Posted on Oct 09, 2006, 7 a.m.
By Bill Freeman
The link between cancer and ageing is well established
The link between cancer and ageing is well established — the older animals of many species are also more likely to develop tumours. Cynthia Kenyon and colleagues now extend the link further by showing that mutations that extend lifespan in Caenorhabditis elegans also inhibit tumour growth.
To examine the links between ageing and cancer, the authors studied the interactions between mutations that affect the two processes. Mutations in the C. elegans insulin-receptor gene daf-2 extend lifespan by more than twofold. By contrast, mutations in the gld-1 tumour-suppressor gene cause germ cells to re-enter mitosis, overproliferate and give rise to tumours that kill the animal. When the authors combined the two mutations, however, the lifespan was indistinguishable from that of the daf-2 single mutant — the tumorigenic effect of gld-1 was completely abolished.
How might the lack of insulin signalling prevent tumour development? The authors found that cell division decreased and apoptosis increased in the germ lines of the daf-2; gld-1 double mutant compared with the gld-1 single mutant. Interestingly, daf-2 mutations affected only germline mitosis in the tumour, and not in the normal germ lines of otherwise wild-type individuals. Also, they found that p53 was required for increased apoptosis and that introducing a p53 mutation into the double mutant reduced lifespan. This is in contrast to wild-type animals, in which p53 mutations reduce apoptosis but do not affect lifespan.
Are these effects specific to mutations in the insulin-signalling pathway, or do they occur with other lifespan-increasing mutations? Mutations in genes that affect food uptake and mitochondrial pathways also extend lifespan. Worms with such mutations, unlike daf-2 mutants, were not completely unaffected by the gld-1 mutation; however, the daf-2; gld-1 double mutants lived longer than gld-1 animals. These mutations did not affect apoptosis, but they did still reduce tumour incidence. They might therefore have more indirect downstream effects.
A connection between insulin signalling and tumour growth has also been shown in mammals, and it will be interesting to carry out equivalent experiments in mice. These results also suggest that, in contrast to p53, many mutations will have opposing effects on ageing and cancer.Read Full Story