Secrets behind ageing provide clues for controlling cancer

Cancer Research UK

Scientists have uncovered important clues about how cells age - a discovery that could help counteract cancer's ability to grow and spread.

A report published on-line in the journal Nature1 reveals the molecular events that take place when a cell becomes old and stops dividing.

Scientists from Cancer Research UK, The Wellcome Trust, and The Institute of Ageing and Health at the University of Newcastle upon Tyne have found a key mechanism for repairing damaged DNA can also stop ageing cells from dividing by sending them into a permanent state of slumber.

They believe understanding what happens when cells grow old will lead to new ways to age cancer cells and halt their rapid growth and division. Their findings may also help identify the start of cellular ageing and provide a method for diagnosing cancer at an early stage.

Normal cells only divide a certain number of times before they become old and fall asleep, or senesce. But this process goes wrong in cancer cells and they continue to multiply well beyond their allotted lifespan.

Cancer Research UK's Professor Steve Jackson, lead researcher on the study at the Wellcome Trust/Cancer Research UK Institute in Cambridge, says: "Healthy cells automatically enter a permanent resting state when they get old where they are still alive but can no longer divide. Cancer cells, however, are faulty and find ways around this natural ageing process, so that they can continue to grow and divide."

"If we can work out how healthy cells put themselves to sleep we can try and restore this process in cancer cells."

When cells age, structures called telomeres are worn away from the ends of chromosomes - the bundles of DNA that contain our genes. Telomeres protect chromosomes from becoming tangled or degraded, so they can be faithfully copied when cells divide.

As telomeres get shorter they begin to fail and can no longer perform their protective functions.

In the new study, scientists found molecules that repair damaged DNA recognise worn telomeres as genetic damage.

Scientists already knew these molecules activate a response to damaged DNA to repair it and prevent the cell from dividing before this process has taken place.

Now they have found the repair molecules initiate this mechanism when telomeres are worn away - sending the ageing cell to sleep and preventing it from dividing further.

The DNA repair molecules form structures at the end of telomeres, which the scientists have called SDF's (Senescence-associated DNA Damage Foci). They found that SDF's are only present in senescent cells and not young cells.

They also discovered that blocking the response from the DNA repair molecules could cause senescent cells to wake-up and begin dividing again - proving the mechanism was responsible for telling the cell it is time to sleep and stop dividing.

Prof Jackson says: "While we are not yet able to fully reverse the process of cell ageing our study gives us an insight into what happens when a cell grows old. This has important implications for age-related-disorders and cancer - a disease in which cells are able to avoid ageing.

"Now we know how healthy cells age, we can work out how cancer cells ignore this process, which could lead to new treatments for the disease."

He adds: "Since we have found a structure that is only present in senescent cells, we have a diagnostic marker for cell ageing, which could allow us to distinguish between healthy cells and cancer cells. This may help us detect cancer at a very early stage."

Professor Alex Markham, Chief Executive of Cancer Research UK, says: "This is a very interesting finding which provides us with important clues on how the ageing process might be triggered in cancer cells and could lead to new ways of tackling the disease."

ENDS

  1. Nature426 pp.194-198.

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