Scientists Draw Back Veil on the Mystery of Aging : Medicine: Success in extending animals’ lives through ‘Methuselah’ genes may lead to longer human life span.
A growing body of animal evidence suggests that it eventually may be possible to extend normal human life spans beyond the currently accepted norm of about 70 years.
Findings presented Friday give new perspective to the mystery of aging, a research field that has yielded only isolated clues over the years. But recently the findings of scientists have begun to mesh with one another.
At a meeting of the American Assn. for the Advancement of Science, scientists from California and Colorado reported that they have been able to extend the life spans of fruit flies and the common roundworm by manipulation of what some call “Methuselah” genes.
Intriguingly, one of these genes seems to operate by the same mechanism as the caloric restriction that many scientists, including UCLA pathologist Roy Walford, have shown will increase the life span of rodents and even some primates. Until recently, such restriction of food intake was the only way known to extend life spans.
That gene is the blueprint for an enzyme that destroys highly reactive molecules called free radicals, which form naturally in the body and are thought to speed aging by hastening the breakdown of normal cells. The new work suggests that eventually the life span of humans could be manipulated by drugs or genetic engineering.
“Aging is something that we can manipulate, analyze and understand,” said UC Irvine biologist Michael R. Rose. “Aging can be changed.”
In fact, Rose and his colleagues have been able to double the life span of flies, giving them the equivalent of a human life span of 150 years. They achieved this by reversing the rules for natural selection, which is the fundamental basis for the process of evolution.
Evolution typically favors members of a species that reproduce at an early age. Early reproduction increases the odds that the parent-to-be will have eluded death by predators or disease and hence that their genes will be passed on. But an abundance of evidence shows that delaying reproduction actually prolongs life, according to evolutionary biologist Steven N. Austad of Harvard University.
By genetic manipulation in crossbreeding experiments, Rose and his colleagues repeatedly delayed the reproduction of flies and their offspring until later in life than usual. After multiple generations, they found that the average life span of the flies had increased by 80%.
They also found that they could increase life span by restricting the amount of food the flies ate and, separately, by exposing the flies to extreme environmental stress and mating only those who survived.
In addition, the researchers found that the flies with the extended life spans had unusually high concentrations of an enzyme called superoxide dismutase, or SOD, which breaks down the age-inducing free radicals. Many researchers believe caloric restriction prolongs life by reducing the number of free radicals formed from food, so the two approaches appear to be complementary.
Further evidence of the importance of SOD was presented here by molecular biologist James E. Fleming of the Linus Pauling Institute of Science & Medicine in Palo Alto, Calif. Fleming used genetic engineering techniques to insert extra copies of the gene for SOD--one of the Methuselah genes--into fruit fly embryos and found that the flies lived as long as Rose’s.
Molecular geneticist Thomas E. Johnson of the University of Colorado has been studying a completely different system, but has obtained surprisingly similar results. He works with the common roundworm, Caenorhabditis elegans, an extremely simple organism with a normal life span of about three weeks. He has found that he can double the life span of the worms by chemically mutating another Methuselah gene, which he calls “age-1.”
Roundworms with the mutated gene reproduce at a later age than normal roundworms and have fewer offspring. Johnson originally thought that was why they lived longer. Recently, however, he has found that the roundworms with the mutated age-1 gene have an increased ability to destroy free radicals.
This suggests that a normal age-1 gene may limit life span by suppressing the SOD Methuselah gene and that it may be possible eventually find drugs that will block age-1, prolonging life. If a similar gene exists in humans, he added, then the drug would also prolong their lives.
Rose said human life span could probably also be extended by using genetic engineering techniques to insert the SOD gene into blood cells. But because of the potential ethical dilemmas involved in gene therapy, such a possibility seems highly unlikely.
