Scientists already know that very low-calorie diets lengthen the life spans of many kinds of living creatures, from yeast organisms to flies to mice.
However, long life can also come from other biological aberrations, namely mutations that cause low levels of insulin-like growth factor (IGF-1), a hormone produced by the liver, and of growth hormone (GH), a hormone manufactured by the pituitary gland that stimulates growth in children.
People with excess amounts of these hormones (those with giantism) tend to have shorter life spans. They also have a higher incidence of diseases associated with old age, even when they're relatively young.
Now researchers writing in the Feb. 28 issue of Science are putting all this together and suggesting that manipulating the levels or the action of these hormones should be a focus of drug development.
"You go into starvation so you put all your energy into protecting yourself as well as possible until food comes around again," explains Valter D. Longo, the article's corresponding author and an assistant professor of biogerontology at the University of Southern California in Los Angeles. In Darwinian terms, this means you live long enough to procreate during the next time of plenty.
Longo and his colleagues are suggesting scientists search for ways to simulate this protective state, even when food is available, by manipulating hormones.
Some of this research is already under way by the USC group and others, but it isn't likely to come to fruition any time soon, says Paula Bickford, a professor of neurosurgery at the University of South Florida Center for Aging and Brain Repair in Tampa.
"It's in the very early stages," she says. "This is not something that's going to see early stages of drug testing in the near future in my opinion."
The authors describe three main pathways that could provide a target for such an agent.
One idea is based on the fact that dwarf mice lack growth hormone and live 50 percent longer than normal-stature mice. "This is a powerful issue that has not just been demonstrated in one organism, but in all major model systems, so there is a high chance that this is going to work also in humans, at least to a certain degree," Longo says. A drug would act on the mechanisms that control the release of growth hormone. The key here would be to get the long life without the dwarfism or its associated side effects, such as obesity.
The second possibility would be to prevent the liver from secreting as much IGF-1.
Or, you could approach it from another angle and find a way to manipulate the effects of IGF-1 on the cellular structure. In other words, IGF-1 would still be present in normal or close to normal levels in the blood, it just wouldn't be able to hit home as well.
Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein School of Medicine in New York City, is not so sure of the theory.
For one thing, the growth-factor picture is far from clear. "It's a very confusing subject," he says, adding that many anti-aging centers actually give their clients more growth hormone, presumably to stop or reverse aging.
For another thing, Barzilai found slightly elevated IGF levels in a group of 250 centenarians he is studying.
"It's possible that IGF has some role in the longevity of rodents, but whether it has a role in the longevity of humans is not really well-established," he says. "And there's no proof that dwarf humans live longer and certainly centenarians are not dwarfs."