Polyphenol extracts from rambutan peel promote longevity <i>via</i> the attenuation of the Toll/Imd pathway

Rambutan peel is rich in polyphenols such as ellagic acid, corilagin, geraniin, quercetin, and rutin, which contribute to its diverse health benefits, including antioxidant, antimicrobial, antiviral, anti-inflammatory, hypoglycemic, and potential anticancer properties. The polyphenols present in the rambutan peel demonstrate potential for delaying cellular aging by mitigating oxidative stress within cells. Moreover, no study has systematically explored the anti-aging effects and the underlying mechanisms of polyphenols derived from rambutan peel. <i>Drosophila melanogaster</i> has often been used in aging studies to reveal the mechanisms of aging onset and development. Using <i>Drosophila melanogaster</i> as an <i>in vivo</i> aging model, the aim of the present study was to probe whether rambutan peel polyphenol extracts (RPPEs) exert a lifespan extending effect <i>in vivo</i> and to gain insights into the mechanism of action. Results highlighted that the optimized concentration of RPPEs for the anti-aging treatment in <i>Drosophila melanogaster</i> was 5 mg mL^-1. In addition, RPPEs extended the lifespan of <i>Drosophila melanogaster</i> in a manner that was related to the dose and gender. Meanwhile, RPPEs improved the climbing ability and sleep and maintained the antioxidant capacity of aged <i>Drosophila</i>. RPPEs also ameliorated intestinal barrier damage in aging <i>Drosophila</i>. Transcriptome sequencing analysis showed that RPPEs extended the lifespan of <i>Drosophila</i> by down-regulating the Toll/IMD signaling pathway.