Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target

Front Immunol. 2019 Oct 30:10:2565. doi: 10.3389/fimmu.2019.02565. eCollection 2019.

Abstract

Inflammation aims to restore tissue homeostasis after injury or infection. Age-related decline of tissue homeostasis causes a physiological low-grade chronic inflammatory phenotype known as inflammaging that is involved in many age-related diseases. Activation of tryptophan (Trp) metabolism along the kynurenine (Kyn) pathway prevents hyperinflammation and induces long-term immune tolerance. Systemic Trp and Kyn levels change upon aging and in age-related diseases. Moreover, modulation of Trp metabolism can either aggravate or prevent inflammaging-related diseases. In this review, we discuss how age-related Kyn/Trp activation is necessary to control inflammaging and alters the functioning of other metabolic faiths of Trp including Kyn metabolites, microbiota-derived indoles and nicotinamide adenine dinucleotide (NAD+). We explore the potential of the Kyn/Trp ratio as a biomarker of inflammaging and discuss how intervening in Trp metabolism might extend health- and lifespan.

Keywords: aging; indoleamine 2,3 dioxygenases (IDO); inflammaging; inflammation; kynurenine; tryptophan; tryptophan 2,3-dioxygenase (TDO).

Publication types

  • Review

MeSH terms

  • Aging / metabolism*
  • Animals
  • Biomarkers
  • Chronic Disease
  • Disease Susceptibility*
  • Humans
  • Immunomodulation
  • Inflammation / drug therapy
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Molecular Targeted Therapy
  • Tryptophan / metabolism*

Substances

  • Biomarkers
  • Tryptophan