It may not be the eternal spring that Ponce de León searched for, but thanks to Steve Horvath PhD, a professor of human genetics and biostatistics at the University of California, Los Angeles, the Fountain of Youth is not as elusive as it once was.
Horvath has developed a biological clock that makes it possible to measure the age of humans via tissue samples. "Many people associate the term 'biological clock' with issues surrounding fertility. Others think of it as a measure of longevity. I simply define a biological clock as a device that measures the passage of time in organs, tissues, and cells, based on biological data," Horvath explains. "The epigenetic clock is by far the most accurate biological clock that I am aware of, and it’s the first that allows one to contrast the ages of different organs and cell types collected from the same person. For example, it can be used to show that the heart tissue of a 50-year-old man is 10 years younger than the rest of his body."
The implications are huge. With more than 100,000 people dying daily from age-related afflictions, this clock could be a useful tool for studying aging, and developing ways to combat cancer and other diseases that are tied to getting older.
Horvath's work falls into an area of genetics called epigenomics, which studies epigenomes, the chemical compounds that modify DNA to tell it what to do. Without these little bosses, your heart cells wouldn't know to be heart cells, and your kidneys would have no clue that they're supposed to filter your blood. The chemical compounds that make up epigenomes are directly related to your environment; they come from things like the food you eat and the medications you take. One of the ways they deliver orders is through DNA methylation, where chemical tags attach to a DNA molecule and control the way it interacts with a cell's protein-making factory. Changes in DNA methylation occur over time.
So in 2009, when Horvath decided to tackle the arduous process of developing biomarkers of aging, he turned to methylation data. "It has been known for decades that age has a profound effect on DNA methylation levels. So to develop the markers for this biological clock, I studied age effects on functional genomics data including gene expression data and DNA methylation data," Horvath says.
He began by collecting data from open access repositories, which amass DNA research from scientists around the world. The data shed light on nearly 8,000 cell and tissue samples from people of all ages, including specimens from the heart, brain, lungs, and liver. He extracted 39 datasets and used them to create an age predictor that references 353 specific DNA sites in the body where methylation is impacted by age. Then he tested his predictor on another 32 datasets by comparing each tissue's biological age to its chronological age. He also used almost 6,000 cancer tissue samples to study the relationship between cancer and aging.
What he found is that there were some tissues that consistently displayed a different biological age. For example, Horvath discovered that across the board, healthy breast tissue measured two to three years older than the rest of a woman's body. And for women with breast cancer, the tissue adjacent to the tumor was 12 years older and the tumor itself was 36 years ahead of schedule. This advanced tissue age could explain why age is a huge risk factor for developing cancer.
And when he examined pluripotent stem cells—adult cells that have been reprogrammed to an embryonic stem cell-like state—he got another big surprise. "The procedure used for turning mature cells into stem cells resets the epigenetic clock to zero. We are only at the very beginning of what will be a long research endeavor, but this demonstrates that one can turn back the hands of time of this epigenetic clock," he says. Forever young may not be so far behind.