The influence of diet on lifespan has been an enduring theme in biological studies of ageing, many of which have indicated that simply reducing food intake can lead to longer life. However, there is clearly more to longevity than starvation. In the nematode C. elegans, there seem to be at least two genetic pathways affecting lifespan. Lakowski and Hekimi 1 Lakowski B. Hekimi S. (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13091-13096 Crossref PubMed Scopus (704) Google Scholar have examined the effect of caloric restriction by following the lives of ‘eat’ mutants, which have pharyngeal defects and therefore feed at a lower rate than normal worms. Most of these semi-starved mutants do indeed live longer than wild type, with six of nine genes tested showing increased longevity, up to 47% in the case of an eat-2 mutant. The starvation effect impinges on the same pathway as the clk-1 gene, previously shown to affect ageing, because eat-2; clk-1 double mutants live no longer than either single mutant. However, a different double mutant, eat-2; daf-2, exhibits an additive increase in lifespan, suggesting that daf-2 affects ageing by a different mechanism. The daf-2 gene encodes a protein related to vertebrate insulin receptors, and forms part of a regulatory cascade affecting both diapause (dauer larva formation) and lifespan. Apfeld and Kenyon 2 Apfeld J. Kenyon C. Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and lifespan. Cell. 1998; 95: 199-210 Abstract Full Text Full Text PDF PubMed Scopus (267) Google Scholar have asked what are the critical tissues in which daf-2 must act in order to regulate these processes, by examining animals that are genetically mosaic for daf-2. Remarkably, they find that daf-2 acts non-autonomously, so that both entry into diapause and lifespan can be influenced in a systemic way. In the extreme cases, some of the mosaic animals possess only a few mutant neurons in an otherwise wild-type body, yet all their tissues adopt the dauer state. At least six non-overlapping sets of cells can have this effect, but not invariably, indicating partially redundant action. Similar non-autonomous effects were seen in parallel studies of the long-life phenotype. These results suggest the existence of a diffusible signal, identity so far unknown, which can act to regulate the ageing of cells throughout the animal and therefore could almost be seen as an elixir of life... but maybe only for worms.