| Summary: | Aspirin and curcumin have been reported to be beneficial to anti-aging in a variety of biological models. Here, we synthesized a novel compound, curcumin acetylsalicylate (CA), by combining aspirin and curcumin. We characterized how CA affects the lifespan of <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) worms. Our results demonstrated that CA extended the lifespan of worms in a dose-dependent manner and reached its highest anti-aging effect at the concentration of 20 μM. In addition, CA reduced the deposition of lipofuscin or “age pigment” without affecting the reproductivity of worms. CA also caused a rightward shift of <i>C. elegans</i> lifespan curves in the presence of paraquat-induced (5 mM) oxidative stress or 37 °C acute heat shock. Additionally, CA treatment decreased the reactive oxygen species (ROS) level in <i>C. elegans</i> and increased the expression of downstream genes superoxide dismutase <i>(sod)-3</i>, glutathione S-transferase <i>(gst)-4</i>, heat shock protein <i>(hsp)-16.2,</i> and catalase-1 <i>(ctl-1)</i>. Notably, CA treatment resulted in nuclear translocation of the DAF-16 transcription factor, which is known to stimulate the expression of SOD-3, GST-4, HSP-16, and CTL-1. CA did not produce a longevity effect in <i>daf-16</i> mutants. In sum, our data indicate that CA delayed the aging of <i>C. elegans</i> without affecting reproductivity, and this effect may be mediated by its activation of DAF-16 and subsequent expression of antioxidative genes, such as <i>sod-3</i> and <i>gst-4</i>. Our study suggests that novel anti-aging drugs may be developed by combining two individual drugs.
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