Happy 120th? Science Pushes Human Longevity

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Insulin signaling ties into the best-known method for increasing lifespan—caloric restriction.

For more than 70 years, scientists have known that animal lifespans can be lengthened proportionately to their decreased caloric intake.

In other words, mice fed 40 percent fewer calories will live, on average, 40 percent longer than mice fed normal diets, and look better besides.

Ingested calories trigger the release of insulin, which stimulates the IGF-1 pathway that seems to promote aging.

Peter DiStefano, chief science officer with Elixir, a Cambridge, Massachusetts-based drug company, cautions that reduced IGF-1 and calorie restriction probably affect aging in different ways.

Nevertheless, both approaches—at least in rodents—increase lifespans, he says.

Might humans respond the same way? Scientists don't know.

UCLA evolutionary biologist John Phelan suggests calorie-reduced diets could increase human lifespans, but not substantially.

In Phelan's view, lean diets extend longevity in mice and other experimental animals chiefly by diminishing their sexual activity. Mice devote tremendous amounts of energy toward reproduction.

But when fed calorie-restricted diets they mate less—liberating energy that allows them to live longer, he says.

Humans, on the other hand, invest less in reproduction, and won't likely achieve the same longevity benefit.

"Our message is that suffering years of misery to remain super-skinny is not going to have a big payoff in terms of a longer life," Phelan said in a recent press statement.

Other researchers aren't so sure. They caution that more data in larger animals are needed.

Donald Ingram, acting chief of the Laboratory for Experimental Gerontology at the National Institute of Aging, investigates the effects of a 30 percent calorie-reduced diet in monkeys, which share many metabolic similarities with humans.

It's too soon to tell if the animals will live longer. (The study began in 1987, and the monkeys' typical lifespan is 40 years). But preliminary indicators show risk factors for age-related disease are reduced among these animals.

"But we just don't know enough yet about how much longer large animals might live on a calorie-restricted diet," Ingram said.

In the meantime, researchers are combing metabolic pathways for drug targets that might prolong human life.

Elixir's DiStefano says the insulin-signaling pathway is especially promising.

The holy grail is a drug that tricks cells into thinking they've been deprived of calories when they haven't. These cells might activate mysterious processes that prolong life, without the need for extreme dieting or its side effects, DiStefano says.

Evolutionary biologist Michael Rose, from the University of California, Irvine, was among the first scientists to postpone aging in animals.

He accomplished this in 1980 by forcing fruit flies to mate only at advanced ages. By selectively breeding the progeny, he produced flies that live twice as long as normal.

When asked about the most plausible methods for prolonging human life, Rose said, "First drugs and then organs cultured using stem cells from your own tissues."

"It's just like cars are better now than they were at the turn of the century," he added. "We'll be able to give you a new body, bit by bit, and pathway by pathway."

"I don't necessarily think anyone should feel they need to live longer, nor do I see life extension as a moral virtue or a societal goal. But I am saying that if it's something you want to do, then we can offer the technical possibilities."

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