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Chrysophanol delays aging via insulin/IGF-1 signaling pathway

Hongjiao Zhang1, Jun Xiong2, Qingyao Wang2

  • 1Institute 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.

Free Radical Biology & Medicine
|March 14, 2025
PubMed

Insights

Chrysophanol (Chr) extends lifespan and healthspan in worms and mice by activating the insulin signaling pathway. This natural compound also reduces aging markers, showing promise for treating age-related diseases.

Area of Science:

  • Gerontology and molecular biology
  • Pharmacology and natural products

Background:

  • Aging is a major risk factor for numerous diseases, including cancer and neurodegeneration.
  • Targeting conserved aging pathways offers a strategy for lifespan extension and age-related disease mitigation.
  • Chrysophanol (Chr), a natural anthraquinone, has known anti-cancer and anti-inflammatory effects, but its anti-aging role is unexplored.

Purpose of the Study:

  • To investigate the effect of Chrysophanol (Chr) on aging and lifespan in model organisms.
  • To elucidate the molecular mechanisms underlying Chr's potential anti-aging properties.
  • To evaluate Chr as a therapeutic candidate for age-related conditions.

Main Methods:

  • Lifespan and healthspan assays were performed in Caenorhabditis elegans.
  • Longevity studies were conducted in natural aging, doxorubicin-induced aging, and transgenic mice models.
  • The involvement of the insulin/IGF-1 signaling pathway was investigated.
  • Senescence-associated secretory phenotypes (SASPs) and antioxidant gene expression were analyzed.

Main Results:

  • Chr significantly extended lifespan and healthspan in C. elegans by activating the DAF-2/DAF-16 insulin signaling pathway.
  • Chr promoted longevity across different aging mouse models, mediated by the conserved Insulin/IGF-1 signaling pathway.
  • Chr treatment modulated SASPs and upregulated antioxidant gene expression, delaying aging phenotypes.

Conclusions:

  • Chrysophanol (Chr) demonstrates potent anti-aging effects conserved from invertebrates to mammals.
  • The compound acts via the evolutionarily conserved Insulin/IGF-1 signaling pathway.
  • Chr is a promising natural product for developing interventions against aging and associated diseases.
Keywords:
AgingChrysophanolInsulin/IGF-1 signaling pathwayLifespan

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