No Fountain of Youth for Fibrotic Cells

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By Sarah C. P. Williams
ScienceNOW Daily News
23 April 2007
Researchers have discovered a link between a protein involved in cellular aging and a devastating lung disease. The connection may open up new treatment options for the disorder, pulmonary fibrosis.

Pulmonary fibrosis is a progressive scarring of the lungs, in which the lung walls become so thick and stiff they can no longer transfer oxygen into the bloodstream. Occupational exposure to dust and certain disorders, such as lupus, cause some cases of the disease. But the origin of another fraction of fibrosis cases is unknown--or idiopathic: Here, the disease often runs in families and appears suddenly after age 50. Lung transplants remain one of the only treatment options for these mysterious cases.

Two independent groups of scientists have now linked some of these cases to mutations in genes encoding telomerase, an enzyme that protects the fragile ends of chromosomes, known as telomeres. Every time a cell copies its genetic material to divide, these telomeres shorten. After many cell divisions, the chromosomes get so short that the cell can no longer function. Telomerase slows this down, and with it the aging process. (Cancer cells contain elevated levels of telomerase.)

In experiments described online this week in Proceedings of the National Academy of Sciences, researchers from the University of Texas Southwestern Medical Center in Dallas screened the entire genomes of families with pulmonary fibrosis, looking for mutations common to the disease. The screen returned a number of mutations in the telomerase genes. Lung cells are constantly exposed to toxins and pathogens in the air, and they need to divide frequently to replenish themselves, notes lead author and pulmonary geneticist Christine Kim Garcia. Problems with telomerase could interfere with this ongoing cell division, making the lungs age faster than they should. \"erhaps the loss of crucial cells in the lung that don't have enough telomerase leads to the disease,\" Garcia says.

The findings come on the heels of a March study in the New England Journal of Medicine, which similarly discovered telomerase mutations in fibrosis patients. \"We used a little bit different techniques, but our conclusions were very similar,\" says an author of that study, oncologist Mary Armanios of the Johns Hopkins University School of Medicine in Baltimore, Maryland. Armanios says both papers will give clinicians new directions to explore in treating fibrosis patients.

Although encouraged by the discovery, lung specialist Michael Keane at the University of California, Los Angeles, says many cases of fibrosis remain enigmatic. \"This probably only explains a small subset of patients with pulmonary fibrosis,\" he says. \"I don't think this is the whole story.\" But telomerase researchers emphasize that the study provides another important clue that anything that shortens telomeres can lead to human disease.