Newswise — Researchers have
discovered that the loss of a gene called p63 accelerates aging in
mice. Similar versions of the gene are present in many organisms,
including humans. Therefore, the p63 gene is likely to play a
fundamental biological role in aging-related processes.
"To study how the p63 gene works,
we devised a system for eliminating it from adult mouse tissues.
What struck us right away was that these p63 deficient mice were
aging prematurely," says Alea Mills of Cold Spring Harbor
laboratory, who led the research.
Mice that are born without the p63
gene do not survive. Therefore, Mills had previously conducted
extensive studies of mice that are born with only one copy of the
gene. Still, these animals die at a young age. So to study p63
function in adults, Mills and her colleagues devised a sophisticated
molecular genetic technique that enabled them to eliminate both
copies of the gene from particular tissues including skin and other
multi-layered epithelial tissues after the animals reached maturity.
The effects of premature aging
observed in these p63 deficient mice (image available on request)
were hair loss, reduced fitness and body weight, progressive
curvature of the spine, and a shortened lifespan.
"Aging and cancer are two sides of
the same coin. In one case, cells stop dividing and in the other,
they can't stop dividing. We suspect that having the right amount of
the p63 protein in the right cells at the right time creates a
balance that enables organisms to live relatively cancer-free for a
reasonably long time," says Mills, who adds that this is the first
time the p63 gene has been implicated in aging.
"I first presented these results
at a meeting in Tuscany. I don't want to sound flippant, but if you
have to grow old somewhere, that's about as good a place as any to
do it," says Mills.
The study is published in the
September issue of the journal Genes & Development (advance
online publication August 17). The other researchers involved in the
study were Scott Lowe, Ying Wu, Xuecui Guo, and first author William
Keyes of Cold Spring Harbor Laboratory, and Hannes Vogel of Stanford
University.
Researchers who did not
participate in the study but are familiar with its findings include:
Carol Prives (Columbia
University); Judith Campisi (Lawrence Berkeley National Laboratory);
David Lane (University of Dundee); Lawrence Donehower (Baylor
College of Medicine)
