One of the rarest diseases in the world is progeria. It is known to exist in only 100 children, causing them to age rapidly—looking 60 years of age when they're 10. They eventually die in their early teens. Elizabeth G. Nabel, director of the National Heart, Lung, and Blood Institute, says research on this rare disorder may offer to help these children, provide insights into normal aging, and furnish information about one of our biggest killers, heart disease.
HHMI: HOW CAN STUDYING RARE DISEASES LEAD TO BROADER DISCOVERIES?
EN: By sorting through the molecular and genetic mechanisms involved in rare diseases, we can learn a great deal of biology that has implications for common diseases. For example, by studying progeria, we are learning about the biology of smooth muscle cells, which line the blood vessels. This has important implications for many vascular diseases that affect millions of Americans.
HHMI: YOUR RESEARCH AREA IS ATHEROSCLEROSIS. HOW DID YOU GET INVOLVED IN STUDYING PROGERIA?
EN: Children with progeria uniformly die of heart attack or stroke in their early teens. But there were few pathology reports on the cardiovascular aspects of progeria. Nothing was really known. When two groups working on progeria asked me to join them, I was really intrigued.
For the past 20 years, I'd been studying smooth muscle cells, the cells that proliferate in atherosclerosis and eventually cause heart attacks and stroke. These smooth muscle cells, we learned, also play a key role in progeria.
HHMI: AT THE BEGINNING OF THE PROJECT, DID YOU THINK YOU MIGHT LEARN SOMETHING ABOUT NORMAL AGING?
EN: Initially, we just wanted to understand this rare disorder. But I quickly realized that understanding progeria would provide a window into understanding atherosclerosis that occurs with aging. The signal feature of blood vessel disease in progeria is a loss of the smooth muscle cells in the arteries. When these cells die, the blood vessels become scarred and inflexible. Eventually, the normal artery is replaced by a stiff, fibrotic tube that can no longer constrict or dilate. The coronary blood vessels can't respond to blood flow demands and a heart attack follows.
This process in progeria is a little different from the atherosclerosis that occurs during aging. In fact, you can think of them as opposite processes with similar results. In progeria, smooth muscle cells die. But in normal atherosclerosis, smooth muscle cells proliferate in a chronic, inflammatory condition caused by high levels of low-density lipoprotein, nicotine, diabetes, high blood pressure, and other things. But because cell growth and cell death are intimately connected, studying one provides insight into the other.
Photo: Paul Fetters