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Coenzyme Q10 (CoQ10) is synthesized in almost all human tissues and presumably involved in age-related alterations and diseases. Here, we examined the impact of aging and sex on the serum CoQ10 status in 860 European adults ranging in age from 18 to 82 years. We identified an inverse U-shaped relationship between CoQ10 concentration and age. Women showed lower cholesterol-adjusted CoQ10 levels than men, irrespective of age. As observed in both sexes, the decrease in CoQ10 concentration in older subjects was accompanied by a shift in the redox status in favour of the oxidized form. A strong positive correlation was found for total CoQ10 and cholesterol concentrations (Spearman’s, p≤1E-74). We found strong negative correlations between total (Spearman’s, p≤1E-07) and between cholesterol-adjusted CoQ10 concentration (Spearman’s, p≤1E-14) and the proportion of the oxidized form of CoQ10. These correlations were not dependent on age and sex and were attenuated by supplementation with 150 mg/day reduced CoQ10 for 14 days. Overall, our results are useful to define risk groups with critical CoQ10 status in humans. In particular, older subjects were characterized by impaired CoQ10 status due to their lowered serum CoQ10 concentration and concomitant decrease of CoQ10 redox capacity.

Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms ("CoQ-free") and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES) = 38.0, p = 5.0E(-37)), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p = 5.9E(-31)) and mitochondria function (ES 3.4, p = 1.7E(-5)). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans.

Coenzyme Q(10) is an essential cofactor in the respiratory chain and serves as a potent antioxidant in biological membranes. Recent studies in vitro and in vivo provide evidence that Coenzyme Q(10) is involved in inflammatory processes and lipid metabolism via gene expression. To study these effects at the epigenomic level, C57BL6J mice were supplemented for one week with reduced Coenzyme Q(10) (ubiquinol). Afterwards, gene expression signatures and DNA promoter methylation patterns of selected genes were analysed. Genome-wide transcript profiling in the liver identified 1112 up-regulated and 571 down-regulated transcripts as differentially regulated between ubiquinol-treated and control animals. Text mining and GeneOntology analysis revealed that the "top 20" ubiquinol-regulated genes play a role in lipid metabolism and are functionally connected by the PPARα signalling pathway. With regard to the ubiquinol-induced changes in gene expression of about +3.14-fold (p≤0.05), +2.18-fold (p≤0.01), and -2.13-fold (p≤0.05) for ABCA1, ACYP1, and ACSL1 genes, respectively, hepatic DNA methylation analysis of 282 (sense orientation) and 271 (antisense) CpG units in the respective promoter islands revealed no significant effect of ubiquinol. In conclusion, ubiquinol affects the expression of genes involved in PPARα signalling and lipid metabolism without changing the promoter DNA methylation status in the liver of mice.

Ubiquinol-10 (QH(2)), the reduced form of Coenzyme Q(10) (CoQ(10)) serves as a potent antioxidant of lipid membranes. Because many antioxidants reveal potent anti-inflammatory effects, the influence of QH(2) on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and chemokines were determined in the human monocytic cell line THP-1. Stimulation of cells with LPS resulted in a distinct release of Tumour necrosis factor-alpha (TNF-alpha), Macrophage inflammatory protein-1 alpha (MIP-1alpha), Regulated upon activation, normal T cell expressed and secreted (RANTES) and Monocyte chemotattractant protein-1 (MCP-1). The LPS-induced responses were significantly decreased by pre-incubation of cells with QH(2) to 60.27 +/- 9.3% (p = 0.0009), 48.13 +/- 6.93% (p = 0.0007) and 74.36 +/- 7.25% (p = 0.008) for TNF-alpha, MIP-1alpha and RANTES, respectively. In conclusion, our results indicate anti-inflammatory effects of the reduced form of CoQ(10) on various proinflammatory cytokines and chemokines in vitro.

Coenzyme Q (CoQ) is necessary for mitochondrial energy production and modulates the expression of genes that are important for inflammatory processes, growth and detoxification reactions. A cellular surveillance-activated detoxification and defenses (cSADDs) pathway has been recently identified in C. elegans. The down-regulation of the components of the cSADDs pathway initiates an aversion behavior of the nematode. Here we hypothesized that CoQ regulates genes of the cSADDs pathway. To verify this we generated CoQ-deficient worms ("CoQ-free") and performed whole-genome expression profiling. We found about 30% (120 genes) of the cSADDs pathway genes were differentially regulated under CoQ-deficient condition. Remarkably, 83% of these genes were down-regulated. The majority of the CoQ-sensitive cSADDs pathway genes encode for proteins involved in larval development (enrichment score (ES) = 38.0, p = 5.0E(-37)), aminoacyl-tRNA biosynthesis, proteasome function (ES 8.2, p = 5.9E(-31)) and mitochondria function (ES 3.4, p = 1.7E(-5)). 67% (80 genes) of these genes are categorized as lethal. Thus it is shown for the first time that CoQ regulates a substantial number of essential genes that function in the evolutionary conserved cellular surveillance-activated detoxification and defenses pathway in C. elegans.