Researchers studying a rare genetic form of accelerated aging in humans have reproduced the phenomenon in yeast. The work, published in tomorrow's issue of Science, may help researchers trace out the molecular changes that underlie aging in humans as well as in yeast. It suggests, for example, that a hitherto poorly understood part of the cell called the nucleolus may be a key site of some of those changes.
A team led by biologist Leonard Guarente of the Massachusetts Institute of Technology performed the yeast experiments in order to explore the function of the gene at fault in Werner's syndrome, which causes people to age more than twice as fast as they normally do. They approached the problem by inducing a mutation in the comparable gene in the brewer's yeast, Saccharomyces cerevisiae.
You may not have known that yeast cells age, but they do. After dividing about 25 times, the normal yeast cell stops dividing and dies. While yeast may not get gray hair and wrinkles, they do show signs of middle age; halfway through life they become sterile, stop having sex, and get dramatically larger. The Guarente team found that the mutation they introduced accelerated this process, causing yeast to age more than twice as fast as they usually do--just like humans with Werner's syndrome. "Everything [shortens] to scale," says Guarente. "That's just what you would expect in premature aging. The life-span is about 10 divisions, and at about five divisions, they are becoming sterile."
The Guarente team's work also suggests that whatever the protein encoded by the normal form of the Werner's gene does to stave off premature aging, it does it in the nucleolus, a specialized part of the nucleus where ribosomal genes are transcribed to make the protein-synthesizing machines known as ribosomes. When they stained yeast nuclei with an antibody to Sgs1, the yeast counterpart of the Werner's protein, they found the protein in the nucleolus. That finding fits nicely with recent work from Guarente's lab and elsewhere suggesting that several other proteins act in some way on the nucleolus to slow down aging, as well as with the Guarente team's recent observation that the nucleolus breaks into fragments in very old yeast cells.
"It is a beautiful piece of science," says pathologist George Martin, who studies Werner's syndrome at the University of Washington School of Medicine in Seattle. "It brings attention to the possible role of ... ribosomal [genes], and how instability there may play a role in aging." But Martin cautions that because the advanced aging in Werner's syndrome differs from normal aging in several respects, the Werner's gene isn't necessarily a key to normal aging. Nevertheless, the nucleolus is certain to become a hot spot of aging research.