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A new Frontiers in Aging study provides insights into the novel mechanisms through which blue light (BL) exposure interferes with non-retinal cell metabolic pathways in flies. These findings indicate that BL exposure likely imposes similar effects on human cells, such as those of the skin, fat, and other tissues.
Study: Chronic blue light leads to accelerated aging in Drosophila by impairing energy metabolism and neurotransmitter levels. Image Credit: Aleksy Boyko / Shutterstock.com
BL, which is a common component of light-emitting diodes (LED) lights, is a high-energy light with short wavelengths that can cause retinal damage. Previous studies suggest that BL can cause retinal degeneration, age-related maculopathy, and glaucoma; however, the mechanisms responsible for BL-associated phototoxicity remain unclear.
Drosophila melanogaster, which is more commonly referred to as the fruit fly, has also been shown to experience acute BL phototoxicity. Exposure of compound eyes to BL precipitates lipid peroxidation, oxidative stress, and retinal degeneration due to phototransduction. These effects have been reported in wild and mutant flies with ablated eyes (eya2).
The current study aimed to ascertain the effects of chronic BL exposure on the metabolic pathways within the extra-retinal tissues of eya2.
Herein, flies were kept in complete darkness or constant BL exposure for 10 or 14 days. Metabolite profiles of the cells were assessed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS).
Constant BL exposure significantly reduced the longevity of eya2. Further investigation revealed a more significant decrease in longevity of flies exposed to BL for 14 days as compared to those following 10 days of BL exposure.
No death was recorded at either of these time points. However, some flies that remained under constant BL exposure died after 16 days, whereas others survived in constant darkness (DD). This observation implies that the flies may sustain either irreversible or reversible damage due to constant BL exposure.
The researchers subsequently assessed neurodegeneration in male mutant flies exposed to BL for 10, 14, or 16 days and compared these results with DD controls at the same time points. To this end, constant exposure to BL for 10 days had similarly negligible vacuolization to that which was observed in DD controls. However, after 14 days, significant vacuolization in the brain was observed in BL-exposed flies as compared to DD controls at this time point.
Further investigation of the metabolomic profiles of male eya2 after constant exposure to BL at 10 and 14 days using LC-MS and GC-MS was conducted. LC-MS of BL-exposed flies for 10 days identified 175 metabolites, nine significantly altered compared to DD controls.
Principal component analysis (PCA) revealed a weak separation and minimum coverage rate. Furthermore, the levels of most metabolites were reduced after constant exposure to BL.
LC-MS of BL-exposed flies for 14 days led to the identification of 176 metabolites, 30 of which were significantly altered as compared to DD controls. This indicates more significant metabolic changes were induced when the duration of BL exposure increased.
Out of the 30 metabolites, 21 were down-regulated and nine were up-regulated. Except for uridine diphosphate glucose (UPD-glucose), hydroxypropionate, and 3-ureidopropanoate, most of the metabolites that were altered after 10 days of constant BL exposure remained significantly altered after 14 days. Riboflavin and succinate levels exhibited the most significant reductions and increases, respectively, of all metabolites.
GC-MS of BL-exposed flies for 14 days detected a total of 87 metabolites, 10 of which were altered significantly. Constant exposure to BL also reduced metabolite levels.
Overall, five downregulated and five upregulated metabolites were detected. There were significant differences in beta-alanine, glycerol 3-phosphate (G3P), and succinate concentrations. Significant alterations were also detected in 3-aminoisobutanoic acid, threonine, citrate, isoleucine, and homoserine metabolites.
Both, LC-MS and GC-MS on flies with constant BL exposure revealed succinate to be one of the most significantly increased metabolites, thereby suggesting compromised activity of the enzyme succinate dehydrogenase (SDH). When SDH activity was assessed in both DD control and BL-exposed flies for 10 and 14 days, a significant reduction in SDH activity after BL exposure was observed at both time points. Thus, SDH levels can be used to determine ay metabolic impairment.
Alanine, aspartate, and glutamate (AAG) metabolism, as well as tricarboxylic acid cycle (TCA), butanoate metabolism, and riboflavin metabolism, were the most severely altered pathways following BL exposure. BL exposure also significantly reduced the levels of many non-essential amino acids like aspartate, glutamate, asparagine alanine, and arginosuccinate.
TCA cycle metabolites like acetoacetate, citrate and glucose-derived pyruvate were significantly reduced after constant BL exposure, thus implying severe impairments in energy production after BL exposure.
BL exposure also led to a significant increase in adenine diphosphate (ADP) levels. Conversely, adenine triphosphate (ATP) levels were reduced following 14 days of constant BL exposure to a greater extent as compared to the reduction observed following 10 days of BL exposure. Both ATP reductions were in reference to that of the DD control flies.
Significant neurodegeneration was also observed in flies after a BL exposure of 14 days. More specifically, significant reductions in inhibitory gamma-aminobutyric acid (GABA), excitatory glutamate, histamine, and alanine levels were observed.
No significant difference between dopamine and acetylcholine levels in DD control flies and those exposed to BL was observed. However, serotonin levels were moderately raised in BL-exposed flies. These findings suggest an imbalance in neurotransmitters in the mutant eyeless D. melanogaster.
Glutamate, which has an important role in metabolic homeostasis, was also deficient in BL-exposed flies. To confirm the role of glutamate deficiency in accelerating the aging of flies exposed to BL, the diet of the flies was supplemented with 200 and 400 micrograms (µg)/ml of glutamate.
A 200 µg/ml dose of glutamate did not significantly impact the lifespan of BL-exposed flies. Comparatively, 400 µg/ml supplementation shortened the lifespan of flies as compared to controls not supplemented with glutamate.
Riboflavin, which is otherwise known as vitamin B2, was the most significantly diminished metabolite after constant BL exposure. The effects of riboflavin supplementation on mutant flies after chronic BL exposure were tested. To this end, both 200 and 400 µg/ml of riboflavin shortened the lifespan of flies as compared to controls that were not supplemented.
The current study provides novel insights into the mechanisms by which BL affects vital metabolic pathways and specific processes in Drosophila melanogaster, specifically in cells that are not specialized in phototransduction.