September 2004

University of Southern California

Punching the timeclock of life

Is human longevity programmed? A USC molecular geneticist's findings may one day alter Darwin's ideas

Ten years ago, Valter Longo had an inkling of a theory of aging that is now challenging the dogma of one of science's heavyweights – Charles Darwin.

From graduate school to a career as an assistant professor in the USC Leonard Davis School of Gerontology and the USC College of Letters, Arts and Sciences, Longo's ideas were questioned by peers and students alike as he explored a new way to look at aging that directly opposes principles set forth by Darwin in his theory of natural selection.

It has long been accepted that natural selection happens on the individual level – the better suited an organism is to its environment, the more likely it is to reproduce, forcing the species to change, or evolve, over time.

Longo's theory, in contrast, hinges on a process called "group selection," believed by most scientists to be wrong because it proposes that selection happens at the group level rather than the individual .



The gerontologist also rejects the commonly accepted theory that aging happens by chance and that, like a car, an organism runs well until it starts to breaks down and eventually just stops working. In research published in the Sept. 27 edition of the Journal of Cell Biology, Longo proposes that aging is programmed so that the majority of a population dies prematurely to provide nutrients for the sake of a few individuals who have acquired the genetic mutations that increase their chances of reproduction.

The research is based on observations of programmed aging in baker's yeast by Longo and co-author Paola Fabrizio. Scientists use baker's yeast to study aging because the molecular pathway that regulates its longevity is similar to that in other organisms, such as mice and possibly humans, Longo said.

"Basically, it is the first demonstration, to our knowledge, that aging is programmed and altruistic," Longo said.

"The organisms we have studied die long before they have to in order to provide nutrients for 'mutants' generated within their own population. Thus, billions of organisms die early so that a few better-adapted individuals can grow."

What is even more striking, he said, is that the findings raise the possibility that the same process happens in humans, with many of us dying before we have to.

"Programmed human aging is just a possibility. We don't know whether it's true yet or not," he said. "But if aging is programmed in yeast, and the pathway is very similar, then isn't it possible that humans also die earlier than they have to?"

Longo said he realizes that this theory goes against the fundamental theories of evolution, which is why he took 10 years to publish, combing through scientific papers dating back to the 1870s to learn about the genesis of the theory of natural selection and speaking with prominent evolutionary biologists about his ideas.

"I wanted them to tell me, 'No, you're wrong and here's why.' I never got that," he said.

Longo said there are many questions that have yet to be answered through theoretical studies and a closer look at aging in humans and mammals.

"We're not saying Darwin was wrong. We're just saying that there appear to be some big missing pieces in his theory," Longo said.

"We're also not saying that humans are, for sure, undergoing programmed aging. But, most likely, most organisms undergo programmed longevity. Life is programmed. Whether death is programmed or not is yet to be determined."






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