Isotschimgine promotes lifespan, healthspan and neuroprotection of Caenorhabditis elegans via the activation of nuclear hormone receptors.

Hang Shi, Xiaoyan Gao, Jing Yu, Lijun Zhang, Bingbing Fan, Ying Liu, Xinyi Wang, Shengjie Fan, Cheng Huang

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. · pubmed

Paper

Abstract

Isotschimgine (ITG) is a bornane-type monoterpenoid derivative naturally occurring in genus Ferula plants and propolis. Its effects on aging and the underlying mechanisms are not yet well understood. This study employed Caenorhabditis elegans (C. elegans) as a model organism to evaluate the potential of ITG in extending lifespan, enhancing healthspan, and promoting neuroprotection, while exploring the underlying mechanisms involved. The results showed that ITG extended the lifespan and healthspan of C. elegans, significantly enhanced stress resistance and detoxification functions. Studies on mutants and qPCR data indicated that ITG-mediated lifespan extension was modulated by the insulin/IGF-1 signaling pathway and nuclear hormone receptors. Furthermore, ITG markedly increased stress-responsive genes, including daf-16 and its downstream genes sod-3 and hsp-16.2, as well as NHR downstream detoxification-related genes cyp35a1, cyp35b3, cyp35c1, gst-4, pgp-3 and pgp-13. Additionally, ITG alleviated β-amyloid-induced paralysis and behavioral dysfunction in transgenic C. elegans strains. The neuroprotective efficacy of ITG was weakened by RNAi knockdown of nuclear hormone receptors daf-12 and nhr-8. Overall, our study identifies ITG as a potential compound for promoting longevity and neuroprotection, mediated through nuclear hormone receptors.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the effects of Isotschimgine on lifespan and healthspan in C. elegans, focusing on mechanisms related to aging and neuroprotection. While it contributes to the understanding of potential compounds that may influence longevity, the findings appear to be incremental rather than groundbreaking. The study provides solid evidence for the role of nuclear hormone receptors in lifespan extension but lacks broader implications that would significantly advance the field of longevity research.

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