Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target

被引：239

作者：

Sorgdrager, Freek J. H. ^{[1
,2
,3
,4
,5
]}

Naude, Petrus J. W. ^{[3
,4
,6
]}

Kema, Ido P. ^{[5
]}

Nollen, Ellen A. ^{[1
]}

De Deyn, Peter P. ^{[2
,3
,4
,7
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, European Res Inst Biol Ageing, Groningen, Netherlands

[2] Univ Antwerp, Inst Born Bunge, Dept Biomed Sci, Lab Neurochem & Behav, Antwerp, Belgium

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Neurol, Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Alzheimer Ctr, Groningen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands

[6] Univ Groningen, Groningen Inst Evolutionary Life Sci GELIFES, Dept Mol Neurobiol, Groningen, Netherlands

[7] Hosp Network Antwerp ZNA Middelheim & Hoge Beuk, Memory Clin, Dept Neurol, Antwerp, Belgium

来源：

FRONTIERS IN IMMUNOLOGY | 2019年 / 10卷

关键词：

tryptophan; aging; inflammation; kynurenine; inflammaging; 2; 3-dioxygenase (TDO); indoleamine; 3 dioxygenases (IDO); ARYL-HYDROCARBON RECEPTOR; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; KYNURENINE PATHWAY; CARDIOVASCULAR RISK; APOPTOTIC CELLS; OLDER-ADULTS; T-CELLS; ACID; TOLERANCE; INHIBITION;

D O I：

10.3389/fimmu.2019.02565

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：8

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