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Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster

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Abstract

Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals. In this study, we aimed to understand the effect of rutin on extending longevity in Drosophila melanogaster. Male and female flies were administered with a range of rutin doses (100–800 µM) to analyse whether rutin mediated lifespan-extension by hormesis. Effect of rutin on physiological parameters like food intake, fecundity, climbing activity, development and resistance to various stresses was also studied. Lifespan assays showed that rutin at 200 and 400 µM significantly extended median lifespan in both male and female flies beyond which flies exhibited drastically reduced longevity. Increase in survival at 400 µM was associated with reduced food intake and fecundity. Flies exhibited improved climbing capability with both 200 and 400 µM rutin. Flies fed with 100 and 200 µM rutin exhibited enhanced survival upon exposure to oxidative stress with 400 µM rutin exhibiting no improvement in median lifespan following oxidative stress. Analysis of endogenous peroxide upon treatment with rutin (100–400 µM) with or without 5% H2O2 showed elevated levels of endogenous peroxide with 400 µM rutin whereas no increase in hydrogen peroxide level was observed with rutin at 100 and 200 µM. Finally, gene expression studies in male flies revealed that rutin treatment at 200 and/or 400 µM elevated transcript levels of dFoxO, MnSod, Cat, dTsc1, dTsc2, Thor, dAtg1, dAtg5 and dAtg7 and reduced transcript levels of dTor. Collectively, rutin at 200 and 400 µM improved longevity in flies; 200 µM rutin acted as a mild stressor to prolong lifespan in flies by mediating hormesis whereas 400 µM, being a high dose for best positive effects.

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Acknowledgements

We thank Dr. N.B. Ramachandra at Mysore University, National Drosophila Stock Centre, India, for providing the wild-type Canton-S fly strain.

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  1. 206, Structural Biology Lab, Centre for Biomedical Research, School of Bio Sciences & Technology, VIT University, Vellore, Tamil Nadu, India

    Debarati Chattopadhyay, Atith Chitnis, Aishwarya Talekar, Prajakta Mulay, Manyata Makkar, Joel James & Kavitha Thirumurugan

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  1. Debarati Chattopadhyay
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  2. Atith Chitnis
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Supplementary material 1 (DOCX 12 kb)

Fig. S1

Effect of rutin on longevity in male and female flies. (A) Survival curve of adult male flies. (B) Survival curve of adult female flies. Data represented as percentage survival of flies as function of time in days with error bars denoting 95% CI. Survival curves plotted using Kaplan–Meier survival analysis. For each sex and treatment, replicates = 10, n = 30 flies in each replicate, total flies = 3600. Supplementary material 2 (BMP 493 kb)

Fig. S2

Effect of rutin on day-wise reproductive output in females. Data represented as mean number of eggs laid by a female per day for 15 days with error bars denoting SEM. Table S1 includes day-wise significance analysis between control and rutin treated groups. 10 replicate vials were set up for each diet, with two males and two females in each replicate. Supplementary material 3 (BMP 184 kb)

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Chattopadhyay, D., Chitnis, A., Talekar, A. et al. Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster . Biogerontology 18, 397–411 (2017). https://doi.org/10.1007/s10522-017-9700-1

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