Why do our bodies age at different rates? Why can some people run marathons at the age of 70, while others are forced to use a walker?
Genes are only part of the answer. A trio of scientists from the University of North Carolina argue in a new paper that more work needs to be done on "gerontogens"—factors, including substances in the environment, that can accelerate the aging process.
Possible gerontogens include arsenic in groundwater, benzene in industrial emissions, ultraviolet radiation in sunlight, and the cocktail of 4,000 toxic chemicals in tobacco smoke. Activities may also be included, like ingesting excessive calories, or suffering psychological stress.
Writing in Trends in Molecular Medicine, Jessica Sorrentino, Hanna Sanoff, and Norman Sharpless argue that focusing on such factors would complement more popular approaches like studying molecular changes in old bodies and searching for genes that are linked to long life.
"People have focused on slowing aging, which always struck me as premature," says Sharpless. Even if scientists announced tomorrow that they'd discovered an antiaging pill, he says, people would have to take it for decades.
"Getting [healthy] people to take medicine for a long time is challenging, and there are always side effects," Sharpless says. "If you identify stuff in the environment that affects aging, that's knowledge we could use today."
Frailty and Mental Decline
Twin studies have suggested that only around 25 percent of the variation in the human life span is influenced by genes. The rest must be influenced by other factors, including accidents, injuries, and exposure to substances that accelerate aging.
"The idea that environmental factors can accelerate aging has been around for a while, [but] I agree that the study of gerontogens has lagged behind other areas of aging research," says Judith Campisi of the Buck Institute for Research on Aging.
She adds that scientists have become more interested in these substances in recent years after learning that many types of chemotherapy, and some anti-HIV drugs, can speed the onset of age-related traits like frailty and mental decline.
The quest to identify gerontogens is partly a quest to find better way of measuring biological age. There are several options, each one imperfect.
Researchers could look in the brain and measure levels of beta-amyloid, a protein linked to Alzheimer's disease, but these levels would not reflect aging in other parts of the body.
They could measure the length of telomeres—protective caps at the end of our DNA that wear away with time. But doing so is hard and expensive, and telomere length naturally varies between people of the same age.
Sharpless's team has focused on one particular aspect of aging—a process called senescence, in which cells permanently stop dividing. Senescent cells accumulate as we get older, and they contain ten times the usual levels of a protein called p16.
The team has developed a strain of mice that produce a protein that glows whenever they make p16. "When they get older and have lots of senescent cells, they glow like crazy," says Sharpless. "When you expose them to gerontogens, they'll glow at a younger age than you expect."
The team members are using their mice to test potential gerontogens, and they've sent the animals to around 50 different labs that are doing the same. They're also working with a company called HealthSpan Diagnostics to create a version of their p16 test that could measure biological age in people.
"One marker isn't going to do it. You need a panel," says Sharpless. "The perfect test doesn't exist, but I'm certain that within my lifetime we'll have the ability to measure someone's physiological age with precision."
Sharpless expects the research to change perceptions. "If you did what we've done for carcinogens, where we've tested millions of compounds, you'd find stuff that you'd be really surprised were gerontogens," he says.
Campisi adds, "It might take some time for toxicology agencies to classify environmental exposures as gerontogens." But she notes that it took many decades between developing a good test for carcinogens to the current situation, where hundreds of risk factors have been classified according to their potential for causing cancer. The field of aging is just taking its first steps towards that goal.