UNC-Chapel Hill team presents new research methods to better understand aging

jprice@newsobserver.comMay 28, 2014 

— A potential reason that one 75-year-old man may be able to play tennis, while another can’t get around without a walker is differences in their previous exposure to toxins such as harsh chemicals or cigarette smoke that may accelerate aging.

In a research paper that sums up their previous studies, three scientists from UNC-Chapel Hill are calling for deeper exploration of “gerontogens” – environmental factors that are thought to prematurely age human cells.

The paper, “Defining the toxicology of aging,” was published online Wednesday in the journal Trends in Molecular Science.

Gerontogens are to aging what carcinogens are to cancer, and learning more about them will lead to a deeper understanding of human aging, said Dr. Norman Sharpless, director of the university’s Lineberger Comprehensive Cancer Center and one of the authors of the paper.

“Most people know that a carcinogen is a chemical that makes you get cancer. But while they are well understood and there are thousands, if not hundreds of thousands of them that are known, gerontogens are not well understood,” Sharpless said. “That’s because we really don’t understand aging as well as cancer, and we haven’t even really had tools to identify them.”

That’s changing. Sharpless’ lab at UNC has developed a mouse that makes it easier to test for what scientists believe is a key marker of cellular aging. UNC has been shipping the animals to researchers in about 50 labs around the world who want to test the effects of various things that are suspected of accelerating or slowing the aging of cells.

The affected tissue in the mice actually glows ever brighter, and in a way that is easily quantified, as “senescent” cells accumulate. Those are cells that have stopped dividing, and which build up in humans as they age.

Sharpless’ team at UNC already has tested the effects of several of these environmental factors on human and mouse cells. Tobacco smoke sped the buildup of senescent cells, as did certain chemotherapy drugs and chronic HIV infections. And ultraviolet rays from the sun accelerated that marker of aging in skin cells.

Exercise protected cells, and to the surprise of the scientists, a high-fat diet didn’t actually cause a serious acceleration in aging, Sharpless said.

The article will clearly provoke much discussion among aging experts, said Peter Hornsby, associate director of the San Antonio Nathan Shock Aging Center and physiology professor at the University of Texas Health Science Center.

The idea that exposures to such things can actually increase the rate of aging, he said, is controversial.

“No one would argue against the idea that bad things in the environment cause diseases; that’s pretty much obvious to everyone,” Hornsby said. “It’s harder to say that things in the environment speed up aging.”

It’s an attractive idea, Hornsby added. “It just would be really hard to prove it because of the fact that people die of all kinds of specific diseases, and if you’re saying they actually are dying of early aging that’s a very interesting idea, but a hard one to prove.”

For instance, tobacco smoke is clearly responsible for not only cancers but for many other diseases that can obviously shorten lives, Hornsby said, but it may not be easy to demonstrate one way or the other they change the rate of aging.

Impacts could be huge

The practical benefits of identifying gerontogens would include helping people age less by generally avoiding them, as they do many carcinogens. For example, when considering two different chemotherapy regimens that are equally effective in fighting breast cancer, doctors may be able to identify and use the one that’s less likely to age the patient by the equivalent of 15 to 20 years, as at least one regimen seems to do.

“Aging may not seem like a big deal if your cancer is lethal and you will be gone in six months,” Sharpless said. “But if you’re going to be cured of your cancer and live another 40 years, then long-term consequences become more important.

“And that’s a population that, fortunately, we are having to deal with more and more,” he said. “Cancer survivors are getting more and more common because we’re getting very good at treating certain cancers.”

The impacts of a deeper knowledge of gerontogens could be huge. From studies on twins, it’s been shown that perhaps only 30 percent of aging is controlled by genetics, Sharpless said, so the other 70 percent must be caused by events such as injuries and environmental causes.

The researchers are often asked why they haven’t tested substances that are believed to protect cells from aging, like the antioxidants found in things like green tea, red wine and blueberries. Such tests are much more complicated than they may seem on the surface, Sharpless said, and it just made more sense to spread the mice to a host of other labs with their own specializations.

Much of the public’s interest in aging has focused on how to slow it. Sharpless said that he believes scientists will identify such things as research into cellular aging grows.

Identifying substances that healthy people can avoid is likely to have a greater public health impact, though, he said.

“As a physician, I can tell you it’s hard to get healthy people to take a drug for 20 years,” he said. “But if you tell them to avoid cigarette smoke or ozone or benzene in the water, I think that they’re much more likely to do that.”

It will take not only tests like those using the mice, but a battery of others that will have to be developed to give scientists a fuller picture of the effects of environment on molecular aging, he said, but that should happen in the next few decades.

For now, there are at least some basic facts.

“Everybody in the field writes an anti-aging book at some point,” Sharpless said. “These books are, like, 300 pages long and have this exotic advice about what kinds of vitamins and things to use. I always joke that one day I’m going to write mine and it’s going to be very short. It’s going to say, don’t smoke, have good genes – pick parents who are healthy late in life. It’s going to say stay thin because being very overweight is bad for you. And it’s going to say exercise.”

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