View Program - 63rd Annual Drosophila Research Conference

Blue light (BL) is increasingly present in the human environment since BL-enriched LEDs became one of the most common and inexpensive light sources in our homes and workspaces. Blue light is known to damage retina-related cells but also decrease the lifespan in the nematode, C. elegans. Our recent data showed that daily exposure of fruit fly (Drosophila melanogaster) to 12-h of blue light per day accelerates their aging process and shortens their lifespan. The lifespan of flies kept in constant blue light decreases even more significantly – a quarter of the lifespan for dark control (20 days maximum). To understand the mechanism of blue light damage, we transferred flies kept in constant blue light for 6-, 10-, 14-, and 16-days to a constant-dark environment. Mortality curves suggest the blue light damage could be reversed after 14- but not 16-days of BL- exposure. Next, we measured the gene expression with RNA-seq sampled from heads of 6-, 10-, and 14-day-BL-exposed and age-matched dark control flies. DESeq2 gene expression analysis revealed extensive transcriptome re-programming in response to blue light. Over thousands of genes were significantly altered with several genes strongly upregulated, including transcription factor Xrp1, small heat shock protein l(2)efl and Arc1. Differentially expressed genes were enriched for functional groups such as neuropeptides, immunity, and metabolism. To further study the metabolic processes affected by blue light, we performed metabolomics using LC-MS and GC-MS. We detected 216 metabolites in the heads of 10- and 14-day-BL-exposed and control flies. MetaboAnalyst identified 42 compounds significantly altered by blue light. Pathway analysis showed that blue light most significantly impacted compounds in the tricarboxylic acid cycle (TCA), Riboflavin, Propanoate, and Butanoate metabolism. Levels of 4 metabolites in the TCA were reduced while levels of succinate were significantly increased in blue light. Moreover, we also determined that succinate dehydrogenase (SDH) activity was reduced in BL-exposed flies, which suggests the impairment of the electron transport chain in mitochondria. In addition, riboflavin, the precursor of SDH cofactor FAD, was significantly reduced by blue light. Lastly, ADP levels were significantly increased in BL-exposed flies while ATP was decreased. These results show that TCA and mitochondria are impaired in blue light. Another metabolite significantly reduced in BL-exposed flies is glutamate, which serves as an energy substrate and also functions as an excitatory neurotransmitter, and a precursor for the inhibitory neurotransmitter GABA. Taken together, our data suggest that blue light impairs energy metabolism and interferes with brain functions in flies.

Investigating the mechanism of the pro-aging effects of blue light in Drosophila