Iowa Researchers Identify Possible Reason For Rare, Accelerated Aging Condition

UI researchers have found that people with progeria have extremely low levels of antioxidant enzymes. Progeria is a disease that mimics normal aging but occurs at a very fast pace. The antioxidant enzymes, deficient in individuals with progeria, protect most people against cell-damaging free radicals known as reactive oxygen species (ROS).

"Understanding the molecular mechanism underlying progeria may help to further explain the molecular basis of normal aging, " said Larry Oberley, Ph.D., UI professor of radiology and the study's lead investigator.

Progeria cells are ideal for the study of aging because they mimic the aging process without the time it would take in normal models. Investigating the process would require three years in mice and 40 years in monkeys, Oberley said. The progeria research, by contrast, took three months.

In their investigation, the UI researchers found that progeria cells demonstrate only 50 percent of normal catalase activity and 30 percent of normal glutathione peroxidase activity. Catalase and glutathione peroxidase are two of the four primary antioxidant enzymes. The lack of these two enzymes makes it impossible for the cells to effectively remove toxic peroxides produced during normal cell metabolism.

Reintroducing antioxidant enzymes into the cells may halt or reverse the problem. To accomplish this, the UI investigators plan to use adenovirus gene transfers. This approach involves attaching the enzymes to a disabled common cold virus and then giving it to patients. The virus, acting as a transporter, takes the enzymes to the necessary cells.

Manipulating antioxidant enzymes might be beneficial for treating a number of diseases. As Oberley explained, "Everything in a cell is about balance." In some cases, such as progeria, adding antioxidant enzymes restores the balance, allowing the cell to live. In other cases, such as cancer, adding the enzymes disrupts the balance, causing the cells to die.

"You use the same reagents, just in different ways," Oberley said. "We're just on the edge of radical medical advancement. We're talking about possible treatments for cancer, aging, heart attacks -- most of the diseases of mankind."

UI researchers plan to use their gene transfer strategy to try to treat some of these other conditions.

The UI progeria findings are included in a recent issue of Biochemical and Biophysical Research Communications. The National Institutes of Health provided funding for the research.