[tt] PsyUSA Network: Einstein Researchers Discover Gene Mutations Linked to Longer Lifespans

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Einstein Researchers Discover Gene Mutations Linked to Longer Lifespans
Public release date: 4-Mar-2008
[No URL furnished. Thanks to Lynn for this.]

Contact: Karen Gardner
kgardner at aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine

March 4, 2008 (Bronx, NY) ? Mutations in genes governing an important
cell-signaling pathway influence human longevity, scientists at the
Albert Einstein College of Medicine of Yeshiva University have found.
Their research is described in the March 4 issue of the Proceedings
of the National Academy of Sciences.

The report is the latest finding in the Einstein researchers' ongoing
search for genetic clues to longevity through their study that by now
has recruited more than 450 Ashkenazi (Eastern European) Jews between
the ages of 95 and 110. Descended from a small founder group,
Ashkenazi Jews are more genetically uniform than other groups, making
it easier to spot gene differences that are present. In 2003, this
study resulted in the first two "longevity genes" ever identified?
findings that have since been validated by other research.

The present study focused on genes involved in the action of insulin-
like growth factor (IGF-I), a hormone that in humans is regulated by
human growth hormone. Affecting virtually every cell type in the
body, IGF-I is crucially important for children's growth and
continues contributing to tissue synthesis into adulthood. The IGF-I
cell-signaling pathway is triggered when IGF-I molecules circulating
in blood plasma latch onto receptors on the surface of cells, causing
a signal to be sent to the cell's nucleus that may, for example, tell
that cell to divide.

Animal research had shown that mutations to genes involved in the IGF-
I signaling pathway cause two effects: Affected animals have impaired
growth but also longer life spans. So the Einstein scientists
reasoned that altered signaling in this pathway might also influence
human longevity. To find out, they analyzed IGF-I-related genetic
variations in 384 Ashkenazi Jewish centenarians. And since plasma
levels of IGF-I do not reflect their levels at a younger age, the
researchers also looked at two other groups: the children of these
centenarians, and a control group consisting of Ashkenazi Jews the
same age as the centenarians' children but with no family history of
longevity.

Remarkably, the female children of the centenarians had IGF-I plasma
levels that were 35 percent higher than female controls?perhaps a
sign that the body was compensating for a glitch in IGF-I signaling
by secreting increased amounts of the hormone. That suspicion was
strengthened by two other findings: the daughters of centenarians
were 2.5 cm shorter than female controls; and when the researchers
analyzed the gene coding for the IGF-I cell-surface receptor molecule
to which the IGF-I hormone binds, the receptor genes of centenarians
and their daughters were much more likely to have a variety of
mutations than were the receptor genes of the controls.

"Our findings suggest that, by interfering with IGF-I signaling,
these gene mutations somehow play a role in extending the human life
span, as they do in many other organisms," says Dr. Nir Barzilai,
senior author of the study and director of the Institute for Aging
Research at Einstein.

Dr. Barzilai notes that a drug that decreases IGF-I action is
currently being tested as a cancer treatment and could be useful in
delaying aging. "Since the subjects in our study have been exposed to
their mutations since conception, it is not clear whether people
would need such a therapy throughout life or if it could help people
who received it at a later time."

###

Besides Dr. Barzilai, other Einstein scientists involved in the study
were lead author Yousin Suh, Gil Atzmon and Mi-Ook Cho. Other
researchers were David Hwang, Bingrong Liu and Pinchas Cohen of
UCLA's David Geffen School of Medicine and Daniel J. Leahy of the
Johns Hopkins University School of Medicine.