Study links gene to longevity

Scientists have inched closer to one day developing a drug that will extend the human life span.

They’re still not close, mind you, but closer. At least that’s the message in a recent study of the humble roundworm that tackles the mystery behind the only scientifically verified way for creatures to live longer – calorie restriction.

Scientists have long known that in many species, cutting back on calories leads to longer life. Studies have shown that eating 70 percent of the calories normally consumed, while also eating adequate vitamins and other nutrients, extends the life of everything from simple yeasts to mice by about 40 percent. But scientists haven’t known why this happens – whether through improved immune systems, less heart disease or better-working hormones – and if it works in people as well.

In a study published in the journal Nature, Nicholas Bishop and Leonard Guarente of Massachusetts Institute of Technology in Cambridge report the discovery of a brain center in roundworms that seems to answer the “how it works” part of this puzzle.

The roundworm is one of the species that has been shown to get the longevity benefit from caloric restriction. The researchers found that a gene called skn-1b seems essential.

People have forms of this gene, which is thought to play a role in skin formation and remove damaging chemicals from the bloodstream later in life. In roundworms, the gene seems to manifest in the brain through two neurons, or brain cells, called the ASI.

To confirm the neurons’ role in translating diet restrictions into longevity, the scientists used a laser microbeam to kill the cells. Their destruction “completely suppressed” the longevity response, they conclude, meaning that fewer calories no longer meant longer life.

To double-check, they inserted into a fresh batch of roundworms a gene that turns fluorescent. That fluorescent gene allowed scientists to see the neurons at work because it lit up when the skn-1b gene was turned on. As expected, the researchers saw the neurons glow brightly when the worms were subjected to caloric restriction and received the longevity benefit.

“It’s an intriguing study. It will lead to a whole lot more experiments,” says biochemist Brian Kennedy of the University of Washington. The key news is the suggestion that it’s not just the amount of food but the brain’s awareness of food intake that is responsible for the beneficial effects.

“That’s a new way to think about calorie restriction,” Kennedy says.

Scientists have been researching the calorie-longevity link since the 1930s, when researchers at Cornell University in Ithaca, N.Y., showed that rats on a low-calorie diet live twice as long as their normal-diet brethren.

Testing the idea on humans hasn’t yet proven a definite link to longer life. Researchers at Washington University in St. Louis reported last year that volunteers in one longevity-diet study had cardiovascular systems that were much healthier than normal, with 55-year-old study participants reporting blood pressure readings more typical of 20-year-olds. Study volunteers ate as little as 1,400 calories a day rather than the 2,000 or more calories in a typical adult diet.

A related study in Nature, led by Andrew Dillin of the Salk Institute for Biological Studies in La Jolla, Calif., finds that a compound called PH-4, which quiets or increases gene activity, also plays a role in releasing the benefits of caloric restriction in roundworms.

So, that’s good news for roundworms. But what about us mammals?

For us pill-popping humans, researchers say the goal is to create a drug over the next decades that mimics the hormonal cascade or fools a mammalian brain center into facilitating longevity.

“I wouldn’t say it is time for people to get excited about a magic pill,” cautions Kennedy. “But (this kind of research) is the only way we are going to find out how calorie restriction works.”