Abstract
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 Caenorhabditis elegans (C. elegans) 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 C. elegans 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 C. elegans and increased the expression of downstream genes superoxide dismutase (sod)-3, glutathione S-transferase (gst)-4, heat shock protein (hsp)-16.2, and catalase-1 (ctl-1). 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 daf-16 mutants. In sum, our data indicate that CA delayed the aging of C. elegans without affecting reproductivity, and this effect may be mediated by its activation of DAF-16 and subsequent expression of antioxidative genes, such as sod-3 and gst-4. Our study suggests that novel anti-aging drugs may be developed by combining two individual drugs.
Highlights
Aspirin extends the lifespan of Caenorhabditis elegans (C. elegans) and strengthens their stress resistance through a mechanism involving DAF-16/FOXO, AMPK, and LKB1 [5,6]
Curcumin extends the lifespan of worms by reducing intracellular reactive oxygen species (ROS) and lipofuscin [12] or “age pigment” deposition during aging
We introduced the aspirin group into curcumin and esterified two phenolic hydroxyl groups in its structure to obtain a new drug, curcumin acetylsalicylate (CA, patent application number: CN2012101010942A)
Summary
Our data indicate that CA delayed the aging of C. elegans without affecting reproductivity, and this effect may be mediated by its activation of DAF-16 and subsequent expression of antioxidative genes, such as sod-3 and gst-4. Aspirin extends the lifespan of Caenorhabditis elegans (C. elegans) and strengthens their stress resistance through a mechanism involving DAF-16/FOXO, AMPK, and LKB1 [5,6]. Curcumin extends the lifespan of worms by reducing intracellular reactive oxygen species (ROS) and lipofuscin [12] or “age pigment” deposition during aging. The mechanisms underlying the curcumin anti-aging effect in C. elegans involves its antioxidative properties, which affect the size and the pharyngeal pumping rate, suggesting a mechanism similar to dietary restriction. Curcumin maintains a lifespan prolonging effect in mev and daf-16 mutants [12], suggesting a differential mechanism involved. Low absorption and poor bioavailability of curcumin have largely limited its clinical application
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