Deciphering these defined pillars of aging is what experts like Sierra believe affect age-related diseases and could help design the genetic, behavioral and pharmacological means to decelerate aging.
Among the seven pillars, one that has inspired much excitement is metabolism, where researchers have been trying to understand why calorie restriction seems to extend the life span in mice and other animals. Is it because metabolizing fewer calories results in less oxidative damage? Could the absence of nutrients trigger certain defense mechanisms that protect the body? According to Sierra, researchers have managed to identify several molecular pathways that, if modified through medicine, could one day mimic the life-expanding effects of calorie restriction in humans, without requiring anyone to eat less.
Another pillar being thoroughly explored is the fallout from long-term chronic inflammation. Ferrucci says centenarians and others who have lived longer, healthier lives often have less inflammation. We know that many age-related diseases involve inflammation, but we don’t yet know why. Nonetheless, interventions targeted to reduce chronic inflammation are also being examined closely.
We can’t shut down inflammation completely, says Ferrucci. Our bodies need the short-term adaptive form, which quickly turns on and off to fight bacteria and remove debris after injuries and infections. “We need to better understand the process on a molecular level to see if we can develop a drug that only targets what’s not working while leaving everything else functional,” he says. “But right now, we are shooting inflammation with a nuclear bomb — and we need to shoot inflammation with a rifle.”
Developing drugs to modify these processes is one area science is investigating, but it gets complex fast. Some anti-inflammatory drugs have been found to extend life in mice, but these drugs can have multiple effects, and it’s not yet clear why they work. The fact that they tackle chronic inflammation could just be one piece of the puzzle, not the whole solution.
The most promising drug so far has been rapamycin, an immunosuppressant often used in organ transplants that’s been shown to extend the life span of mice. “Rapamycin is already used in humans for unrelated things,” says Steven Austad, scientific director of the American Federation for Aging Research and chair of the University of Alabama at Birmingham biology department. “But in mice, it has an unbelievably wide range of effects that you’d never think a single drug could possibly have, ranging from preventing Alzheimer’s and cardiovascular disease to reducing cancer.”
Austad says other medications have shown similar effects on extending mouse life span, including acarbose (a common drug prescribed for Type 2 diabetes), and anti-inflammatory drugs such as masoprocol and basic aspirin. While the research has a long way to go before anything translates to humans, science may finally be on the right path to understanding aging at its core.
“For the first time in history, we have theories, and the technology to measure those phenomena in living humans longitudinally over time,” Austad says. “And I’m certain that in the next 20 years, science will reveal where we need to go.”— MM