December 9, 2004
La Jolla, CA – Scientists at the Salk Institute have provided a startling insight into how cells age that might lead to new approaches for treating cancer and even aging itself.
Dr. Jan Karlseder, an assistant professor at the Salk Institute for Biological Studies, and his PhD student Laure Crabbe have discovered that a small piece missing from a single chromosome may be sufficient to trigger the aging process. The findings are published today in the journal Science.
Crabbe and Karlseder discovered that people with Werner’s syndrome, a rare genetic disorder in which people age rapidly from the age of about 15 and usually die of cancer by age 40, are missing the protective caps (called telomeres) on the ends of some of their chromosomes. Further investigation revealed that these people are unable to create normal chromosomes during cell division because they lack a crucial protein called WRN. This protein acts as a ‘detangler’ that unravels knots in the DNA during the complicated process of chromosome replication.
Until this discovery, it was generally accepted that aging occurs through a gradual process of genetic attrition in all 46 chromosomes within a cell, whereby the telomeres get shorter and shorter with each cell division throughout life. The theory was that once the telomeres can no longer fully protect the genetic material the resulting genetic damage leads to age-related changes in the cell.
The discovery that the loss of just one or two telomeres is enough to trigger the dramatically accelerated aging and cancer seen in Werner’s syndrome opens up the possibility of intervening in the process.
“Scientifically, the biggest impact is that the dysfunction of a single telomere can lead to aging, and that has not been described before,” said Karlseder. “The wider implication is that in normal people this discovery might lead to new approaches for therapies for cancer and even aging.”
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes.