The discovery of genes that are involved in controlling lifespan has led to speculation that, with a little genetic tweaking, we could all live for decades beyond our designated years. But — as anyone who has ever been told they've won a lottery they didn't enter will tell you — if something seems too good to be true, then it probably is. In a recent study, Nicole Jenkins and colleagues looked at mutations that extend lifespan in Caenorhabditis elegans and revealed the biological cost that comes with increased longevity.

The insulin-like growth factor type-I (IGF-I) signalling pathway has a conserved role in regulating lifespan. It has been suggested that altering components of this pathway might be one way to increase longevity without suffering any adverse consequences, as mice that carry mutations in the gene that encodes the IGF-I receptor (Igfr1) show no noticeable defects in metabolism, fertility or reproduction. However, in these studies mutants are generally reared separately from animals of other genotypes, so they are not subject to the effects of natural selection that would apply in natural surroundings.

To take natural selection into account, Jenkins and colleagues studied the fate of a C. elegans line with mutations in the Igfr1 orthologue, daf-2, that was cultured alongside wild-type worms. Similar to their mouse counterparts, daf-2 mutants show normal growth and fertility when reared in isolation. By contrast, in mixed populations, the daf-2 mutation became extinct in just four generations, indicating a strong effect on fitness.

This seems to be at least partly due to effects on fertility. daf-2 mutants produced an average of 22.5 eggs in the same time that wild-type worms produced 50. Applying these numbers to a fitness model predicted that daf-2 mutants would become extinct within seven generations. So, although other fitness effects might also contribute to the even shorter time to extinction seen in the experiments, decreased fertility seems to have an important role.

This fits in with evolutionary models which suggest that increased longevity is selected against owing to adverse effects on reproductive fitness earlier in life. Given the conserved nature of the IGF-I pathway, it seems likely that this will apply to other species as well, reinforcing the need to learn more about the factors that determine lifespan before we can even consider manipulating our own.