Abstract
Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of handelin.
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Acknowledgements
This work was supported by the National Key R&D Program, Ministry of Science and Technology of China (2020YFC2002900), the National Natural Science Foundation of China (No. 81873814, No. 91649120, No. 81560697), Jiangxi Province (20192BCB23004, 2018ACB21036, 20181BCD40001) and Yunnan Province (D-2017009), Chinese Academy of Science (GREKF18-10) and Postgraduate Innovation Special Fund Project of Nanchang University (YC2019-B027).
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Supplementary file1 (PDF 270 kb)—Figure S1 Chromatograms of handelin content in CLE obtained by different extraction methods were detected. a Standard, b Water extraction, c Ethanol extraction.
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Supplementary file2 (PDF 347 kb)—Figure S2 Lifespans of wildtype N2 worms treated with different concentration of handelin from L4 stage were assessed (n = 126 for vehicle group, n = 126 for 12.5 μM group, n = 136 for 25 μM group and n = 131 for 50 μM group). The datas are representative of at least three independent experiments. The survival curves were plotted using Kaplan–Meier survival analysis and significance levels were estimated by long-rank test.
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Supplementary file3 (PDF 34258 kb)—Figure S3 SJ4103 strain worms expressing GFP in body wall muscle cell mitochondria were treated with 50 μM handelin or with vehicle from L4 stage for indicated days from hatching and visualized under confocal microscopy as described in Methods. Merge diagram of fluorescence and visible light. Scale bar, 100 μm.
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Supplementary file4 (PDF 338 kb)—Figure S4 Gene expression of skn-1, gst-4, gst-5 and gst-33 in natural aging and handelin treatment.
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Zhang, H., Qin, J., Lan, X. et al. Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function. Biogerontology 23, 115–128 (2022). https://doi.org/10.1007/s10522-022-09950-5
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DOI: https://doi.org/10.1007/s10522-022-09950-5