Headlines
As reported by The Hartford Courant, November 16, 2004.
Adding Life to Years
By William Hathaway
Scientists who investigate why we age don't claim to be able to disarm the Grim Reaper. They have, however, become much more confident that their work someday will help ward off some of the blows of aging - such as diabetes, cancer and dementia.
"We may find out that what have been considered normal parts of the aging process may not have to happen at all," says Stephen Helfand, professor of genetics and developmental biology at the University of Connecticut Health Center in Farmington.
Helfand and other longevity researchers now understand pretty well why restricting calories extends the lifespan of every organism studied so far. They understand it well enough that they no longer have to starve mice, flies, and worms to get them to live longer.
For instance, in one recent study Helfand and UConn colleague Blanka Rogina detailed the multifaceted role of a single gene that extends the life of the fruit fly Drosophila.
By simply activating the gene Sir2, Helfand and Rogina extended the average lifespan of their flies by 57 percent, according to the study, published last month in the Proceedings of the National Academy of Science. They also did two experiments that suggest Sir2 - which is involved in regulating the activity of other genes and proteins, is crucial to increasing lifespan when diet is restricted.
Several other intriguing findings suggest how Sir2 works. Helfand and Rogina report that Sir2 is primarily found in the insect equivalent of fat cells and brain cells. This limited arena of Sir2 activity is just one more piece of evidence that the molecular secret to a long and healthy life might rest in our heads and stomachs.
Increased longevity has been linked to energy metabolism, such as the effects of the hormone insulin. Helfand has managed to double the lifespan of his flies to about 80 days, about twice their normal age. But that is chump change compared with the extra days bestowed upon worms by scientists at the University of California, San Francisco.
Cynthia Kenyon, a professor of biochemistry and biophysics at UCSF, has raised C. elegans round worms that crawl around energetically at age 140 days - nearly seven times the worms' normal lifespan. What she has focused in on is the significant role played by certain genes involved in insulin signaling - known as Daf genes.
Insulin's importance in longevity was reinforced last year when Dr. C. Ronald Kahn, president and director of the Joslin Diabetes Center in Boston, managed to increase the lifespan of mice by simply knocking out the insulin receptors on their fat cells. Mice without insulin receptors on their fat cells not only lived longer, they also were leaner than control mice despite consuming the same number of calories. Researchers continue to aggressively pursue the possibility that some of these same principles might work in humans.
Aging is also intimately tied up with reproduction. Calorie-restricted animals tend to be less fertile than their more well-fed peers. So it makes sense that there should be multiple systems governing how long organisms live, some experts say.
"Aging is really a set of processes. They converge and interact with each other," says Donald Ingram, acting chief of the laboratory of experimental gerontology at the National Institute of Aging. "There is a high level of excitement now with aging research. But what I don't like is when people say, 'I've got it. We don't have to look any further."'
Ingram helps oversee experiments on calorie restriction in primates, which after nearly two decades indicate our closest animal cousins living on curtailed diets may in fact be healthier and more likely to live longer than primates that are better fed.
The primate studies also suggest one of the hurdles in aging research: How do researchers design trials in which their subjects could very well outlive them?
But that won't stop companies from trying to use the fruits of longevity research to combat the diseases of aging.
"Aging research has come of age. The key finding is that aging is plastic, that it can be manipulated," says Alan Watson, chief business officer for Elixir Pharmaceuticals Inc. in Cambridge, Mass., a biotechnology company that is trying to capitalize on the work of Kenyon in San Francisco and biologist Lenny Guarente at Massachusetts Institute of Technology. "There is a lot of interest from [large pharmaceutical companies] that was not there two years ago."
Elixir is particularly targeting metabolic disease, a cluster of symptoms including obesity, high blood pressure, high cholesterol and high trigylceride levels.
Some scientists believe that calorie restriction also reduces apoptosis, or cellular suicide, which may make findings from longevity research applicable to treating cancer and the unchecked growth of damaged cells.
Helfand - who emphasizes that his keen interest is not just in adding years to life, but making sure they are healthy additional years - says his own research offers tantalizing hints that knowledge of the aging process may lead to treatments for diseases of aging such as dementia.
When Sir2 is activated only in neurons, but not in other parts of the body, Helfand's fruit flies live as long as they do when Sir2 is also expressed in other parts of the body. Current research suggests that aging seems to be governed by interaction between the neurons in the brain and hormones such as insulin, Helfand says.
"What we don't know is whether the head is the weak link in aging or [if it] is sort of a master control," Helfand says. "The excitement in the field is that these studies offer the possibility of rational therapeutic interventions. It is no longer just philosophical. Now we can get going.
"As my wife says, we hope to add life to years - not just years to life."