Last year, the scientists who created Dolly the cloned sheep raised the concern that she was aging prematurely. Their fear was prompted by the finding that protective tips on her chromosomes seemed shorter than normal for a lamb her age. A new study of cloned cows counters that disquieting finding, however. It even suggests that cloning can create cells, and perhaps animals, that thrive longer than normal.
In the April 28 Science, Robert P. Lanza of Advanced Cell Technology in Worcester, Mass., and his colleagues report that they’ve cloned cows from aged cells. They find that cells from the clones have longer DNA tips, or telomeres, than the original cells and show other signs of youthfulness.
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One telomere researcher says that the new data should dispel concerns that clones will die earlier than normal. “It provides great reassurance,” says Robert A. Weinberg of the Massachusetts Institute of Technology.
Lanza suggests that his group’s use of cells that have survived a long time may have a benefit. “Cloning from cells with a long life span may lead to animals with a long life span,” he speculates.
Whether the cloned cows will enjoy extra years—and Weinberg expresses skepticism—cells from the animals do keep dividing in lab dishes longer than normal. Achieving the same result with human cells could have important medical benefits. In a strategy called therapeutic cloning, scientists would like to use a person’s DNA to generate immature cells that they could then coax into forming nerve, muscle, heart, liver, or any other needed tissue.
Scientists had been concerned that cells created through therapeutic cloning would exhaust their proliferative ability before producing enough specialized cells. The new findings may eliminate that worry. “The extended life span of [cloned] cells could lead to a billionfold, if not even trillionfold, increase in the number of replacement cells we can use for tissue engineering and transplantation,” says Lanza.
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Questions swirling around Dolly’s telomeres and her true age motivated the new research. Whenever most cells divide, their telomeres shrink, which has led many scientists to view the dwindling tips as a ticking clock that reflects a cell’s age. Some scientists dispute that, however, and others contest that the buildup of aged cells with shrunken telomeres explains the overall aging of an animal.
In their work, Lanza and his colleagues grew cow skin cells in the laboratory. As expected, after about 50 to 60 doublings, the cells became larger and underwent other physical changes marking their entry into a nondividing stage called senescence. Scientists have theorized that this transition occurs when telomeres shrink to a certain length (SN: 1/17/98, p. 37).
To see if senescent cells could be used to make a clone, the investigators transferred the genes from these cells into cow eggs stripped of their DNA. Surprisingly, the success rate proved comparable to cloning experiments that begin with younger cells.
Moreover, when the scientists examined skin cells from the clones, they found that the telomeres were longer than those of the original senescent cells and even longer than those of typical newborn calves. One cloned cow that’s now 2 years old has the telomeres of a calf, says Lanza.
Also, a gene normally turned off in senescent cells was even more active in cells of the clones than in normal young cells. Finally, instead of doubling only 50 to 60 times in lab dishes, cells from the clones divided around 90 times before becoming senescent. Lanza suggests that his team’s use of senescent cells, which represent proven survivors, explains the general boost in cellular longevity in the cloned animals.