Abstract Background: Despite recent progress in understanding the molecular mechanisms regulating aging and lifespan, and the pathways involved being conserved in diferent species, a full understanding of the aging process has not been reached. In particular, increasing evidence suggests an active role for the nervous system in lifespan regulation, with sensory neurons, as well as serotonin and GABA signaling, having been shown to regulate lifespan in Caenorhab ditis elegans (C. elegans). However, the contribution of additional neural factors, and a broad understanding of the role of the nervous system in regulating aging remains to be established. Here, we examine the impact of the dopamine system in regulating aging in C. elegans. Results: We report that mutations of DOP-4, a dopamine D1-like receptor (D1R), and DOP-2, a dopamine D2-like receptor (D2R) oppositely afected lifespan, fast body movement span, reproductive lifespan, and developmental rate in C. elegans. Activation of D2R using aripiprazole, an antipsychotic drug, robustly extended both lifespan and health‑ span. Conversely, inhibition of D2R using quetiapine shortened worm lifespan, further supporting the role of dopa‑ mine receptors in lifespan regulation. Mechanistically, D2R signaling regulates lifespan through a dietary restriction mechanism mediated by the AAK-2-DAF-16 pathway. The DAG-PKC/PKD pathway links signaling between dopamine receptors and the downstream AAK-2-DAF-16 pathway to transmit longevity signals. Conclusions: These data demonstrated a novel role of dopamine receptors in lifespan and dietary restriction regula‑ tion. The clinically approved antipsychotic aripiprazole holds potential as a novel anti-aging drug.