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.