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Effects of rare, devastating disease linked to shrinking of cells' telomeres

BOSTON - Scientists at Dana-Farber Cancer Institute and their colleagues have found that much of the widespread damage that the rare genetic disease ataxia telangiectasia, or AT, wreaks on the body results from the progressive shortening of telomeres, the structures that cap the ends of a cell's chromosomes.

In genetically altered mice, the researchers found that the shortening of telomeres led to a "crisis" that disrupted chromosomes "like a hand grenade thrown into the cell," as one scientist put it. The resulting cellular chaos was manifested throughout the rodents' bodies by the loss of reparative stem cells that different organs normally have in reserve, producing symptoms of premature aging such as hair loss and slow wound healing, and early death.

The report by Kwok-Kin Wong, MD, PhD, and Ronald A. DePinho, MD, of Dana-Farber and their collaborators was posted by Nature today on its website as an advance online publication, and it will appear in a forthcoming print issue of the journal.

"There are significant implications for humans" in the discovery, said DePinho, whose laboratory has made a number of fundamental findings about telomeres and their role in aging, cancer and problems like liver cirrhosis. "It suggests that much of the problems in AT are related to eroding telomeres. It provides us with a point of attack." For example, it might be possible someday to restore telomere function with drugs and potentially reduce some of the ravages of the disease, DePinho says.

The study advances the understanding of telomeres' implication in fundamental health problems like cancer, organ failure, premature aging and shortened lifespan. The findings also reveal the complexity of this effect and highlight differences between the disease in mice and humans, explains DePinho, who is also on faculty at Brigham and Women's Hospital and Harvard Medical School.

Telomeres are protein structures that protect the ends of linear
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
22-Jan-2003


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