Dr Alexander Bürkle - a scientist working with Tom Kirkwood's team at the Institute of Ageing and Health in Newcastle. Dr Bürkle is researching a protein called PARP-1, and its function in repairing DNA damage and preventing ageing and cancer in cells.

Could you explain how oxidising damages DNA, affecting the ageing process and the process of cancer formation?
Oxygen is an extremely important molecule for normal cells to work and to survive. Unfortunately, oxygen has also the ability to transform into aggressive molecules called oxygen free radicals, special kinds of oxygen atoms which have the ability to create molecular damage, so they can interfere with the structure and function of biological molecules such as proteins, RNA and DNA. DNA is quite special in this regard, because it is the only way a cell can in the long term store biological information and it is present in a low number of copies in each cell, therefore it is very important that cells maintain their DNA in a perfect or almost perfect state of integrity. Oxiditive damage of DNA means that subtle changes in the structure and in the coding capacity of DNA is introduced, and this molecular damage can lead to mutation of the genetic code, or else it can lead to the situation that genes - specific parts of the DNA - can no longer be transcribed and translated.

This explains the intimate relationship between normal ageing and the process of cancer formation. It is well-known that most types of cancers are age-related diseases, and so researchers have speculated a long time ago that there may be common roots for both phenomena. And actually DNA damage as it is induced by oxidants or by other DNA-damaging compounds, seems to be the driving force of both processes - cancer formation and the ageing process at large. Therefore we firmly believe that if we unravel and understand the molecular mechanisms leading to DNA damage and its repair we will get a good understanding both of the ageing process and of the process of carcenogenesis.

What results have you got so far from your research into DNA damage?
The gene we are particularly focussing on in my research group is called Parp 1 and this gene encodes a protein which is one of the tools the cell has in its toolbox to fix and repair genetic damage. Parp1 seems to be the sensor of DNA damage, oxiditive DNA damage for instance, and so we are extremely interested in learning what the role and the function of Parp 1 is, both in the process of ageing and in the process of carcenogenesis. Research started some years ago found that the longer lived an animal species was, the more proficient this repair tool turned out to be in blood cells we had studied. Very recently we found that Parp 1 is actually a key regulator and modulator of genomic stability. This is a significant discovery because if there's too much genomic instability going on the cell can either die because it will end up in a totally dysfunctional or non-functional state, or else it can be transformed into a malignant tumour cell that has fully maintained the capacity to grow, but has completely escaped any control of its growth.

How can diet affect cell damage and therefore the ageing process?
Ageing is clearly a multi-factorial phenomenon, it is controlled both by genetic factors and environmental factors. An important environmental factor is, of course, diet which can modulate the ageing process by contributing beneficial factors, factors that would help maintain and repair any damage that occurred in cells, such as vitamins, which the body cannot synthesise itself, but which the body needs to take up in the diet. It can also contain damaging factors that add to the problem rather, so, for example, if you have an unhealthy diet that is rich is sugar and saturated fat, it is known that this can increase the burden of cells with regards to oxiditive damage.

How is your research beneficial in terms of old people's health?
We hope very much that the work we are doing in basic biogerentology - that is to understand basic molecular mechanisms operating in every cell that lead to the process of ageing - will contribute to an improved quality of life for the elderly. We assume that many ageing associated diseases, like cardiovascular disease, Alzheimer's disease, cancer and many others, result from deficiencies, perhaps just subtle deficiencies, in the body maintenance and repair functions. Therefore, if we manage to understand these maintenance and repair functions, if we can detect early on any deficiency in such functions, perhaps in specific organs, then we have a chance for intervention to correct the deficiency if possible, so allowing the individual to live to his or her full potential life span.

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Content last updated: 17/07/2006

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