ß-adrenergic-like signalling engages CrebB in Drosophila gut to promote female longevity

Adrenergic signalling is heavily implicated in human age-related disease and yet the potential for this neuroendocrine signalling pathway to modulate ageing has received little attention. Here, we use Drosophila melanogaster to test if adrenergic-like signalling can promote longevity by manipulating tyramine (TA) or octopamine (OA), the invertebrate equivalents of adrenergic hormones. Increased neuronal synthesis of TA boosts health and longevity in both sexes, whereas OA is marginally beneficial in males. Orally administered TA or OA extend female or male lifespan, respectively. Increased activation of the ß-adrenergic-like signalling in the gut, by manipulating a ß-adrenergic-like receptor, PKA or CrebB, is sufficient to delay female ageing. Transcriptional profiling reveals that CrebB links the ß-adrenergic pathway to longevity-promoting processes in the gut where its function is required for the beneficial effects of TA feeding in females. Here we show that localised activation of ß-adrenergic signalling has the potential to counter animal ageing.