Madrid brings me face to face with matters of mortality. Maria Blasco (Spanish National Cancer Institute) talks to me about tumours, telomeres and telomerase. Her research team are interested in the ends of our chromosomes, which play a role in determining the lifespan of our cells, and thereby our bodies. Telomeres are found at chromosomal ends. In humans the sequence TTAGGG is replicated over a thousand-fold and every time a cell divides and makes new chromosomes, telomeres get shorter. “When the telomeres get really short the cells stop dividing,” explains Maria. When this happens, the enzyme telomerase kicks in to rebuild the telomere.

Paradoxically mice seem to have telomeres four times the length of that in humans. Maria’s team have created a mouse model that cannot make telomerase, which gives them shorter telomeres, more like those in humans. “The critical length for telomeres is not clear, in terms of the exact number of repeats,” she affirms, “We think that the critical length is related to the ability of chromosomes to form a protective structure. When the length of a telomere goes below 100 repeats or so, this is associated with loss of telomere protection.” Maria’s mice have intrigued her Spanish research team because they get fewer tumours than normal.

She clarifies the significance of this observation. “Telomerase gets activated in 90% of human tumours. So when you make telomeres really short in mice this acts as a tumour suppressor mechanism.” As we get older our telomeres shorten naturally, but in cancer cells, which have divided many more times than normal, telomeres are much shorter, and they rely on the telomerase enzyme. “Very high levels of telomerase make the tumour immortal,” says Maria.

“Normal cells don’t have telomerase activity. So if you inhibit telomerase, it’s already specific for tumour cells.” So what does this have to do with epigenetics? Maria is currently investigating the nature of chromatin at telomeres. The biochemical status of histone proteins at telomeric DNA seems to keep the ends safe from the action of enzymes that could either build or break them. The results of such research will no doubt be crucial to any anti-cancer initiatives focussed on blocking telomerase activity.