Key To Aging May Be Found In Heart Muscle Cell Deterioration

January 12, 2005

GAINESVILLE, Fla. — The key to why humans age may be found deep within the heart, a University of Florida researcher says.

A UF study has found that in the heart muscle, one of the two populations of mitochondria deteriorates more quickly, encouraging the production of age-promoting molecules called free radicals. These are formed when oxygen electrons escape during the mitochondria’s energy-producing process.

The findings, which were published in an online journal Jan. 10, shed new light on the complex workings of the body’s most vital organ and may help scientists find a way to halt the natural deterioration that occurs in the heart with aging.

Each year, an estimated 17 million people die worldwide from heart disease, according to the World Health Organization, and it is the leading cause of death in the United States.

Researchers know that heart muscle cells have two specific populations of life-critical mitochondria residing in two distinct locations: one located just below the cell membrane, called subsarcolemmal mitochondria, and those located deep in the muscle fibers, called the interfibrillar mitochondria, or IFM.

“We discovered that within the heart IFM, there were large increases of the antioxidant defenses,” said Christiaan Leeuwenburgh, director of the Biochemistry of Aging Laboratory in UF’s College of Health and Human Performance, who has been studying human aging for about 10 years. “When you are younger, those antioxidants act like the supermen of your life to eliminate the free radicals. With age, the free radicals begin to win the battle.”

“We found that the IFM are more metabolically active, and they appear to work harder,” Leeuwenburgh said. As a result, the IFM age quicker and may be prone to producing more free radicals within the heart muscles, he said.

“Free radical production occurs in younger animals 2 or 3 percent of the time,” Leeuwenburgh said of his findings from the study on rodents. “But as IFM age, that percentage is increased significantly.”

Energy is produced in the mitochondria when particles from consumed food are broken down as they travel on proteins through a process called cell respiration.

The proteins are part of the mitochondria membranes and are responsible for shuttling the electrons removed from the food particles, Leeuwenburgh said. “They are vital components,” he said.

Free radicals attack the proteins, hindering the energy process. When the proteins are damaged, they allow electrons to leak oxides during cell respiration.

“Those oxides form more free radicals,” Leeuwenburgh said. “You get in a cycle where you have more free radicals, and they can damage more proteins. The questions are why is this happening, and why the process is getting less efficient.”

While the focus of Leeuwenburgh’s research was to discover the causes of human aging, he also has focused on resolving the mitochondria damage.

“The human body does have repair mechanisms to correct the damage done by free radicals,” he said. “The body adapts to deal with increasing free radicals, but the defenses lose efficiency with age.”

Antioxidants within the cells provide the defenses against free radical damage, but with age the development of free radicals is happening faster than the body can produce antioxidants to fight them. Leeuwenburgh likened the free radicals to junk accumulating in the heart.

“If there is a lot of junk around, the heart won’t function as well to produce energy,” he said. “But just like the garbage man needs energy to take out the trash, the heart needs energy to remove its junk.”

Through his research, Leeuwenburgh hopes to shed light on why some parts of the heart deteriorate, in an effort to halt these effects. Leeuwenburgh said he chose to research the mitochondria in the heart because of its importance to life, and because some parts of the heart function less efficiently as they age.

“There are certain regions of the heart that really need to push the blood forward, and as you age, those are the areas working the hardest where the IFM deteriorate fastest,” he said.

That, Leeuwenburgh said, is when heart failure occurs.

“In future studies, we want to look at lifelong calorie restriction and lifelong moderate exercise to prevent the breakdown of the IFM,” he said. “The reason we are alive is mitochondria. Discovering how they break down is the first step to understanding the mechanisms of aging.”

Dr. Huber Warner, associate director of the biology of aging program of the National Institute on Aging, said Leeuwenburgh is a leader in the area of research on aging.

“Dr. Leeuwenburgh’s research has been focused on the important question of how damage to cellular components leads to death of those cells and how this ultimately impacts on tissue function during aging,” he said.