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Updated: Oct 22, 2025
Circadian Entrainment of Drosophila Melanogaster
Published on: June 3, 2020
Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster
Ilya A Solovev1,2, Mikhail V Shaposhnikov1, Alexey A Moskalev1
1Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Centre, Ural Branch, Russian Academy of Sciences, Kommunisticheskaya Str. 28, 167982 Syktyvkar, Russia.
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.
Insights
Chronobiotics KL001 and KS15 targeting CRY extended lifespan and improved healthspan in male fruit flies. These compounds show potential for geroprotective effects by modulating circadian rhythms and metabolic processes.
Area of Science:
- Gerontology
- Chronobiology
- Molecular Biology
Background:
- Circadian rhythms, regulated by the biological clock, influence aging processes.
- Chronobiotics are compounds that modify circadian rhythms by targeting clock-associated molecular mechanisms.
Purpose of the Study:
- To investigate the effects of KL001 and KS15, which target CRY (cryptochrome), on lifespan, locomotor activity, and circadian rhythms in Drosophila melanogaster.
Main Methods:
- Administration of KL001 and KS15 at specific concentrations to male and female fruit flies.
- Assessment of median and maximum lifespan, locomotor activity under different light conditions, and circadian rhythm parameters.
- Measurement of starvation resistance to evaluate metabolic health.
Main Results:
- KL001 (5 µM) showed a slight increase in median lifespan (2%) and a 14% increase in maximum lifespan in male flies.
- KS15 (10 µM) extended median lifespan by 8% in male flies; no significant effects were observed in females.
- KL001 improved locomotor activity and circadian rhythm robustness in male flies, and enhanced starvation resistance by up to 50%.
Conclusions:
- KL001 and KS15 demonstrate geroprotective effects in male Drosophila, potentially through mechanisms involving CRY modulation and improved metabolic utilization of glucose during starvation.
- The compounds' effects on lifespan and activity highlight the role of circadian clock regulators in aging.
- Further research is warranted to explore the precise molecular pathways and potential therapeutic applications in aging.
