( tatus of the telomerase gene says Grei...)A little telomerase isn't enough

"If you were to search for the genetic mutation behind this mouse's disease, you wouldn't find it -- there isn't one," says Greider. "These mice develop disease only because their telomeres are short, and having telomerase doesn't lengthen them right away."

The condition of the mice is virtually identical to the human disease dyskeratosis congenita, which has already been linked to mutations in telomerase that hinder the protein's telomere-maintaining activity. In both mice and people with the condition, stem cells in bone marrow that replenish the blood cells and those in the digestive system that maintain the intestines can't divide as many times as they should and die early.

Because sperm and egg arise from stem cells, too, their telomeres gradually shorten, and each successive generation starts out with chromosomes whose telomeres are even shorter than their parents, the researchers report. The failure of telomerase to lengthen these telomeres explains why successive generations develop the physical symptoms of the disease at younger ages than their parents or grandparents, say the researchers.

In the Proceedings of the National Academy of Sciences in October 2005, Greider and her team reported their study of one family with dyskeratosis congenita. Mary Armanios, M.D., now an assistant professor of oncology in the Johns Hopkins Kimmel Cancer Center, discovered that the family carried a genetic defect that caused the telomerase protein to be half as effective as normal and that shortening telomeres were to blame for earlier onset.

In this family, the affected grandmother developed gray hair in her 20s and lung problems in her early 60s and died at age 65. Her affected children developed signs of the disease about 10 years earlier than she had, and analysis of their cells revealed that 60 percent to 75 percent of their chromosomes had dangerously short telomeres. In an affected g
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Source:Johns Hopkins Medical Institutions