HHMI: AND WHAT HAVE YOU LEARNED?

EN: We knew that smooth muscle cells arise from a specific kind of progenitor or stem cell that resides within blood vessels. We thought that these progenitor cells generated new smooth muscle cells throughout life. But by studying progeria, we've learned that the progenitor cells can only divide, or double, a finite number of times and then they die. In children with progeria, these cells double only until the children are in their mid-teens. Our working hypothesis is that this early death of the progenitor cells is due to the genetic defect that causes progeria, which was identified by Francis Collins [former head of the National Human Genome Research Institute]. That defect occurs in the gene that makes the protein lamin A, turning it into a defective protein called progerin. And while we haven't worked out the precise molecular mechanisms involved, we think that progerin causes the progenitor cells to die early.

HHMI: HOW IS THIS RELEVANT FOR NORMAL AGING?

EN: A colleague, Tom Misteli at the National Cancer Institute, discovered that as healthy people age, they begin to make progerin. Somehow their normal lamin A gene starts producing this mutant protein. We don't know why this happens, but because we now have the resources from the progeria work—including a mouse model and a tissue bank—we hope we'll be able to puzzle out exactly why older people produce progerin. We think it could be an important clue to understanding many aspects of aging.

Elizabeth Nabel, National Heart, Lung, and Blood Institute director since 2005, is a cardiologist whose lab focuses on molecular, cellular, and genetic mechanisms of vascular diseases.

Interview by Brian Vastag

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