SCIENCE OF AGING
December 1, 2005

Some scientists have discovered a set of "anti-aging" genes in animals that -- when manipulated -- have similar life-extending effects as calorie-restrictive diets. Correspondent Tom Bearden reports on the research into the relationship between genes and aging. This report originally aired Feb. 28, 2005 The NewsHour Science Unit is funded, in part, by a grant from the National Science Foundation.

 

Online NewsHour Special Reports: Science of Aging Other Science Reports Extended Interviews: Dr. Stephen Helfand Dr. David Sinclair Eri Gentry July 14, 2004: A report on the challenges and potential benefits surrounding the sometimes overlooked area of adult stem cell research. Feb. 16, 2004: The director of the National Institutes of Health is spearheading efforts to speed up the time it takes for laboratory discoveries to be translated into new medical treatments and drugs. Browse the NewsHour's coverage of science   News for Students: Science and Technology     Harvard Medical School Division of Aging University of Connecticut Center on Aging Calorie Restriction Society	TOM BEARDEN: When Eri Gentry buys groceries, she's shopping with a lot more than the next week's meals in mind. A couple of years ago, Gentry, an undergraduate at Yale, abandoned conventional eating habits and began restricting her intake of calories to between 1,100 and 1,300 calories a day, about two-thirds of what she'd previously consumed. She did that after reading about scientific research showing that laboratory animals on calorie-restricted diets tended to live longer, in some cases, a lot longer. Her shopping cart was heavy on vegetables and fruits: Collard and broccoli, apples and oranges, but was balanced out with eggs, yogurt, and nuts. She says it's a healthy, nutritious diet. Gentry also joined the Calorie Restriction Society, a worldwide group whose members hope that following the same diet might extend their lives, too. ERI GENTRY: It was the only type of diet consistently proven to increase your health biomarkers. And it seems that there's a strong case that humans can live longer through calorie restriction and that seems amazing. TOM BEARDEN: Seventy years ago scientists first discovered that rodents kept on a carefully balanced but calorie-restricted diet, lived longer, healthier lives on average than control animals on a normal diet. Later research showed the same thing happened to every animal tested. The research has now gotten as far as monkeys. But no one understood exactly why restricting calories seemed to extend life. Some scientists now believe that new research indicates genes are the controlling factor in the process. They've identified a series of genes with a bewildering variety of names that have similar structures, even though they're found in many different plants and animals. All seem to control the aging process. Some of those discoveries were made by David Sinclair at the Harvard Medical School.
	Anti-aging discoveries
	DAVID SINCLAIR: We used to think that aging was a lot like -- as if we were cars -- we're made fresh and youthful and then we eventually just break down and die. What we didn't realize until recently is that we're much more complex than a car. We fix ourselves if we're broken. And we found that there are particular genes that protect us against aging and if we can tap into these genes, we would have a way of protecting ourselves against the aging process. TOM BEARDEN: Scientists suspect these anti-aging genes must have developed in primitive animals millions of years ago. They think that organisms under stress, like not having enough to eat, activate a kind of cellular survival mechanism, which apparently helps fend off disease, and hence, the animals live longer. Sinclair thinks it's a kind of a cellular emergency response. DAVID SINCLAIR: We think of these longevity genes a bit like a 911 command center, where these genes respond to stressors and maybe a lack of food and they send out the troops, like the ambulance, the fire brigade, to help the cells survive, to hunker down and get through the lean period. TOM BEARDEN: Sinclair and others began looking for ways to turn on the anti-aging genes without restricting the animal's diet, hoping to extend life without reducing caloric intake. He began by working with common baker's yeast. Because a yeast cell grown in a broth of nutrients in a Petri dish lives only 10 days, it doesn't take long to measure lengthened life span. A year ago, researchers isolated a gene called NPT1 and learned that it controls the activity level of a second gene called SIR2. They discovered that artificially stepping up NPT1 activity stimulated SIR2, and caused yeast cells on normal nutrients to live an average of 40 percent longer, just as if they'd been on restricted calories. As research continued, the genes were found in many organisms. University of Connecticut researcher Stephen Helfand found similar genes in fruit flies, another widely studied lab animal with a short life span.
	Observing the genes in action
	STEPHEN HELFAND: So this is a mutation that's been introduced into the fly and we'll have it live longer and we'll have it, we believe, behave as if it thinks it's calorically restricted. TOM BEARDEN: By breeding different kinds of flies and counting the number of flies that die each day, Helfand and his colleague Blanka Rogina found that flies with higher levels of the SIR2 gene also lived longer, even on normal calories. He also found the process worked in reverse. STEPHEN HELFAND: We changed SIR2, we can change life span. We prevent SIR2 from increasing, we can block the life span extension. So it seems as though when we block the ability of SIR2 to increase, we block the ability of calorie restriction to extend life span. TOM BEARDEN: So it SIR2 the key to aging? STEPHEN HELFAND: (Laughs) Well I know people that would like to believe that. Certainly there's a number of pieces of data that suggest SIR2 is one of the central regulators of this process. TOM BEARDEN: The studies gained validity when experimenters found that the same class of genes could also extend life span in another widely used lab animal -- a microscopic worm known scientifically as C. Elegans. Now Sinclair's lab is starting to experiment with mice. DAVID SINCLAIR: Most biologists will tell you a yeast cell and a fly are more distant from each other than a fly is to a human. So we've already jumped a huge distance in terms of biology and we're just filling in the last little gap between flies, mice and people.
	Foods that have the same effect
	TOM BEARDEN: Working together, Helfand and Sinclair also found resveratrol, a chemical found in red wine and peanuts. It seems to target the aging genes specifically, putting them into overdrive and lengthening life span in many lab animals. Sinclair helped found a biotech company to try to turn these discoveries into drugs that could activate the survival mechanism in humans without calorie restriction. It might delay or perhaps even prevent the onset of the diseases of aging, like diabetes, Alzheimer's and others. TOM BEARDEN: In effect, are we talking about tricking the organism into thinking it's under stress? DAVID SINCLAIR: Yeah, that's exactly right. What we're on about here is to trick the animal into thinking that it is calorie restricted. TOM BEARDEN: Neither Sinclair nor Helfand is looking for a fountain of youth pill. But both are optimistic about longer term gains. STEPHEN HELFAND: The idea that you could extend the healthy portion of a life span, and also the maximal life span, I think is entirely possible. In fact, that's what's extended in calorie-restricted mice and rats. DAVID SINCLAIR: Let's admit that people have claimed that they've had the elixir of youth probably for the last 40,000 or more years. So I don't want to claim that we have the cure for aging by any means, but it's really clear that modern medicine, modern molecular biology has finally grasped a potential way to manipulate life span and have a dramatic impact on health care. TOM BEARDEN: In the absence of new pharmaceutical miracles, Eri Gentry plans to continue her calorie-restricted lifestyle. Scientists doing aging research think her diet could have some benefits, but don't believe most people have the stamina to follow such a demanding regimen long term. They hope that what they're discovering with genes and simple organisms will one day help humans live longer, healthier lives without drastic calorie restriction. JIM LEHRER: To participate in an online forum about anti-aging genes, visit our Web site at pbs.org.

The NewsHour Science Unit is funded by a grant from: The National Science Foundation. Reports are produced solely by the NewsHour and do not necessarily reflect the views of the NSF.