Journal
CLOCKS & SLEEP
Volume 3, Issue 3, Pages 429-441Publisher
MDPI
DOI: 10.3390/clockssleep3030030
Keywords
chronobiotics; geroprotectors; cryptochrome; KL001; KS15; Drosophila melanogaster
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Funding
- Russian Foundation for Basic Research [19-34-90058]
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The study showed that drugs targeting CRY, such as KL001 and KS15, have effects on lifespan, locomotor activity, and circadian rhythms in Drosophila melanogaster. KL001 had a protective effect on lifespan and improved locomotor activity in male flies, while KS15 extended the median lifespan of male flies.
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.
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