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Creosote bush
The desert-dwelling creosote bush could hold an oasis of answers for researchers looking to extend the life span and quality of life for humans.

Prehistoric Plant Sheds Light
on Age-Old Quest

August 2007

by Will Sansom

If you’ve been to the American Southwest, you’ve probably seen it — and smelled it. The scraggly creosote bush, Larrea tridentata, exudes a pungent, sort of sweetish odor, tolerates high desert temperatures, and hoards water for itself with deep root systems and chemical secretions that prevent other plants from growing around it. The parent plants even reproduce themselves to keep the creosote family line going for thousands of years.

Even though the creosote was a horticultural nuisance, Native Americans found it useful. They brewed a tea from the creosote leaves to treat sicknesses including diabetes, the common cold, stomach pains, burns and wounds. A compound from the bush may even have antioxidant and anti-inflammatory properties.

Now the creosote’s medicinal qualities are being put under the microscope as part of a federally funded research program at the Health Science Center’s Sam and Ann Barshop Institute for Longevity and Aging Studies. The National Institute on Aging (NIA) Interventions Testing Program is evaluating compounds in mice to determine whether these agents might one day be given to people to help them stay healthier throughout life.

The NIA selected the Barshop Institute, the Jackson Laboratory in Bar Harbor, Maine, and the University of Michigan to participate in this program. The centers are evaluating compounds that might have age-slowing effects, but have not been proven to possess these effects by a rigidly controlled scientific study.

Among the first group of four compounds studied, nordihydroguiaretic acid (NDGA), an ingredient found in the leaves of the creosote bush, captured the scientists’ attention. Aspirin and two other agents did not demonstrate noteworthy effects.

Each center compared groups of mice fed a diet supplemented with one of the compounds versus a control group fed no supplement. Of the compounds, only NDGA decreased mortality in male mice by the date by which at least half of the male control mice had died at each test site. The lowered mortality was not observed in females.

"This one compound appears to be extending the first half of the life span," said Randy Strong, Ph.D., professor of pharmacology in the Graduate School of Biomedical Sciences. "When half of the untreated animals were dead, we found many fewer male animals were dead in the group fed with NDGA."

Dr. Strong directs the NIA Interventions Testing Program at the Barshop Institute, and James F. Nelson, Ph.D., professor of physiology, is co-director. The NIA awarded $2.5 million to the Barshop Institute for this research. Dr. Strong also is a member of the Geriatric Research, Education and Clinical Center of the South Texas Veterans Health Care System.

NDGA’s effect on reduced mortality was statistically significant at two of the sites, the Barshop Institute and the Jackson Laboratory, and showed a similar, although not statistically significant, trend at the University of Michigan. The scientists do not know why only males were impacted by NDGA.

Dr. Strong noted that the three Interventions Testing Program centers replicated each other’s findings, as the NIA intended. This study marks the first time a compound has been tested and shown to have positive effects on median life span in an animal model at three different centers.

The scientists ensured that the animals studied at each site were genetically diverse enough to mirror a human population. "We know we are not treating some disease specific to an inbred strain of mice," Dr. Strong said.

Barshop Institute Director Arlan G. Richardson, Ph.D., said extending maximum life span of animals is "the holy grail of aging research." However, he also said, "Even if the maximum life span is not longer, the goal is that the animals are healthier longer."

Dr. Richardson is professor of cellular and structural biology at the Health Science Center, senior research career scientist with the South Texas Veterans Health Care System,and holder of the Methodist Hospital Foundation Chair in Aging Studies.

The researchers next will find out whether NDGA extends maximum life span. "We don’t want people starting to take large amounts of NDGA to slow aging," Dr. Strong said. "The U.S. Food and Drug Administration cautioned that NDGA might cause kidney and liver toxicity at very high doses. We don’t have the full life span on these mice. Because older organisms tend to metabolize compounds more slowly, it is possible that NDGA will be toxic at older ages. We will retest this intervention at different doses."

The Barshop Institute is enhancing the quality of aging research and clinical application to help people live longer, healthier lives. Whether improved life in the golden years will be tied someday to a scraggly desert bush remains to be seen. Stay tuned.


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