Chronobiotics Kl001 And Ks15 Extend Lifespan And Modify Circadian Rhythms Of Drosophila Melanogaster

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 mu M solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 mu M 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 mu M 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 mu M solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 mu M 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.