Chrysophanol delays aging via insulin/IGF-1 signaling pathway.

Hongjiao Zhang, Jun Xiong, Qingyao Wang, Qiuyu Song, Lingjie Meng, Han Zhang, Yuxin Bao, Fang Liu, Yi Xiao

Institute of Life Sciences, Zunyi Medical University, Zunyi Guizhou, 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi Guizhou, 563000, China; Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.Institute of Life Sciences, Zunyi Medical University, Zunyi Guizhou, 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi Guizhou, 563000, China; Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China. · pubmed

Paper

Abstract

Aging is inevitable processes which play a significant role in the development of various diseases, including cardiovascular diseases, neurodegenerative disorders, and cancers. The extension of lifespan and the improvement of age-related diseases can potentially be achieved by targeting evolutionarily conserved pathways and mechanisms through pharmacological interventions. Chrysophanol (Chr), a naturally occurring anthraquinone compound primarily derived from rhubarb of the Polygonaceae family, exhibits a wide range of pharmacological activities, including anti-cancer, anti-inflammatory, and anti-bacterial effects. However, its role in regulating aging remains unclear. In this study, we discovered that Chr extends both lifespan and healthspan in Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin signaling pathway. Furthermore, we observed that Chr promoted longevity in natural aging mice, doxorubicin-induced aging mice, and transgenic mice through the conserved Insulin/IGF-1 signaling pathway. Additionally, Chr also influenced senescence-associated secretory phenotypes (SASPs) and enhanced the expression of antioxidant genes, contributing to delayed aging. These findings highlight that Chr exerts anti-aging effects from C. elegans to mammals via the evolutionarily conserved Insulin/IGF-1 signaling pathway, positioning Chr as a promising candidate for the prevention and treatment of aging and age-related diseases.

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Research summary

Chrysophanol extends lifespan and healthspan in C. elegans and mammals by activating the insulin/IGF-1 signaling pathway. The study addresses the root causes of aging by exploring a compound that influences conserved signaling pathways associated with longevity and age-related diseases.

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