The aim of this study was to uncover the molecular mechanism for high-sugar diet-induced aging of Caenorhabditis elegans. Changes in the gene expression profile of C. elegans induced by a high-glucose (HG) diet were explored by transcriptomics. The results showed that the expression of 4183 genes in C. elegans significantly changed after HG diet consumption. In addition, Gene Ontology (GO) enrichment analysis showed that differentially expressed genes (DEGs) induced by HG diet treatment were significantly enriched in aging, unfolded protein binding, response to stress, autophagy, transferase activity, catalytic activity, and heat shock protein binding. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DEGs were also significantly enriched in longevity regulation of C. elegans, autophagy regulation, pyruvate metabolism, the forkhead box O (FOXO) signaling pathway, glycolysis/gluconeogenesis, glutathione metabolism, and the transforming growth factor-β signaling pathway. Furthermore, we found that high-glucose diet up-regulated the expression of DEGs involved in the insulin/IGF-1 signaling (IIS) pathway and of DEGs associated with glycolipid metabolism, and down-regulated the expression of DEGs related to heat stress resistance and antioxidant regulation. This study provides a theoretical basis for further elucidation of the molecular mechanism underlying the effects of HG diet on the longevity and metabolism of C. elegans.
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