Abstract

Aging is the major risk factor for many human diseases and degeneration. Thus, clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted. In traditional Chinese medicine (TCM), some were claimed to slow down aging. Qingyangshen (Cynanchum otophyllum schneid) is such a TCM. Here, we assayed the longevity effect of compound Otophylloside B (Ot B), a C-21 steroidal glycoside isolated from Qingyangshen, in Caenorhabditis elegans, which is a popular model for aging research. Our results showed that Ot B could modestly extend the lifespan of C. elegans, delay the age-related decline of body movement and improve the stress resistance. Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16. Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor (daf-2). In addition, Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis, for lifespan extension.Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-015-0064-4) contains supplementary material, which is available to authorized users.

Highlights

  • The identification of chemical interventions that can ameliorate age-related illness and degeneration has been an important aspect of current aging research

  • We found that Otophylloside B (Ot B) could lengthen the lifespan of C. elegans, delay the age-related decline of body movement and improve heat resistance

  • To identify compounds that might slow aging and extend lifespan in C. elegans, we assayed a panel of compounds with pharmacological effects or bioactivity related to improving health condition or reducing the age-related diseases, such as qingyangshengenin, otophylloside A, otophylloside B and b-sitosterol, which were isolated from C. otophyllum

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Summary

Introduction

The identification of chemical interventions that can ameliorate age-related illness and degeneration has been an important aspect of current aging research. A number of compounds have been reported to extend C. elegans lifespan, such as a variety of antioxidant compounds [5, 6], complex mixtures derived from plants [7, 8], a sirtuin activator resveratrol [9, 10], an antihyperglycemic drug metformin [11, 12], TOR inhibition rapamycin [13], nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. aspirin), as well as anticonvulsant medicines (e.g. ethosuximide) [14, 15]. The effect of Ot B on lifespan could share similar phenotypic features as IIS signaling pathway because it failed to further extend the lifespan of long-live insulin-like receptor mutant daf-2 [17]. Ot B extending the lifespan requires SIR-2.1 and CLK-1

Results and Discussion
Ot B Might Extend Lifespan by Mediating to Reduce Mitochondrial Respiration
Conclusion
General Experimental Procedures
Lifespan Assay
Thermo-Tolerance and Body Movement Analysis
DAF-16:: GFP Localization Assay
RNA Interference Experiments
Quantitative RT-PCR Assay
Full Text
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