Extend Lifespan of Mice
Associated Press Writer
8:20 PM EST; November 17, 1999; (AP) -- Italian scientists have genetically engineered mice to live up to 35 percent longer than normal -- an experiment that offers the strongest evidence yet that aging in mammals is controlled by a genetic switch. The researchers at the European Institute of Oncology in Milan deleted a gene in the mice that makes them vulnerable to cell damage caused by oxygen. Equally important, the mice suffered no apparent side effects.
Other scientists called the study a major step forward in understanding the aging process. The study was published in Thursday's issue of the journal Nature. "They hit a milestone in aging research with this study -- they've found a genetic intervention in mice that make them live longer without any side effects," said Leonard Guarente of the Massachusetts Institute of Technology. Genetic control of longevity had already been confirmed in worms and flies, but not in mammals, which have their own aging process. "We now know for sure that longevity is genetically controlled," said the study's author, Pier Giuseppe Pelicci. Researchers bred the mice without a gene that produces protein vulnerable to cell damage from oxidation.
The findings could mark a departure from one of the basic rules of biology -- namely, that if you tinker with a gene or other factor in an animal to add some kind of benefit, it usually comes at a cost somewhere else. For example, scientists can increase mouse longevity by about 30 percent by tightly restricting diet and slowing down the metabolism, but it comes at a cost of decreased fertility and size. The Italian researchers could find no other problems with the mutant mice, though Pelicci admitted that the gene's entire function is unknown, so problems could still arise. The researchers are now investigating the possibility of blocking the age-controlling protein chemically, which could lead to the development of life-extending drugs. But Pelicci warned: "How many times have we found something in mice that was not the case in humans?" Oxidation has been suspected in aging since 1956, when it was first proposed that free radicals -- unstable molecules with an unpaired electron -- attack cells. Oxidative damage has been implicated in forms of cancer and in heart disease.
Joe McCord of the Webb-Waring Institute for Biomedical Research at the University of Colorado, who in 1969 helped prove that oxidation was involved in cell damage, called the Italian study "fascinating and very significant," but noted that oxidation also regulates beneficial cellular functions as well as destructive ones. "The balance that works best in the laboratory may not be the best balance if the animal is dealing with wound healing and infections and other kinds of stress," he said.