Bacterial Nitric Oxide Extends the Lifespan of C. elegans

Nitric oxide (NO) is an important signaling molecule in multicellular organisms. Most animals produce NO from L-arginine via a family of dedicated enzymes known as NO synthases (NOSes). A rare exception is the roundworm Caenorhabditis elegans, which lacks its own NOS. However, in its natural environment, C. elegans feeds on Bacilli that possess functional NOS. Here, we demonstrate that bacterially derived NO enhances C. elegans longevity and stress resistance via a defined group of genes that function under the dual control of HSF-1 and DAF-16 transcription factors. Our work provides an example of interspecies signaling by a small molecule and illustrates the lifelong value of commensal bacteria to their host. [Display omitted] ► NO produced by gut bacteria diffuses and acts within C. elegance tissues ► NO increases C. elegans lifespan in a DAF-16- and HSF-1-dependent manner ► NO induces heat shock response and thermotolerance in C. elegans ► Transcriptomic analysis reveals the NO regulon under dual control of DAF-16/HSF-1 Nitric oxide produced by B. subtilis, a part of the natural diet of C. elegans, diffuses into the worm’s tissues and activates genes that modulate stress resistance and longevity via the transcription factors HSF-1 and DAF-16.