Cloned cows suggest aging of cells can be reversed

By LAURAN NEERGAARD, Associated Press

WASHINGTON (April 27, 2000 3:06 p.m. EDT http://www.nandotimes.com) - Massachusetts scientists have cloned six cows that show none of the worrisome premature aging reported for Dolly the sheep. In fact, the cows' cells seem to have a surprisingly prolonged youth, a new study shows.

The finding is important because it could erase doubts about trying to use cloned cells to fight diseases, doubts raised when scientists discovered Dolly's cells appeared older than she was.

But the cloned cows - the oldest turned a year old this week, while the others are 7 months old - have cells that appear as young as the cells of newborn calves, researchers with the biotechnology company Advanced Cell Technologies report in Friday's edition of the journal Science.

Unlike Dolly, the cows were cloned from cells nearing the end of their lifespan. If even very old cells can have their "aging clock" essentially rewound, then scientists might one day be able to clone customized replacement tissues for patients suffering diabetes, Parkinson's or other diseases, say experts on cellular aging.

Does it also mean the cloned cows could live longer than normal? Maybe, says Advanced Cell Technologies' chief scientist, Dr. Robert Lanza. "There's a chance these could be the longest-lived cows on the planet."

But no one will know that for years, cautioned Thoru Pederson, a cellular biologist at the University of Massachusetts Medical School. After all, cows typically live 20 years, and there's more to aging than the cellular characteristic the company is investigating.

"It's important not to over-dramatize this as a 'fountain of youth' thing," stressed one of the nation's leading experts on cellular aging, Jerry Shay of the University of Texas Southwestern Medical Center.

Instead, Shay says, the study provides "the first very dramatic proof" that people's very old cells could one day be rejuvenated for tissue engineering.

Cells can divide only a certain number of times before they die - about 70 times for human cells; around 60 times for cows.

All chromosomes have protective tips called telomeres that prevent a cell's genetic code from fraying during this cellular division. But each time the cell divides, the telomere gets a little shorter. It eventually becomes too short to protect the chromosome, so the cell can no longer divide and eventually dies.

Dolly was the first large animal to be cloned from genetic material extracted from an adult cell. She seems healthy. But last year, scientists discovered her telomeres were too short - while she was just 3, her genetic material was aging at the rate of the 6-year-old sheep from which she was cloned. Not only did that suggest Dolly could age and sicken prematurely, it meant any cloned cells one day developed as medical treatments might be too old to last in the body and fight disease.

Now Advanced Cell Technologies has discovered the opposite effect: Its six new cloned cows have telomeres significantly longer than regular cows the same age - in other words, the cells look far younger than expected.

When cloned cow cells were put in a lab dish, they divided more than 90 times before dying, the researchers report in Science.

And the company just had four new calves born last month that had telomeres "longer than any I've ever seen," Lanza added.

Why? Nobody knows.

The cow cloning process is done a little differently than Dolly was cloned. The sheep was cloned from a cell that temporarily stopped dividing, not a terribly old cell. In contrast, Lanza let cow cells divide in a dish for several months until they were at the very end of their lifespan, a period called senescence. He cloned only the oldest of these old cells, ones with incredibly short telomeres.

One theory: Putting super-old genetic material into an egg - the next step in cloning - may prompt the egg to overreact and ensure it produces an embryo with extra-long telomeres, Shay said.

"This is good news," said Huber Warner, associate director of the National Institute on Aging. "This says telomeres can be repaired."