Gene in Yeast May Hold Secret to Aging

Tycho M. Hoogland tycho at hoogland.demon.nl
Fri Aug 29 07:45:43 EST 1997

 Thursday August 28 11:21 PM EDT

Gene in Yeast May Hold Secret to Aging

By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuter) - A gene that yeast and humans have in common may hold
the secret to aging, researchers saidThursday. They said their "pleasantly
shocking" finding could show that getting old tarts in some of the most
basic processes of cells. Leonard Guarente, David Sinclair and colleagues at
the Massachusetts Institute of Technology studied the SGS1 gene in yeast,
which corresponds to the WRN gene in people. Mutations in WRN cause Werner's
syndrome, a disease whose symptoms mimic those of premature aging, including
development of cataracts, osteoporosis and wrinkling. Guarente said his team
set out to find whether the same gene caused yeast to age. "The reason we
did the experiment was to see if by chance we would get a similar effect,
which we did," he said in a telephone interview. "It raises the possibility
that there is a common mechanism underlying aging," he added. "Aging might
lie at the cellular level." Cells taken from the bodies of people with
Werner's divide at about half the rate of normal human cells. Yeast cells
with the corresponding mutation do the same thing. Guarente's group found
the yeast SGS1 gene also responded to mutations with symptoms of aging, such
as sterility and an enlarged and fragmented nucleolus -- the part of the
cell that produces ribosomes. Ribosomal DNA is extremely important -- so
much so that it is repeated all over the genome. Ribosomes are key to
protein synthesis, the basic first step to most bodily functions. "It's the
most highly reiterated DNA in the genome," Guarente said. "It makes all the
protein in the cell." But this is the weakness -- there are many copies, so
if there is a mistake, or mutation, it gets repeated over and over
everywhere. "It's the Achilles heel of the cells," Guarente said. Guarente
said the Werner's protein seemed to be a structural factor in cells. "When
it's not there the whole thing just falls apart,"he said. In aging, damage
accumulates as cells divide over and over again, making occasional mistakes.
The gene for this protein could be a key one damaged, causing the aging
effect. "I think the big thing is a that there is a possible universal
mechanism," Guarente said. "We were really pleasantly shocked." Yeast is
surprisingly similar to humans genetically.
Both belong to a class of living things called eukaryotes -- which are made
of cells with nuclei. Most living things except bacteria are eukaryotes. In
a separate paper also in the journal Science, David Botstein and colleagues
at California's Stanford University said theycompared the yeast genome --
the collection of all its genes -- to the human genome. They said 31 percent
of the yeast genes had homologs, or counterparts in humans. They said yeasts
are very useful models for studying the function of human genes. They are
easy to grow and manipulate and similarities have been found not only in
Werner's sydrome, but for some types of colon cancer and neurofibromatosis,
a hereditary disorder marked by benign tumors on the nerve cells. "There is
ample justification for intensifying efforts to determine the functional
roles of the remaining 60 percent of yeast genes whose function is still not
known," they wrote.
"These yeast genes may represent the most efficient path to understanding
the colon cancer and the aging cause by mutations in their human homologs,"
they concluded.

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