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Of Mice and Men — Solving the Aging Riddle

San Antonio (Feb. 26, 2003) — If real mice could talk like Stuart Little does in his movies, they might say they aren't getting any younger. One can see the tell-tale signs in older mice: reduced activity, brittle bones, loss of appetite, patchy skin, hair loss. Generations of mice bred to age with specific diseases are the stars of aging research, and they demonstrate the ways in which the genes of mammals, including humans, get more and more out of kilter after the reproductive years.

"We are designed to reproduce and our bodies spend considerable energy on it," said Jan Vijg, Ph.D., professor of physiology at the Sam and Ann Barshop Center for Longevity and Aging Studies, a component of the nationally known aging research program at The University of Texas Health Science Center at San Antonio (UTHSCSA). "We are also designed to sustain and repair continuous injuries to our genetic blueprint. We believe that the effectiveness of our bodies in repairing damaged DNA will predict how healthy we are in old age and ultimately how long we live."

Dr. Vijg and Paul Hasty, D.V.M., associate professor at UTHSCSA's Institute of Biotechnology, in collaboration with co-authors from the Lawrence Berkeley National Laboratory in California, Erasmus University in The Netherlands and other institutions, review the scientific literature to date on this subject in the Feb. 28 issue of Science.

The Science paper is titled "Aging and Genome Maintenance: Lessons from the Mouse?" Genome maintenance is accomplished by hundreds of "repair genes." The authors note that even normal animals are not able to repair all the damage to their DNA. Damage accumulates over time — seemingly by design. "Aging underlies a diverse complex of diseases," Dr. Vijg said. "New technologies enable us to exactly mimic human genetic mutations in the genes of mice. We can cause specific genes to be over-activated or under-activated and look at the effects."

Since different mice are as distinct as different people in their genetic makeup, scientists can begin to chart the "phenotypes" or profiles of old age. "Some repair genes work better in my body and others work better in yours, and someone else may have a great combination for longevity," Dr. Vijg said. "We can gradually begin to see which combinations work the best."

More than 150 scientists study aging at UTHSCSA under the auspices of its Aging Research and Education Center. The number of grants UTHSCSA has from the National Institute on Aging is greater than any other medical center in the country.

The Barshop Center currently is located in the university's South Texas Centers for Biology in Medicine, which stands next to the Institute of Biotechnology on UTHSCSA's Texas Research Park Campus. On Feb. 20, leaders including philanthropists Sam and Ann Barshop, who donated $4 million for the Barshop Center, and two U.S. Senators, Kay Bailey Hutchison and John Cornyn, ceremonially broke ground for a permanent home for the Center.

Arlan G. Richardson, Ph.D., is director of both the Aging Research and Education Center and the Barshop Center. "The relationship of cellular aging and genome maintenance will be hotly studied the next 10 years at least," Dr. Richardson said. "The Barshop Center positions us to make even more headway in finding answers."

Contact: Will Sansom