OREGON STATE UNIVERSITY

Major grant to focus research on aging, disease processes

10/09/2003

CORVALLIS - The Linus Pauling Institute at Oregon State University has received a five-year, $5.8 million grant from the National Institutes of Health that will open new doors to research on aging, cardiovascular disease, and neurodegenerative problems such as amyotrophic lateral sclerosis, or Lou Gehrig's Disease.

The funding will also lead to the designation of this pioneering institute as an NIH Center of Excellence for Research on Complementary and Alternative Medicine.

In a three-pronged approach, the LPI scientists will examine ways in which oxidative or nitrative stress in the body may lead to different health problems as far ranging as the vascular inflammation that can cause heart disease and stroke, the motor neuron collapse typical of ALS, or the slow but inexorable mental and physical declines associated with aging.

A better fundamental understanding of these biological processes, which have widely different results but may share similar biochemical underpinnings, could eventually lead to new ways to prevent or treat diseases that affect millions of people worldwide, scientists say, or prolong the length or quality of human life.

"There is strong evidence that oxidative and nitrative stress in the body can cause damage to certain target molecules and later manifests itself as a specific disease," said Balz Frei, professor and director of the Linus Pauling Institute. "This major commitment from the NIH to research in this area should enable us to make a great deal of progress in understanding the biology of these processes at a very basic, molecular level."

Frei will collaborate on this grant with Joe Beckman, holder of the Ava Helen Pauling Chair at OSU and director of the Environmental Health Sciences Center; and Tory Hagen, an associate professor of biochemistry and principal investigator with the Linus Pauling Institute, who is an international leader on the molecular basis of the aging process.

Increased federal support for research of this type, Frei said, is partly a result of increasing public interest in natural approaches to health and the value of diet in prevention and treatment of disease. These trends led the NIH to create the National Center for Complementary and Alternative Medicine, which this year funded the first three major national "program project grants" of this type to do research in this field.

The Linus Pauling Institute was a natural choice for one of the grants, Frei said, because of its pioneering research on micronutrients, vitamins and phytochemicals in disease prevention and optimal health.

The OSU researchers will pursue research in three major projects. But a common thread running through the research is the potential of certain compounds, especially the powerful antioxidant alpha lipoic acid, to restore a more normal cellular environment and reduce impairments in the function of membranes, lipoproteins, enzymes and genes. The research will also explore the value of metal chelators such as the compound EDTA which is used in chelation therapy, a controversial blood treatment to remove excess iron and heavy metals from the circulatory system; and the role of certain compounds, including uric acid, that are of interest in the treatment of Lou Gehrig's Disease.

"Aging, like disease, is multifactorial in nature, but there appears to be a common underlying theme - a decreased ability of cells and tissues to respond to and recover from stress, such as toxicological or oxidative and nitrative stresses," Frei said. "Loss of stress resistance decreases the ability to ward off pathogens, and increases the likelihood of chronic disease, such as atherosclerosis, cancer and neurodegenerative disease."

Much of the work done in this field, however, has yet to outline the mechanisms of action or adequately demonstrate the health benefits of use of antioxidants or other compounds, the researchers say. The OSU studies will help fill that gap in knowledge, and determine in animal models if some of these approaches merit more attention in the treatment of ALS and heart disease or improving the aging process.

Some preliminary studies are promising. Hagen has published studies showing that treatments with lipoic acid can reverse some of the effects of age-related decline in rats, and Beckman has outlined a complex biochemical reaction taking place in the death of motor neurons related to ALS. Frei, together with LPI research assistant professor Wei-Jian Zhang, has published some leading studies about the inhibition by lipoic acid and metal chelators of cellular adhesion molecule expression and arterial wall inflammation that can initiate atherosclerosis.

This grant is another major step forward for the work at OSU of the Linus Pauling Institute, which came to the university in 1996. The institute has built upon the interests of the late Linus Pauling, an OSU alumnus and two-time Nobel laureate, who founded the institute three decades ago to study the molecular basis by which vitamins and micronutrients can aid in disease prevention and treatment.