Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target.

Freek J H Sorgdrager, Petrus J W Naudé, Ido P Kema, Ellen A Nollen, Peter P De Deyn

Journal: Frontiers in immunology 2020;10():2565

PMID: 31736978

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Plain Language Summary

Inflammation is a normal physiological process activated by the immune system in response to injury or infection. As we age, the immune system changes and the balance between pro- and anti-inflammatory agents can shift. This causes a chronic inflammatory state referred to as inflammaging. The rate of inflammaging is strongly associated with age-related disability, disease and mortality. The way in which the essential amino acid tryptophan (Trp) is broken down affects inflammation. If it is converted to kynurenine (Kyn) and its metabolites, inflammation is modulated. Studies have shown that the Kyn/Trp ratio, measured in blood, is strongly associated with ageing in humans. It could therefore be a useful marker to predict the onset of age-related diseases. This review discusses the metabolism of Trp and the links to inflammation. The authors hypothesize how intervening in these pathways could impact health- and lifespan. Future studies are needed to confirm the value of Trp metabolism as a biomarker for (un)healthy ageing and as drug target for inflammaging-related disease.

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.

Address: European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Laboratory of Neurochemistry and Behavior, Department of Biomedical Sciences, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.; Department of Neurology and Alzheimer Center, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.; Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen, Netherlands.; Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.

DOI: 10.3389/fimmu.2019.02565

Patient Centred Factor

Mediators: Inflammation/tryptophan

Clinical Imbalances

Neurological Immune and inflammation

Nutrition Evidence Keywords

Immune system

Bioactive Substances

Tryptophan Kynurenine

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/olderadulthealth.html

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-IDO1-3

MeSH Terms: Aging, Animals, Biomarkers, Chronic Disease, Disease Susceptibility, Humans, Immunomodulation, Inflammation, Molecular Targeted Therapy, Tryptophan