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These Genes Extend Life and
Protect Against Cancer
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new research reported in the journal "Nature Genetics" identifies naturally occurring
processes that allow many genes to both slow aging and protect against cancer in
the much-studied C. elegans roundworm.
Many of the worm genes have counterparts in humans, suggesting that new
drugs may some day ensure a long, cancer-free life. The new research and a
related study the scientists reported in "Science" last year indicate that cellular
changes leading to longevity antagonize tumor cell growth.
The studies are by scientists at the University of California, San Francisco,
who say the research also underscores the deep evolutionary connection
between lifespan and cancer.
The worms, known formally as Caenorhabditis elegans, were the stars of a
startling 1993 discovery by UCSF biologist Cynthia Kenyon, PhD. She found
then that a change in just one gene, called daf-2, doubled the worms' lifespan.
This finding led to the understanding that lifespan is regulated by genes and
is therefore changeable, rather than the inevitable result of the body's
breakdown. The discovery in worms has been confirmed in other animals
including mice.
The new research by Kenyon and graduate student Julie Pinkston is reported
in the advanced online edition of the journal.
Kenyon is the American Cancer Society Professor and director of the Hillblom
Center for the Biology of Aging at UCSF.
"This is very exciting," Kenyon said. "There is a widely held view that any
mechanism that slows aging would probably stimulate tumor growth. But we
found many genes that increase lifespan, but slow tumor growth. Humans
have versions of many of these genes, so this work may lead to treatments
that keep us youthful and cancer-free much longer than normal."
Since her early finding that the gene daf-2 and another gene known as daf-16
regulate lifespan, Kenyon's research team has hoped to identify the genes
that they in turn affect -- those that more directly affect aging and tumor growth.
"Now we are really getting there," Kenyon said.
The gene daf-2 codes for a receptor for insulin and also for an insulin-like
protein that promotes growth. It influences daf-16, which makes a so-called
transcription factor - a protein that determines when and where hundreds of
other genes are turned on. The focus of the new study was to identify specific
genes regulated by daf-16 which affect cancer and/or lifespan.
The scientists used an established tumor model in the worms. Then, starting
with a list of 734 genes known to be targets of daf-16, they identified 29 genes
that either promote or suppress tumor cell growth. They did this using several
techniques, including RNA interference or RNAi, a powerful tool that allows
scientists to control the expression of just one kind of gene at a time.
About half of the genes stimulated tumor growth and half suppressed it, they
found. Strikingly, about half of these genes also affect lifespan in animals that
do not have tumors, further strengthening the model Kenyon and others have
conceived in which the insulin receptor, daf-2, works in concert with the
transcription factor daf-16 to link longevity and tumor resistance. The
"downstream" genes appear to act in a cumulative way, they found.
The genes that stimulated tumor growth also accelerated aging itself, and the
genes that prevented tumor growth slowed down the aging process and
extended lifespan. These findings greatly strengthen the view that the controls
of lifespan and cancer have deep, common roots, Kenyon and Pinkston
conclude. (Source: University of California - San Francisco
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