Cellular structure linked to aging.

New clues to the cellular basis of aging have emerged from studies of the brewer's yeast Saccharomyces cerevisiae. Last year, scientists isolated a S. cerevisiae gene, SGS1, similar to the human gene responsible for Werner's syndrome--a condition that mimics aspects of aging. Young people with Werner's syndrome acquire gray hair and diseases such as osteoporosis, cataracts, and hardening of the arteries. Like the human gene, SGS1 controls behavior associated with aging, report Leonard Guarente of the Massachusetts Institute of Technology and his colleagues in the Aug. 29 Science.

"The idea is that by figuring out what this gene does, we can find out not only about disease but also about the aging process itself," says Guarente.

When S. cerevisiae divides in two, it splits asymmetrically. Most of the old cellular material remains within the larger--or mother--cell. Researchers obtain a collection of old cells by watching a single yeast cell under the microscope and pushing the daughter cells aside each time a new one emerges.

To analyze yeast containing mutations in SGS1, the scientists counted the number of times a cell divided. They found that alterations in SGS1 shorten the reproductive life of S. cerevisiae. The mutations also cause yeast that have undergone relatively few cell divisions to acquire other defects--such as an inability to mate--that usually affect only old cells. Strains with a short reproductive life due to mutations in genes other than SGS1 did not display such behaviors of old age. Together, these data indicate that many normal activities of aging occur at an accelerated pace in the SGS1 mutants.

Further results point to the nucleolus--the part of the cell nucleus where the machinery for producing proteins is made--as a center for aging-related activities. The SGS1 protein resides in the nucleolus. Moreover, both SGS1 mutants and old normal cells display enlarged and fragmented nucleoli.

"We don't know what happens in humans yet, but this work raises the possibility that there may be important things occurring in the nucleoli," says George M. Martin of the University of Washington Medical School in Seattle.