Diacetyl odor shortens longevity conferred by food deprivation in C. elegans via downregulation of DAF-16/FOXO.

Dietary restriction extends lifespan in various organisms by reducing the levels of both nutrients and non-nutritional food-derived cues. However, the identity of specific food-derived chemical cues that alter lifespan remains unclear. Here, we identified several volatile attractants that decreased the longevity on food deprivation, a dietary restriction regimen in Caenorhabditis elegans. In particular, we found that the odor of diacetyl decreased the activity of DAF-16/FOXO, a life-extending transcription factor acting downstream of insulin/IGF-1 signaling. We then demonstrated that the odor of lactic acid bacteria, which produce diacetyl, reduced the nuclear accumulation of DAF-16/FOXO. Unexpectedly, we showed that the odor of diacetyl decreased longevity independently of two established diacetyl receptors, ODR-10 and SRI-14, in sensory neurons. Thus, diacetyl, a food-derived odorant, may shorten food deprivation-induced longevity via decreasing the activity of DAF-16/FOXO through binding to unidentified receptors.