Originally created 04/28/00

Age doth not wither nor custom stale cow clone cells



Unlike Dolly the sheep, cloning of cows does not seem to speed up the aging process of cells, according to a new study.

Robert Lanza of Advanced Cell Technologies of Worcester, Mass., and colleagues report Friday in the journal Science that the cells from six healthy cloned cows actually seem to appear to be even younger than cells from normal cows of the same age.

Lanza said it's unclear how cloning helps the cells escape the signs of aging, or whether this will translate into a longer lifespan for the animals. But it does show that the process of inserting genetic blueprints from one animal into the egg of another doesn't automatically shorten the lifespan of cells in the clone.

The celebrated cloned sheep Dolly seemed older than her age, with chromosomes that were shorter than those of normal sheep the same age, suggesting that she had "inherited" the age of her genetic mother.

Cells are able to divide only a limited number of times. When it can no longer divide, a cell dies. To create the cow clones, the researchers had used cells that were near the end of their lifespans, with only a few rounds of division still to go.

But when the cells were cloned, the clock seems to have reset for the six cows. Instead of being zero to four division cycles away from oblivion, the cells taken from the cows proved to have more than 90 division cycles to go.

Cells display their age with wear and tear on the telomeres, the caps at the end of chromosomes that keep their genetic threads from unraveling each time the cell divides. Telomeres usually can't repair themselves, so they are slowly worn down as divisions occur.

But where Dolly's telomeres were short, the chromosomes from the cloned cow sisters are youthful, actually longer than those found in normal cows of the same age.

"It's really remarkable," Lanza said. "Telomeres from all of the cows, including one who is celebrating her first birthday this week, look like those of a newborn."

The finding is critical, because among the major applications expected from cloning technology are replacement tissues for humans and extended breeding years for farm animals.

It's still uncertain whether the clones will actually live longer than ordinary cows born at the same time, or whether the aging process will somehow catch up with the animals later. The researchers are continuing efforts to understand how cloning reprograms the timetable for cells.

But even if cloning doesn't turn out to be a fountain of youth, the study brings the prospect of replacement tissues and genetically engineered organ replacements from animals a big step further from science fiction.

"The extra population doublings of these cells means that we could get a billionfold increase in the number of replacement cells that can be used for tissue engineering and transplant therapies," Lanza said. "This could have profound ramifications for alleviating our current organ donor shortage."

Lanza and his team suggest that several differences in cloning techniques between Dolly and their cows may account for the more youthful clones.

Dolly's genetic material came from a mammary cell that had been starved and put into a resting state. The cows' material came from cells near the end of their lifespans, and from connective tissue cells.

"Previous studies have indicated that there may be variation in how different cell types repair telomeres, which could make the choice of donor cell significant," Lanza said.

On the Web:

http://www.sciencemag.org.