Integrating Transcriptomics and Free Fatty Acid Profiling Analysis Reveal Cu Induces Shortened Lifespan and Increased...

Nowadays, human beings are exposed to Cu in varieties of environmental mediums, resulting in health risks needing urgent attention. Our research found that Cu shortened lifespan and induced aging-related phenotypes of Caenorhabditis elegans (C. elegans). Transcriptomics data showed differential expression genes induced by Cu were mainly involved in regulation of metabolism and longevity, especially in fatty acid metabolism. Quantitative detection of free fatty acid by GC/MS further found that Cu upregulated free fatty acids of C. elegans. A mechanism study confirmed that Cu promoted the fat accumulation in nematodes, which was owing to disorder of fatty acid desaturase and CoA synthetase, endoplasmic reticulum unfolded protein response (UPR^ER), mitochondrial membrane potential, and unfolded protein response (UPR^mt). In addition, Cu activated oxidative stress and prevented DAF-16 translocating into nuclear with a concomitant reduction in the expression of environmental stress-related genes. Taken together, the research suggested that Cu promoted aging and induced fat deposition and oxidative damage.