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Significant decrease in the level of lipid antioxidants (measured from the kinetics of the induced chemiluminescence in brain homogenate) and of the hydrophilic antioxidant carnosine as well was observed in the brain of 14-16-month-old mice of SAMP1 line, which is characterized by accelerated accumulation of senile features, in comparison with the control line SAMR1. In the brain of SAMP1 animals the activity of cytosolic Cu/Zn-containing superoxide dismutase (SOD) was reduced, while the activity of membrane-bound Mn-SOD was at an extremely low level. The activity of glutathione-dependent enzymes (glutathione peroxidase, glutathione reductase, and glutathione transferase) did not differ in the brain of SAMP1 and SAMR1 animals, and catalase activity was similarly low in both cases. At the same time, excess concentration of excitotoxic compounds, significantly exceeding that for the control line, was determined in the brain and blood of SAMP1 animals. The activity of glutathione enzymes in liver and heart as well as the activity of cytosolic Cu/Zn-SOD in liver did not differ in the two studied lines, while the activity of erythrocyte glutathione peroxidase was slightly increased, and the activity of liver catalase and erythrocyte Cu/Zn-SOD was significantly decreased for SAMP1 compared with SAMR1. The results demonstrate that the accelerated ageing of SAMP1 animals is connected to a significant extent with the decreased efficiency of the systems utilizing reactive oxygen species (ROS) in tissues.

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This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a “regulating valve” that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity.

Background: The human organism is a complex superorganism including numerous eukaryotic, eubacterial, and archaean cells. The qualitative and quantitative assessment of the microbiota toxicity of chemical agents, i.e., their inhibitory effects on the microbial inhabitants of the human organism in health and disease, seems to hold much value in this context. In this work, a bacterial luminescence-based express test system for microbiota toxicity is applied to neurotransmitters such as serotonin, dopamine, norepinephrine, and histamine. Methods:The biosensor was based on a GM Escherichia coli K12 strain (TGI) that contained the lux operon of the luminescent soil bacterium Photorhabdus luminescencens ZMI. The biosensor was exposed to the action of the tested neurotransmitters for 5 to 60 minutes The intensity of bacterial luminescence (counts . sec -1 ) was monitored in the control and the experimental samples with a Biotoks 6 ms luminometer (Russia); the toxicity index (T) of the neurotransmitters was determined.Results: A marked toxic effect on bioluminescence was produced by serotonin, histamine, and dopamine at concentrations exceeding 80 µg/ml, 100 µg/ml, and 1 mg/ml, respectively. At lower concentration, these neurotransmitters were "negatively toxic", i.e. stimulatory in terms of the effect on bacterial luminescence. In contrast, norepinephrine inhibited luminescence at all concentrations tested. Conclusions:The bacterial luminescence-based testing method is applicable to the assessment of the destructive and stimulatory effects of neurotransmitters; the data obtained are of microbiological and clinical relevance.