BOSTON -- February 26, 1999 -- Mice lacking a gene for making telomeres -- chromosomal elements with a conjectured but controversial role in aging and cancer -- were found to go gray, lose hair faster, and recover less easily from the stress of surgery and chemotherapy than normal animals. They also developed tumors more often and died earlier, a team of Dana-Farber Cancer Institute (DFCI) researchers report in the March 5 Cell.
"Until now no one has shown the phenotypic effect of telomere loss on the aging organism," says Lenhard Rudolph, research associate in medicine at DFCI and Harvard Medical School (HMS), and lead author of the study. Telomeres -- nubs of protein and nucleic acids poised at either end of DNA strands -- are produced during embryonic development. They crumble away as cells mature and divide, suggesting telomere erosion might somehow control aging. But the process had been studied only in cultured cells.
By knocking out one of the genes for a telomere-making complex, telomerase, Ron DePinho, the American Cancer Society professor at DFCI, and his colleagues created successive generations of mice, each with shorter telomeres. Surprisingly, symptoms were not observed in the telomere-deprived newborns. For example, third generation mice displayed symptoms only after they had reached the age of 18 months. Even the most telomere-deficient sixth generation mice had to go through a waiting period, albeit shorter, before symptoms appeared.
In this and other respects, the mouse findings confirm but,
intriguingly, confound expectations about the role of telomeres in aging and
cancer. While telomere shortening is clearly important, it is not sufficient to
bring about the depredations of age. "Something else in the aging organism
cooperates with telomere dysfunction to compromise fitness," says DePinho, who
is also a professor of medicine (genetics) at HMS. What else that is remains
unclear. "That's one of the central q
Contact: Bill Schaller
Harvard Medical School