Abstract
Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.
Highlights
Natural selection determined the formation of diverse molecular systems responsible for reception and transduction of light signals as time in the biosphere as well as in society has the central role
Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms
KL001 5 μM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001)
Summary
Natural selection determined the formation of diverse molecular systems responsible for reception and transduction of light signals as time in the biosphere as well as in society has the central role. The molecular timer is called the circadian (circa—near, dian—day) clock or molecular oscillator [1]. The clock is characterized by the robustness of generated rhythms [2]. The periodicity found in behavioural and biochemical patterns and in gene expression profiles is synchronized with the rhythms of Earth’s rotation by zeitgebers [3]. Zeitgeber is a dominating stimulus which resets the clock. There are different zeitgebers like light, temperature, food intake, physical activity and numerous endogenous metabolites (Heyde, I.; Oster, 2021) [4]. We sought to describe the oscillator of Drosophila melanogaster which is the model used in our study
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