Barshop Institute, other NIA-funded centers spotlighted

Posted: Wednesday, May 30, 2007
Contact: Will Sansom
Phone: 210-567-2579

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Three American research groups, including scientists from the Sam and Ann Barshop Institute for Longevity and Aging Studies at The University of Texas Health Science Center at San Antonio, will announce interim findings this week of the first round of compounds studied in the National Institute on Aging (NIA) Interventions Testing Program.

The scientists will convene Friday, June 1, in San Antonio at a pre-conference session of the 36th annual meeting of the American Aging Association, which is June 2-4. Nordihydroguiaretic acid (NDGA), a compound that is found in the leaves of the desert creosote bush, will be the center of discussion.

Comparison of diets, effects
Four compounds, including the creosote bush ingredient and aspirin, were studied for age-slowing effects in mice at NIA-funded centers at the Barshop Institute, where Randy Strong, Ph.D., directs the NIA program; the Jackson Laboratory in Bar Harbor, Maine, directed by David Harrison, Ph.D.; and the University of Michigan, directed by Richard Miller, M.D., Ph.D. 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, an ingredient in tea made from leaves of the creosote bush, decreased mortality in male intervention-group mice on 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 early part of the life span, and at the median part of the life span, when half of untreated animals were dead, we found many fewer animals were dead in the group fed with NDGA,” said Dr. Strong, also a professor in the Health Science Center’s department of pharmacology.

Strength of results
Dr. Strong noted that the three Interventions Testing Program centers replicated each other’s findings, as the NIA intended. 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.

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. “We each have our own animal colony, we were each feeding the same compounds, we are in different parts of the country,” Dr. Strong said. “Sometimes we see effects by chance, where a treatment extends the life span in an animal model, but then nobody can repeat it. This is not that.”

The animals studied are a four-way cross, which ensures no two animals are genetically identical and the colonies at each site are more like a human population. “We know we are not treating some disease specific to an inbred strain of mice,” Dr. Strong said. “Rather, these mice carry disease susceptibility of four different strains. So if we see an effect, it is not something unique to only one strain of mice.”

‘Holy grail of aging research’
Barshop Institute Director Arlan G. Richardson, Ph.D., said: “The holy grail of aging research is to find something that doesn’t just increase the median life span but also increases the maximum life span. The other goal is to try to increase the health span of animals. 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 scientist with the South Texas Veterans Health Care System, and holder of the Methodist Hospital Foundation Chair in Aging Studies at the Health Science Center.

“Recent genetic initiatives have allowed researchers to identify many leads to extending life span and, maybe more importantly, improving health span,” said Felipe Sierra, Ph.D., director of the Biology of Aging Program at the NIA. “Studies supported by the Interventions Testing Program provide a vital link to possible human application of these discoveries by identifying compounds that affect the activity of the genetic pathways in mice in a way that positively affects the aging process.”

This summer, the researchers will find out whether NDGA extends the maximum life span, Dr. Strong said.

Uses and cautions
Native Americans used the creosote leaves to treat sicknesses including diabetes. One previous research study suggested the compound’s usefulness in treating mice that are engineered to develop the neurodegenerative disease amyotrophic lateral sclerosis, or ALS. The creosote bush ingredient also appears to have antioxidant and anti-inflammatory properties.

“We don’t want people starting to take large amounts of this stuff to slow aging,” Dr. Strong cautioned. “We don’t have the full life span on these mice. The U.S. Food and Drug Administration put out a caution that NDGA might cause liver toxicity at very high doses. We will retest this intervention at different doses. If it doesn’t extend maximum life span, we will ask why. For instance, we will want to know how well this compound is metabolized at older ages, whether it builds to toxic levels that shorten the maximal lifespan. We will be interested in how it is working, what it is doing. We have collected preliminary data on immune function, behavior and hormone levels. We will want to look at other characteristics of these animals to see if they really show signs of slowed aging.”

Dr. Strong is director and James F. Nelson, Ph.D., professor of physiology, is co-director of the NIA Testing Interventions Program site at the Barshop Institute. The NIA awarded $2.5 million to the Barshop Institute in 2004 for this research.

Aspirin, meanwhile, produced a small but statistically insignificant effect on life span, Dr. Strong said.

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The University of Texas Health Science Center at San Antonio is the leading research institution in South Texas and one of the major health sciences universities in the world. With an operating budget of $536 million, the Health Science Center is the chief catalyst for the $14.3 billion biosciences and health care sector in San Antonio’s economy. The Health Science Center has had an estimated $35 billion impact on the region since inception and has expanded to six campuses in San Antonio, Laredo, Harlingen and Edinburg. More than 22,000 graduates (physicians, dentists, nurses, scientists and allied health professionals) serve in their fields, including many in Texas. Health Science Center faculty are international leaders in cancer, cardiovascular disease, diabetes, aging, stroke prevention, kidney disease, orthopaedics, research imaging, transplant surgery, psychiatry and clinical neurosciences, pain management, genetics, nursing, allied health, dentistry and many other fields.

The Barshop Institute of The University of Texas Health Science Center at San Antonio is dedicated to enhancing the quality of gerontological research and clinical application, with the ultimate goal of providing humankind with longer lives, free of debilitating disease.

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