Clinical insights into the kynurenine pathway in age-related diseases

Accumulating evidence from diverse experiments, including heterochronic parabiosis-the surgical joining of two animals of different ages-has highlighted the importance of systemic factors in the progressive functional decline of various organs and tissues during aging. The major metabolic pathway of tryptophan, an essential amino acid in humans, is the kynurenine pathway (KP) in which indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the conversion of tryptophan into kynurenine. Importantly, circulating kynurenine produced by this enzymatic breakdown, as a primary driver of the aging process, has been linked to higher mortality in humans. This review discusses the potential roles of tryptophan derivatives as biomarkers for the risk of frailty in the elderly, based on human observational studies as well as the KP as a therapeutic target for age-related diseases.