just before embarking on a trip to Alaska’s North Slope.

This really comes under the heading of recognizing how little we know about the planet we live on. We can now determine the age of mammals by analyzing chemical tags. While we admire progress and how smart we are, one would hope a little humility might for a moment cause one to wonder what else we don’t know.

On this trip, rather than pull teeth, she will merely draw blood. Using a method known as the epigenetic clock, she and her colleagues will be able to estimate the bears’ ages by analyzing chemical tags on their DNA. She and her colleagues have recently found that using this method gives an estimate within a year of the bears’ true ages, making it more accurate than examining teeth.

The clock’s implications go far beyond polar bears. On Thursday, an international team of scientists published a study in the journal Nature Aging showing that epigenetic clocks tick inside 185 different species of mammals, including people. 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 its speed determines how long a species can live.

“You have a bat, you have a whale — with completely different ecologies — but you can use the same math formula to measure aging,” said Steve Horvath, who led both of the new studies as a principal investigator at Altos Labs, a biotech company based in the San Francisco Bay Area. “It’s completely stunning.”

The epigenetic clock is made possible thanks to millions of small molecules called methyl groups that are bound to our DNA like Christmas lights on a wire. When a cell divides, the DNA in the two new cells typically ends up with the same, distinctive pattern of methyl groups. But our cells also have enzymes that can pry methyl groups off the DNA.

Scientists have known about methylation for decades, but they’re still trying to figure out exactly what its purpose is. It most likely has something to do with keeping genes active or silenced. Adding methyl groups around a gene may be a step in shutting it off, while removing them may be involved in turning the gene back on.

In the 1960s, Soviet scientists noticed that as salmon grew old, their DNA became less methylated. In later years, a few studies found a similar pattern in other species. And other research found that certain regions of DNA get extra methyl groups with age.

In the early 2010s, Horvath, then at the University of California, Los Angeles, wondered whether he could predict the age of an organism from its methylation pattern alone. He fed a computer with methylation data from thousands of human cells. Horvath then trained the machine to use that data to predict the age of the people from whom the cells came.

Horvath reported in 2013 that a computer needed to examine just 353 spots in the DNA of a cell to make a guess that was within a few years of a person’s chronological age. In the decade since, he and others have tried to build even more accurate epigenetic clocks. The 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.

Still, there’s a lot about epigenetic clocks that scientists don’t yet understand. “We know it’s working, 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 whether the epigenetic clock reveals anything that can make a difference medically. “I am still waiting to be convinced that the metric generated has any value,” said Dr. John Greally, an epigenetics expert at the Albert Einstein College of Medicine in New York.

Horvath and his colleagues have responded to the skeptics by looking for a deeper molecular understanding of the clock. In the new project, Horvath contacted biologists who study mammals and asked for blood and tissues to examine. They sent him materials from hundreds of species.

The scientists trained a computer to create a new clock that could predict the age of animals based on a single epigenetic pattern across species. It was able to make good predictions about the ages of 185 species by looking at fewer than 1,000 spots in mammal DNA.

This finding means that biologists may be able to estimate the ages of animals far more easily than in the past — not just polar bears, but any wild mammal. As the technology matures, researchers hope to switch from blood to saliva or perhaps feces, which could be gathered in less invasive ways.

“This is a major breakthrough in the field and a fascinating and important discovery,” said João Pedro de Magalhães, an expert on aging at the University of Birmingham who was not involved in the study. De Magalhães predicted that it would not only help biologists more accurately estimate the age of wild animals, but also help to decipher why all mammals — including us — get old.

The early results from epigenetic clocks have also created a new marketplace. A number of 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’s a lot of shenanigans and snake-oil sellers who tried to make money off this, and the epigenetic clock field is certainly rampant with it,” said Tony Wyss-Coray, an aging expert at Stanford University. “If you just tell people it’s for fun, that’s OK. But that’s not what they say right now.”

Ultimately, Horvath hopes that epigenetic clocks will 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 if the successful ones will also 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 cut back, for example. Using the universal mammal clock, Horvath and his colleagues have compared 19-month-old mice on a restricted diet to mice of the same age on a normal diet. The mice on a restricted diet had their clock turned back four months.

A treatment that mimics calorie restriction in mice might someday let people slow down their pace of biological aging. But Horvath cautioned that his research on the epigenetic clock made him doubt that people would ever live past the maximum human life span of about 120 years.

“It’s set in stone during development,” he said.

This article originally appeared in The New York Times. https://artdaily.cc/news/161309/How-old-is-that-polar-bear--The-answer-is-in-its-blood-