Jax Lab Researcher Asks: Is Aging Inevitable?

Humans have long been fascinated with the idea of eternal life. Just look at the cross-cultural obsession with vampires, fountains of youth, holy grails. Until recently, cheating death was purely the subject of mythical adventures, but scientists such as Dr. David Harrison at the Jackson Lab are finally bringing longevity into the realm of serious science.

 

Dr. Harrison has worked as a member of the Jackson Lab’s research staff since 1970. With his wife, he has raised three children in a modest ranch house near Hulls Cove. He has a friendly laugh and infectious curiosity and, like many, knows how aging can sneak up on you. “I’m going to be 68 next year, which I guess is old? Funny how that happens. I used to think 30 was so old, but now my own daughter is 36!” Dr. Harrison has dedicated his career to understanding exactly what aging is, on a biological level, and whether it is something we have to accept as inevitable.

His field took root in the early 1930s, when researchers discovered they could significantly extend the life spans of mice by restricting their diets. This “caloric restriction” not only extended life, but the mice maintained much of their health and vitality as they aged. The phenomenon holds true for a host of other species, including fish, dogs, and possibly even humans. But before you decide to skip half your meals, be warned that such a diet comes with serious risks, including infertility, reduced immunity, and potential malnutrition – not to mention being no fun at all.

So researchers have been looking for a drug that can mimic the life-extending effects of caloric restriction without the caloric restriction itself. Dr. Harrison’s team turned their attention to a drug called Rapamycin. Originally isolated in the 1970s from a soil sample found on Easter Island, Rapamycin is currently used primarily to prevent organ transplant rejection. But Rapamycin also affects many other cellular processes, possibly even those controlling longevity during caloric restriction.

To get the best sense of how Rapamycin might affect humans Dr. Harrison’s team had to come up with a good model in which to test the drug. Mice were an obvious choice because they share many genes with humans, have defined life spans of less than three years and, like humans, are mammals. Typically, such studies are done using mice from a single strain. Strains are bred in such as way that the animals are almost clones of each other. That often is critical to a study because scientists want the two groups they are comparing to be as similar as possible. But that also presents a problem. In real populations, humans are not clones and their varied genetic makeup can have a huge impact on how they respond to their environment.

Just think of George Burns, who smoked 20 cigars a day and lived to 100 while Dana Reeve, wife of Christopher Reeve, died of lung cancer at 45, never having smoked a day in her life.

To understand how Rapamycin could potentially affect a broad range of people, it was necessary for scientists to look at a broad range of mice. For that they needed a lot of different mice – and if there is one thing the Jackson Lab has, it’s a lot of mice. Researchers took two groups of 20-month-old (around retirement age in human terms), highly heterogeneous mice (that is, genetically diverse – imagine a subway car in New York City) and fed one group Rapamycin. Those mice lived significantly longer than their counterparts, an equivalent to extending the life expectancy of a person by 10 years. According to Dr. Harrison, “No other intervention has been this effective … on such a diverse population … when started so late in life.”

Of course, success in mice doesn’t necessarily mean the treatment will work in humans. “Mice are not actually little people, they are the best model we have, but still, they’re mice” Dr. Harrison said. There also are safety issues that need to be resolved, and the Harrison team is currently looking more specifically at the potential deleterious effects of the drug.

An obvious question arises from all this: If we can live an extra 10 years, should we? Dr. Harrison isn’t just interested in living longer for the sake of setting records, he is interested in extending people’s “health span,” or the length of time people remain alive and well. “If you could slow down aging, you could slow down a whole bunch of diseases like heart disease, cancer, and diabetes. And maybe Rapamycin can do that,” he said.

Results of his study were published last year in the journal Nature. To learn more about Dr. Harrison and his research, visit www.jax.org.

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