Tetrahydroxystilbene glucoside extends mouse life span via upregulating neural klotho and downregulating neural insulin or insulin-like growth factor 1

Neurobiol Aging. 2015 Mar;36(3):1462-70. doi: 10.1016/j.neurobiolaging.2014.11.002. Epub 2014 Dec 18.


A Chinese herb, Polygonatum multiflorum, has been reported to prolong animal life span, but the relevant molecular mechanism remains unclear. Tetrahydroxystilbene glucoside (TSG) is one main component of P. multiflorum and may contribute to extending life span of mammals. On the other hand, neuronal insulin signaling mediates the life span of mammals. Therefore, we investigated the effects of TSG on memory ability, life span, and the neural insulin signaling in the senescence-accelerated prone mouse (SAMP8). TSG improved the memory ability significantly (p < 0.01, compared with a control group). TSG prolonged the life span of SAMP8 by 17% at the most (p < 0.01, compared with a control group). TSG increased the protein level of neural klotho and reduced the levels of neural insulin, insulin-receptor, insulin-like growth factor-1, and insulin-like growth factor-1 receptor in the brain of SAMP8 (p < 0.01, compared with a control group). All these proteins are key factors of the pathways related to neural insulin/IGF-1 signaling. These findings suggest that TSG has anti-aging effects on mammals. From these results, TSG from P. multiflorum should be developed as a potential anti-age drug.

Keywords: Aging; Insulin; Insulin-like growth factor 1; Klotho; Senescence-accelerated prone mouse; Tetrahydroxystilbene glucoside.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects*
  • Aging / genetics*
  • Animals
  • Cells, Cultured
  • Down-Regulation / drug effects*
  • Gene Expression Regulation, Developmental / drug effects*
  • Glucosides / pharmacology*
  • Glucuronidase / genetics*
  • Glucuronidase / metabolism*
  • Insulin / genetics*
  • Insulin / metabolism*
  • Insulin / physiology
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / physiology
  • Klotho Proteins
  • Longevity / drug effects*
  • Longevity / genetics*
  • Memory / drug effects
  • Mice, Inbred Strains
  • Models, Animal
  • Polygonatum / chemistry*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stilbenes / pharmacology*
  • Up-Regulation / drug effects*


  • Glucosides
  • Insulin
  • Stilbenes
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • Insulin-Like Growth Factor I
  • Glucuronidase
  • Klotho Proteins