Research on replicative damage and ageing

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Damaged DNA plays a vital part in both cancer and ageing. A deeper knowledge of how such damage occurs and how cells try to neutralise it can give rise to new treatments for cancer and to a healthier old age. This is Óscar Fernández-Capetillo’s, Professor of Cancer Therapy at the Department of Medical Biochemistry and Biophysics objective.

Damage to our DNA is responsible for both cancer and ageing. But what causes the damage and what does the body do to neutralise it? This is what Professor Óscar Fernández-Capetillo hopes to find out.

“I’ve been concentrating on replicative damage, which is to say the kind of damage that occurs when DNA copies itself during cell division,” he says.

The cell has a system, a toolbox for finding and fixing such faults. By studying and manipulating these tools, Professor Fernández-Capetillo has added to the knowledge of replicative damage. His research group in Madrid was the first in the world to empirically show that a higher degree of replicative damage speeds up the ageing process. The group discovered that most of the damage originated in the fetal stage, despite symptoms not showing through until much later. Professor Fernández-Capetillo’s work has also produced a drug candidate for cancer that pharmaceutical company Merck is now continuing to develop.

“Since cancer cells are much more active than other cells, they are also more dependent on tools for avoiding replicative damage. The inhibition of these tools therefore compromises the tumour. To this end we have found a substance that we have proved to be toxic to tumours. Clinical studies are now being prepared.”

Meanwhile, Professor Fernández-Capetillo continues to search for other ways to strike at cancer and to research into ageing.

“We recently showed that premature ageing in a mouse model can be offset by increasing the cell’s production of nucleotides, which are the building blocks of DNA,” he says.

Text: Anders Nilsson, first published in "From Cell to Society" 2015. Translation: Neil Betteridge.

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