Ageing clues from clones of clones

Researchers have cloned six successive generations of mice in an experiment that gives new insights into ageing.

The sequentially cloned mice showed no signs of growing old prematurely and appeared mentally and physically normal.

However, the experiment came to a sudden end when the single, sixth-generation mouse clone was eaten by her foster mother.

And the difficulty of cloning the mice increased for each new generation with an overall success rate of only 1-2%.

Protective structures

To create the clones, the researchers, led by Professor Teruhiko Wakayama of Rockefeller University, New York, transferred genetic material from the nuclei of adult female mice into empty mouse eggs.

This technique, known as nuclear transfer, has been used to clone a number of animals including sheep, goats, mice and cows.

But questions remain about whether cloning leads to adverse health effects, such as premature ageing.

To try to clarify the issue, scientists have been studying telomeres - protective structures at the ends of chromosomes - which they believe may play a central role in the ageing processes of cells.

Each generation

Dolly the Sheep was found to have shorter telomeres than expected for her age, which prompted suggestions that she might not live long or be at higher risk of developing diseases associated with old age.

Dolly's telomeres were shorter than expected

But studies of other animal clones have found longer telomeres than normal, suggesting cloning might even reverse the ageing process.

These experiments involved only a single round of cloning. So the researchers studied clones of clones to find out what happened to their telomeres.

Reporting their findings in the journal Nature, the American-based team said they were surprised to find that the telomeres of the cloned mice appeared to lengthen slightly with each generation.

Cloning defects

"Any deleterious effects of cloning might be expected to be amplified in sequentially cloned mice," said Wakayama's group. "Our results verify that telomere shortening is not a necessary outcome of the cloning process."

But the researchers admitted that, since only 1 to 2% of cloning attempts were successful, they could not rule out the possibility that the cloning process selected for cells with unusually long telomeres.

Dr Harry Griffin from the Roslin Institute, UK, where Dolly was produced, shares this view.

"Cloning is very unsuccessful," he told BBC News Online. "The efficiencies are low and it may be that there is a selection for cells that have longer or shorter telomeres than normal."

Other factors, such as the type of tissue or the species of animal used for cloning experiments might also be important, he said.

"I don't think that shortened telomeres in Dolly had any consequence for her lifespan," Dr Griffin added. "She's still fine."