Aging has long been recognized as the worst risk factor for chronic ailments like atherosclerosis, which clogs arteries and leads to heart attacks and stroke. Yet, the mechanism by which aging promotes the clogging of arteries has remained an enigma.

Scientists at Duke University Medical Center have discovered that a major problem with aging is an unexpected failure of the bone marrow to produce progenitor cells that are needed to repair and rejuvenate arteries exposed to such environmental risks as smoking or caloric abuse.

The researchers demonstrated that an age-related loss of particular stem cells that continually repair blood vessel damage is critical to determining the onset and progression of atherosclerosis, which causes arteries to clog and become less elastic. When atherosclerosis affects arteries supplying the heart with oxygen and nutrients, it causes coronary artery disease and puts patients at a much higher risk for a heart attack.

The researchers' novel view of atherosclerosis, based on experiments in mice, constitutes a potential new avenue in the treatment of one of the leading causes of death and illness in the U.S., they said. Just as importantly, they continued, this loss of rejuvenating cells could be implicated in a broad range of age-related disorders, ranging from rheumatoid arthritis to chronic liver disease.

The results of the Duke research were posted early (July 14, 2003) on the Web site of the journal Circulation at http://circ.ahajournals.org. The study appeared in the July 29, 2003, issue of the journal.

The researchers believe that it might ultimately be possible to forestall or even prevent the development of atherosclerosis by injecting these particular stem cells into patients, or to induce the patient's own stem cells to differentiate into progenitor cells capable of arterial repair.

"Our studies indicate that the inability of bone marrow to produce progenitor cells, which repair and rejuvenate the lining of the arteries, drives the process of atherosclerosis and the formation of plaques in the arteries," said Duke cardiologist Pascal Goldschmidt, MD, chair of the Department of Medicine. "For a long time we've known that aging is an important risk factor for coronary artery disease, and we've also known that this disease can be triggered by smoking, bad diet, diabetes, high blood pressure, and other factors.

"But if you compare someone who is over 60 with someone who is 20 with the same risk factors, there is obviously something else going on as well," he continued. "The possibility that stem cells may be involved is a completely new piece of the puzzle that had not been anticipated or appreciated before. These findings could be the clue to help us explain why atherosclerosis complications like heart attacks and strokes are almost exclusively diseases of older people."

Doris Taylor, PhD, a senior member of the research team, sees these findings leading researchers into new areas of investigation.

"For the first time we are beginning to get an insight into how aging and heart disease fit together—we've known they go hand-in-hand—but we haven't understood why," she said. "Understanding that we either run out of progenitor cells or that they don't work as well is a big molecular clue to what might be going on in the whole aging process."

Other members of the Duke research team included: Frederick Rauscher, MD, Bryce Davis, Tao Wang, MD, PhD, Priya Ramaswami, Anne Pippen, David Gregg, MD, Brian Annex, MD, and Chunming Dong, MD.