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 Wednesday, 28 July, 1999, 08:17 GMT 09:17 UK
'Ageing molecule' secrets revealed
Telomeres protect the ends of chromosomes
Mice that went prematurely grey, got cancer more often and died early have given scientists an intriguing insight in live animals of the ageing process.

The rodents also lost their hair more quickly and took longer to recover from the stress of surgery and chemotherapy than normal mice.

The mice were bred without a gene for making telomerase. This enzyme builds and maintains telomeres - nubs of protein that scientists believe may be central in controlling the ageing process.

Telomeres are produced during embryonic development but start to crumble away as cells mature and divide. Until now, this process had only been studied in cells cultured in the lab.

The mice were bred at the Dana-Farber Cancer Institute (DFCI) in Boston. Each rodent generation bred by the DFCI team had progressively shorter telomeres.

Ageing problems

The problems associated with ageing were not immediately apparent in the new-born mice. For example, third generation mice displayed symptoms only after they had reached the age of 18 months. Even the most telomere-deficient, sixth-generation mice had to go through a waiting period, albeit shorter, before symptoms appeared.

This surprised the team. Although the mouse findings confirm expectations about telomere shortening and its role in ageing, they also show the process to be far more complex than previously thought.

"Something else in the ageing organism co-operates with telomere dysfunction to compromise fitness," says Lenhard Rudolph, research associate in medicine at DFCI and Harvard Medical School (HMS), and lead author of the study.

"What else that is remains unclear. That's one of the central questions in biology - what is the basis for organismal ageing? Is it free radical damage that accumulates? Is it general mitochondrial dysfunction? Or are there other mechanisms?"

The higher number of tumours in the mice is also a conundrum. The experiments demonstrate the widely held belief that telomeres are associated with cancer - but, again, in a more complex way.

Cancer cells

From previous work, it is clear that cells can become cancerous because too much telomerase makes them "immortal". But this new research shows a lack of telomerase can also lead to cancer.

"These experiments have been to a certain extent mind-bending. No-one would have anticipated that you could have gotten an increase in cancer from a lack of telomerase," says Ron DePinho, also at DFCI.

As a possible explanation, the team suggest that DNA strands that lose the protection of their telomeres might fuse or break. This could lead to the loss or gain of genes and, in turn, to cancer.

Telomerase is the subject of intense investigation in several labs. Not only does it provide a target for anti-cancer drugs but it plays an important role in embryonic stem cells which many scientists hope will one day provide spare tissue and even organs for transplantation.

The media has also followed the telomerase story closely, not least because some scientists have suggested that control of the enzyme may enable us to live longer lives.

This latest research is published in the journal Cell.

See also:

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