Taurine represses age-associated gut hyperplasia in Drosophila via counteracting endoplasmic reticulum stress

Aging Cell. 2021 Mar;20(3):e13319. doi: 10.1111/acel.13319. Epub 2021 Feb 9.

Abstract

As they age, adult stem cells become more prone to functional decline, which is responsible for aging-associated tissue degeneration and diseases. One goal of aging research is to identify drugs that can repair age-associated tissue degeneration. Multiple organ development-related signaling pathways have recently been demonstrated to have functions in tissue homeostasis and aging process. Therefore, in this study, we tested several chemicals that are essential for organ development to assess their ability to delay intestinal stem cell (ISC) aging and promote gut function in adult Drosophila. We found that taurine, a free amino acid that supports neurological development and tissue metabolism in humans, represses ISC hyperproliferation and restrains the intestinal functional decline seen in aged animals. We found that taurine represses age-associated ISC hyperproliferation through a mechanism that eliminated endoplasmic reticulum (ER) stress by upregulation of the target genes of unfolded protein response in the ER (UPRER ) and inhibiting the c-Jun N-terminal kinase (JNK) signaling. Our findings show that taurine plays a critical role in delaying the aging process in stem cells and suggest that it may be used as a natural compound for the treatment of age-associated, or damage-induced intestinal dysfunction in humans.

Keywords: ER stress; JNK signaling; aging; gut; intestinal stem cell; taurine; unfolded protein response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Animals
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Endoplasmic Reticulum Stress* / drug effects
  • Endoplasmic Reticulum Stress* / genetics
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / pathology*
  • Gene Expression Regulation / drug effects
  • Hyperplasia
  • Intestines / pathology
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Phenotype
  • Stem Cells / drug effects
  • Stem Cells / pathology
  • Taurine / administration & dosage
  • Taurine / pharmacology*
  • Unfolded Protein Response / drug effects
  • Unfolded Protein Response / genetics

Substances

  • Taurine
  • JNK Mitogen-Activated Protein Kinases