29 April 2000

Cloning Reverses Aging In Cow Cells

by Kate Melville

Cells from six healthy cow clones show no signs of the premature aging reported for Dolly the cloned sheep, researchers say in the 28 April issue of Science. In fact, the cloning process seems to have sent the cow cells into a backwards time warp, making them appear even younger than cells from normal cows of the same age.

Robert P. Lanza of Advanced Cell Technologies of Worcester, Massachusetts and his co-authors on the Science paper say that they still don't know exactly how cloning helps these cells shrug off the signs of aging, or whether this translates into a longer lifespan for the animals themselves. Despite these unsolved mysteries, the finding erases a lingering doubt about the utility of cloned cells by demonstrating that the process doesn't automatically rob cells of a normal lifespan. In fact, say Lanza and colleagues, cloning could supply a crop of youthful cells for a variety of uses, from medical applications like designing and transplanting replacement tissues for the human body to increasing the breeding years of farm animals.

Like the nine lives of a cat, cells possess a finite number of division cycles--a cell's life is at an end when it can no longer divide. To create the cow clones, the researchers used cells that were near the end of this lifespan, with only a few bouts of cell division left. Surprisingly, Lanza and the others discovered that the cloning process seemed to restore the "nine lives" of these cells in the six cows. Instead of being zero to four division cycles away from the end of their lives, cells taken from the cows were more than 90 cycles away from their end.

Cells also betray their age through the wear and tear on their telomeres, the regions at the tips of their chromosomes. Telomeres cap off the ends of each chromosome and keep their genetic threads from fraying and disappearing with each tug that happens when the cell divides itself again. Since most mammalian telomeres can't repair themselves, they are usually slowly worn away over time--shorter telomeres are often found in older cells. Scientists spotted this telltale sign of maturity in Dolly. Her chromosomes were shorter than those of normal sheep of the same age, suggesting that she had inherited the "age" of her genetic mother and was old before her time.

By contrast, chromosomes from the cow sisters are the picture of youth. Telomeres from the clones are actually longer than those from normal cows of the same age, and in most cases even longer than those from newborn calves. Far from being prematurely aged, cells from the cow clones appear to have recaptured and even prolonged their youth, lengthening their lifespan beyond that expected for their chronological age.

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

Why are Dolly and the cow clones so different in this respect? The Science authors suggest a number of reasons, including differences in cloning techniques. Rather than creating clones from cells at the end of their lifespan, as was the case with the cows, Dolly's creators used cells that had been starved and sent into a resting state. Differences in the original donor cells used--mammary cells for Dolly and fibroblast (connective tissue) cells for the cows--may also play a role.

"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," says Lanza.

Although the researchers still don't know whether these findings mean that the animals themselves will have longer lifespans, they are continuing their work to discover exactly how the cloning process reprograms the youth back into cells. In the meantime, future possibilities for these cells could include their use in engineering replacement tissues for humans. "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. This could have profound ramifications for alleviating our current organ donor shortage," notes Lanza.