UA professors search for fountain of youth

Eric M. Jukelevics Arizona Daily Wildcat Public Health Professor Ron Watson speaks yesterday in the Flandrau Planetarium about a new peptide-based therapy to boost the immune system. The new therapy developed by the UA College of Medicine could allow people infected with the HIV virus to maintain good health without ever developing the symptoms associated with AIDS.

"If you can't eat a half pound of broccoli every day, you can take Vitamin E supplements," public health professor Ron Watson said to about 20 people yesterday during his "AIDS and Aging: Potential Breakthroughs and Treatments" lecture at Flandrau Science Center and Planetarium.

Many people believe nothing can be done about aging because of intrinsic human DNA properties, Watson said. University of Arizona researchers are trying to debunk that theory, he said.

"We believe aging is not a normal life event but a disease that we can treat at least in part," Watson said. "We think if there's some way we can block immune cells from becoming dysfunctional we can treat it."

A human immune system contains T-cells that help fight infection.

During the aging process - and as the HIV virus progresses into AIDS - the activity of one type of T-cell increases, sup-pressing the function and number of others.

"It's like racing an engine," Watson said. "If you continue to step on the accelerator it damages the engine."

Healthy immune systems contain 1,000 T-cells per square millimeter of blood, he said. When that number decreases to 200 or 100 - common in AIDS patients - the system is considered dysfunctional and a person becomes more susceptible to diseases. T-cells decrease with age, but not to the level associated with AIDS.

Watson conducted a study that found ingestion of antioxidants and the adrenal hormone Dehydroepiandrosterone helps balance immune cell levels in aging and murine-AIDS-infected mice.

"This imbalance can make health worse," said Jeongmin Lee, a nutritional immunology graduate student who helped conduct Watson's study. "We want to reverse the imbalance."

During a lifetime, production of the adrenal hormone decreases and incidents of cancer and heart disease increase.

"In AIDS patients the DHEA (Dehydro-epiandrosterone) level is like that of 70 or 80- year-olds," Watson said.

In aging and AIDS-infected bodies, more oxidants and fewer antioxidants appear in the blood, he said after the speech.

Watson said he thinks there is a connection between immune dysfunction and DHEA reduction. Adding antioxidants balances increases in oxidants, he said.

Watson fed mice a combination of DHEA and antioxidants to see if such a procedure could slow immune system degradation.

"More research in humans is needed but the mouse data is encouraging," he said. "If you can bring the teeter-totter closer to normal, it appears that immune deficiency is reduced."

If T-cell levels are brought up to 500 per square millimeter of blood, the body will benefit, Watson said.

"Your body is wonderful," he said. "If it has just one half as many cells as normal it can still fight off what's out there."

Lee said the results are positive in spite of the need for long-term, large-scale human trials.

"Basically, what we're doing is preventing the HIV infection from progressing to AIDS," he said. "We cannot cure AIDS but we can delay its progress."

While the researchers don't know if immuno imbalances can be corrected in the human AIDS virus, it has been improved in mice AIDS, Lee said.

"In the case of aging we want to give the T-cells more ability to proliferate," he said. "We want to keep the immune system young."

Watson collaborated with John Marchalonis, the UA's microbiology and immunology department head, on another research project that supported his DHEA study results.

That research, which developed the T-cell receptor peptide therapy, involved injecting mice with a unique peptide that was able to keep mice immune systems in balance. A peptide is a fragment of protein consisting of two or more amino acids.

"The reason we looked for a T-cell receptor peptide is that if we could stick in a specific chemical that just blocks that one step (one T-cell's hyperstimulation), and it works it would be a proof of principle type of thing," Watson said. "It worked."

The therapy is being patented by Allergene, a San Mateo, Calif.-based biotechnology company that hopes to test it on HIV-infected humans.

Michael Lafleur can be reached via e-mail at Michael.Lafleur@wildcat.arizona.edu.