Chlorophyll Supplementation Delays Aging in <i>Drosophila melanogaster</i> via Enhanced Stress Resistance and Detoxification Network Remodeling.

<h4>Background</h4>Chlorophyll (Chl), widespread in fruits and vegetables, has been shown to have numerous nutritional functions, including beneficial effects on obesity. However, whether Chl has an anti-aging effect remains unclear.<h4>Methods</h4>Here, we studied the beneficial effects and mechanism of Chl on delaying aging using a <i>Drosophila</i> model.<h4>Results</h4>The results showed that dietary supplementation of Chl in an appropriate dose (3.925 mg/L) significantly extended the lifespan (7.66-13.94%), improved climbing ability, increased CAT activity, reduced MDA content, enhanced stress resistance to starvation, heat stress, and cold shock in <i>Drosophila</i>. Notably, lifespan extension was not associated with dietary restriction, reproductive sacrifice, or circadian rhythm regulation. RNA-Seq analysis showed that Chl supplementation led to differential expression of 723 genes in female flies and 435 genes in male flies. KEGG analysis revealed that these differentially expressed genes were significantly enriched in the xenobiotic metabolism (XM) pathway. Within this pathway, phase II detoxifying enzyme genes associated with the CncC (Nrf2) signaling pathway (<i>GstD10</i>, <i>GstE7</i>, <i>Ugt37A3</i>, and <i>AOX2</i>) were significantly downregulated in both sexes. In contrast, protective target genes from the same pathway (<i>cat</i>, <i>Mrp4</i>, <i>Hsp68</i>) were significantly upregulated, as confirmed by qPCR.<h4>Conclusions</h4>Taken together, our data indicate that Chl supplementation delays aging in <i>Drosophila melanogaster</i> via enhanced stress resistance and remodeling of the detoxification network.