Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

Version 1 : Received: 21 July 2021 / Approved: 22 July 2021 / Online: 22 July 2021 (13:39:54 CEST)

A peer-reviewed article of this Preprint also exists.

Solovev, I.A.; Shaposhnikov, M.V.; Moskalev, A.A. Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster. Clocks & Sleep 2021, 3, 429-441. Solovev, I.A.; Shaposhnikov, M.V.; Moskalev, A.A. Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster. Clocks & Sleep 2021, 3, 429-441.

Journal reference: Clocks & Sleep 2021, 3, 30
DOI: 10.3390/clockssleep3030030

Abstract

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind 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 imagos (p<0.05) and elevated morning activity peak in aged imagos and modified robustness of 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.

Keywords

Chronobiotics; geroprotectors; cryptochrome; KL001; KS15; Drosophila melanogaster

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