Scientists Find Protein to Control Lifespan in Mice
November 18, 1999

By Patricia Reaney

LONDON (Reuters) - Scientists said Wednesday they had
identified a protein that controls stress and life span in
mice that could improve the understanding of disease
and aging in humans.

The finding, by researchers at the European Institute of
Oncology in Milan, Perugia University and New York's Memorial
Sloan-Kettering Cancer Center, is the first time
a protein for stress response and longevity has been
identified in a mammal.

Genetically modified mice without the gene for the protein,
p66shc, lived a third longer than normal mice without any
apparent impact on reproduction -- a key factor in aging -
or other side effects.

``It is the first time a gene has been identified in mammals
which has these two functions,'' Professor Pier Giuseppe
Pelicci, of the European Institute of Oncology, said in a
telephone interview.

Pelicci and his colleagues, whose research is published in the
science journal Nature, found the protein by chance while
studying a gene that mediates cell growth. They realized that
the same gene also controlled the p66shc protein.

The lack of the protein in the mice seemed to strengthen their
resistance to oxidative stress -- cell damage caused by
charged particles -- and aging.

``The most important implication of this study is that now we
know there are proteins which control the cellular response of
oxidative stress,'' said Pelicci.

Oxidative stress accumulates over time. The cell damage it
causes is thought to play a role in the development of major
diseases like cancer.

Pelicci said the findings could open up new avenues of
research such as how to decrease the damage caused by
oxidative stress and its role in aging.

``Since the degeneration of cell function is the first step
toward diseases we might envision a situation where we could
help the cell not get sick. That's an interesting
perspective,'' Pelicci added.

The research also confirms in mammals what earlier research on
worms and flies had shown -- a correlation between increased
resistance to oxidative stress and longevity.

The scientists could not find any defects in the mice which
lacked the protein. Their next step is to try to understand
the function of the protein and the mechanism that induces

``The second question is: can we manipulate the function of
this protein by drugs,'' Pelicci said, adding that he and his
colleagues had already shown that the protein is captivated by
an enzyme which could be a possible drug target.

In a commentary in Nature, Leonard Guarente, of the
Massachusetts Institute of Technology (MIT), said the study
was the first to show that a simple genetic modification may
increase lifespan in a mammal.

``We should therefore look forward to a growing research area
nurtured by, if not the fountain of youth, more than a trickle
of hope,'' he said.