'Cell Suicide' A Possible Culprit In Heart Disease, UF Study Finds

GAINESVILLE, Fla. — Scientists have known for years that the heart is one of the first organs to show the ravages of time. Now, two University of Florida researchers say they know why: cell suicide.

In a study published in the February issue of the American Journal of Physiology, researchers at UF’s College of Health and Human Performance attempted to determine why heart cells in older rodents die at much higher rates than those of their younger counterparts.

The process is known as apoptosis. It’s what happens when a cell orders itself to stop functioning, shrink, and ultimately dissolve. Although apoptosis plays a critical role in removing unwanted and potentially dangerous cells, such as tumor cells, excessive apoptosis may contribute to the decline in cardiovascular function with age, said Christiaan Leeuwenburgh, director of UF’s Biochemistry of Aging Laboratory and one of the study authors.

Establishing a link between apoptosis and the development of heart disease is paramount, researchers say, because heart disease is the leading cause of death in the United States, according to the Centers for Disease Control. Heart disease killed 700,000 Americans in 1998, the most recent year for which statistics are available, according to the CDC.

In their study, Leeuwenburgh and Sharon Phaneuf, a third-year doctoral student, obtained hearts from 6-, 16- and 24-month-old rats and isolated the heart cells’ mitochondria, which helps supply the cell with energy. In human terms, the rats would have been roughly 20, 55 and 75 years old.

The scientists studied cytochrome c, a mitochondrial electron transporter that becomes a signal for cell death if it is released from the mitochondria. Phaneuf found the hearts of older animals released greater amounts of that cell-death signal than did the hearts of younger animals and may be partly responsible for the increase in cell death.

“We found that in normal aging, there appear to be alterations in key mitochondrial proteins called Bcl-2 proteins (proteins that control cytochrome c release), which could explain the cell death in the heart,” said Phaneuf. “We looked at what changes were occurring, what particular pathways might be relevant and looked to see what might be done to prevent that.”

Quantifying apoptosis is difficult, but estimates show a healthy elderly male without heart disease or high blood pressure loses 30 percent of his heart cells, said Leeuwenburgh, an assistant health and human performance professor and faculty associate for the UF’s Institute on Aging.

Leeuwenburgh and Phaneuf attribute the disorder to oxidative stress, a condition in which cells have too many free radicals — destructive, highly reactive molecules — and not enough antioxidants, which counteract the damaging effects of aging.

“We are interested in studying the heart because heart tissue is highly prone to oxidative stress and mitochondrial dysfunction,” Leeuwenburgh said.

Leeuwenburgh and Phaneuf say the keys to stopping cell loss before it starts are regular exercise, a balanced diet and eating more antioxidant-rich foods, such as oranges, tomatoes, broccoli and leafy greens.

“We are working on testing whether lifelong, moderate exercise can prevent oxidative stress and therefore excessive cell death with age,” Phaneuf said.

The National Institute on Aging and the Society for Geriatric Cardiology co-funded the study.