In a study published in the Nov. 1 issue of the Journal of Clinical Investigation, the researchers report that as cells and tissues age, the expression of two proteins called p16INK4a and ARF dramatically increases. This increase in expression, more than a hundredfold in some tissues, suggests a strong link between cellular aging and the upregulation, or increased production, of p16INK4a and ARF.

"At the very least, our work suggests that looking at the expression of one or both proteins will make a great biomarker of aging - a tool to clinically determine the actual molecular age of people, as opposed to just their chronological age," said Lineberger member Dr. Norman Sharpless, the senior author of the study and assistant professor of medicine and genetics at UNC's School of Medicine.

"We all know people that we consider to be a young 65, and we believe they won't demonstrate as much p16INK4a or ARF expression as others of the same age."

In addition to identifying molecular targets that may slow aging in the future, the study may also suggest immediate clinical applications. Knowing the molecular age of a tissue may also enable physicians to select the "youngest" most viable tissues and organs for transplantation, to predict how well a patient will heal after surgery and, by being able to characterize the regenerative ability of a patient's bone marrow, predict future toxicity of chemotherapy in a cancer patient.

Both p16INK4a and ARF are known potent tumor suppressors, or proteins that halt tumor cell growth. The study suggests that the important anti-cancer function of these proteins to limit cellular growth might in turn cause aging.

"Proliferation of cells is important in th
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Contact: Leslie H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
4-Nov-2004