The mushroom body (MB) is the regulatory center of several brain functions including learning, memory, and sleep in Drosophila. Whether MB regulates lifespan has not been investigated. MB is composed of Kenyon cells, calyces and five distinct lobes including the vertical α, α', medial β, β', and γ lobes. Further functional analysis subdivides the αβ neurons into at least 3 subsets: αβ pioneer (αβp), αβ surface (αβs), and αβ core (αβc). Here, we show that Rab27 controls lifespan in the αβp neurons of MB. Rab27 is an evolutionarily conserved Rab GTPase mediating the exocytic machinery in neuroendocrine cells. We characterized the rab27 knockout (KO) flies, and no obvious developmental defect was observed, except that loss of rab27 significantly extended lifespan. Specifically, rab27 knockdown in the αβp neurons promoted longevity. To reveal the signal transduction, we first examined the insulin/IGF signaling (IIS) pathway. rab27 knockdown in the median neurosecretory cells (mNSCs) by dilp2-Gal4 did not extend lifespan and suppression of IIS in rab27KO background further extended lifespan. Moreover, the level of phosphorylation of AKT (pAKT), a downstream component of IIS, was not decreased in rab27KO brains. Thus the longevity phenotype was not due to reduced IIS. Rather, reduction of rab27 leads to decreased phosphorylation of S6 (pS6), a downstream component of target of rapamycin (TOR) signaling. Consistently, suppression of TOR signaling by feeding rapamycin or expressing either TSC2 or S6KDN does not further increase the longevity of rab27KO, indicating that Rab27 functions through TOR signaling but not IIS pathway. We propose that reduction of rab27 attenuates TOR signaling at the level of pS6. Further molecular evidence will be presented. Taken together, the results pinpointed αβp neurons of MB as an important region to control longevity. We discovered a novel site of TOR function in a specific neuronal circuitry for lifespan extension.