UT Southwestern researchers find another clue to secrets of cellular aging

DALLAS - June 15, 2001 - A discovery by UT Southwestern Medical Center at Dallas scientists that genes near human telomeres can be silenced may help explain how and why humans age.

Telomeres are repeating sequences of DNA located at the end of each chromosome and are believed to function as a counting mechanism for cellular aging.

Dr. Jerry Shay and Dr. Woodring Wright, UT Southwestern professors of cell biology, report in today's issue of Science that human cells can exhibit telomere position effect (TPE), a mechanism by which genes near telomeres can be turned off, and that the strength of gene silencing is proportional to the length of nearby telomeres.

Shay and Wright, along with collaborators at UT Southwestern, have previously shown that human cells age each time they divide because their telomeres shorten. After a finite number of cell divisions - when telomeres become short - the cells stop dividing.

Most normal cells lack the enzyme telomerase, which maintains telomeres. Telomerase is activated in 90 percent of all cancers, in which cells continue to divide at a high rate. Many diseases, including Down syndrome, are characterized by premature aging. Further understanding of TPE could help researchers discover how cellular aging contributes to the overall aging process.

"This is an important step in trying to explain the connection between telomere shortening and aging," Shay said. "Normal cells will only grow for a limited time. They grow for a while, and then they go through a process called senescence, or aging. We wanted to know about the molecular memory. Are cells counting how many times they divide? We believe the telomeres are the molecular memory."

The researchers incorporated a piece of DNA containing a luciferase (the enzyme that allows fireflies to emit light) gene into human cells and showed that if it became located at the telomere, there was 10 times less luciferase activity than if it was located in th

Contact: Susan Morrison
UT Southwestern Medical Center

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