Ameliorative Effect of Dietary Tryptophan on Neurodegeneration and Inflammation in d-Galactose-Induced Aging Mice with the Potential Mechanism Relying on AMPK/SIRT1/PGC-1α Pathway and Gut Microbiota

J Agric Food Chem. 2021 Apr 28;69(16):4732-4744. doi: 10.1021/acs.jafc.1c00706. Epub 2021 Apr 19.

Abstract

Dietary tryptophan affects intestinal homeostasis and neurogenesis, whereas the underlying mechanism and the reciprocal interaction between tryptophan and gut microbiota in aging are unclear. This investigation was performed to determine the effect and mechanism of tryptophan on intestinal- and neuro- health in aging. In present study, the 0.4% tryptophan diet significantly ameliorated the oxidative stress and inflammation in the aging mice, potentially through the regulation of 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and nuclear factor κB (NF-κB) pathways. The 0.4% tryptophan diet increased the levels of indoles in colon contents, which indicated the potential contribution of tryptophan metabolites. Microbiome analysis revealed that the 0.4% tryptophan diet raised the relative abundance of Akkermansia in aging. The ameliorated effect of 0.4% tryptophan on neurodegeneration and neuroinflammation was summarized to potentially rely on the brain-derived neurotrophic factor- (BDNF) and NF-κB-related pathways. These findings provide the research evidence for the beneficial effect of tryptophan on aging.

Keywords: AMPK; aging; gut microbiota; neurodegeneration; tryptophan.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • Aging
  • Animals
  • Diet*
  • Galactose
  • Gastrointestinal Microbiome*
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Mice
  • Neurodegenerative Diseases / drug therapy*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sirtuin 1 / genetics
  • Tryptophan / administration & dosage*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Tryptophan
  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Galactose