It is a well-known phenomenon, from C. elegans to lab rat to human, that severe dietary restriction greatly extends life span. Of course,the problem is that even if severe dietary restriction didn't extend life span, it would certainly feel like it, as eating becomes a joyless experience. This is why `big pharma' is trying to identify drugs that interfere in the pathway, so that we can eat as much as we like and still live longer. How does the body sense the reduction in nutrient quality, and what is changed? Downstream elements of the pathway seem to include insulin signalling, but which sense is involved is less clear.
Recent work in C. elegans suggested a possible role for taste in longevity, and so Scott Pletcher and colleagues decided to apply Drosophila genetics to the question, because behavioural analyses of olfaction and feeding are also relatively advanced in D. melanogaster. As this tiny fly naturally feeds on rotting fruit, it finds the volatile odours generated by yeast to be particularly appealing. However,a little of what you fancy can actively do you harm, as we shall see. The authors exposed flies on a severely restricted diet to these strong-smelling,volatile odorants from live yeast, or live yeast itself. Both treatments significantly reduced life span, showing that odorants alone are capable of restricting life span. Are these odorants simply toxic? Apparently not,because flies fed on normal diet are unaffected by the same odorants. So it seems as if at least a part of the life extension caused by dietary restriction is attributable to odorant-mediated perception of restricted nutrient availability.
If this were the case, then genetic blockade of olfaction might be expected to extend life span. In Drosophila, olfaction is mediated by a family of 62 odorant receptors. One of these, Or83b, is broadly expressed and is required for correct targeting of other receptors. Mutants are almost anosmic, meaning that they can't smell. Fully-fed female mutants of Or83b lived over 50% longer than wild-type flies, and males also lived longer, although the difference was less spectacular. This increased life span was `rescued' back to normal when a normal copy of Or83bwas expressed in Or83b mutants, showing that the longevity effect was a direct effect of Or83b mutation. In simple terms, these results would suggest that the smell of rich food restricts life span.
What happens when Or83b mutants are exposed to dietary restriction? In fact, the enhanced longevity effect is maintained even under conditions of severe restriction. This shows that olfaction is not a necessary step for the effect of dietary restriction, although there is obviously some interaction between their sense of smell and the effect of eating less. Presumably the fly has some other means of detecting nutritional quality of food, such as sensing the level of nutrients in the haemolymph, so the olfactory pathway is semi-redundant.
Nonetheless, the depressing message from C. elegans and Drosophila is clear: if you want to live longer, eat much less and don't enjoy it.
