Kynurenine pathway and human systems.

Abstract

The essential amino acid L-tryptophan (Trp) appears to play an important role in aging by acting as a general regulator of protein homeostasis. The major route of Trp degradation, the kynurenine pathway (KP), produces a range of biologically active metabolites that can impact or be impacted by a variety of body systems, including the endocrine, haemopoietic, immune, intermediary metabolism and neuronal systems, with the end product of the KP, NAD+, being essential for vital cellular processes. An account of the pathway, its regulation and functions is presented in relation to body systems with a summary of previous studies of the impact of aging on the pathway enzymes and metabolites. A low-grade inflammatory environment characterized by elevation of cytokines and other immune modulators and consequent disturbances in KP activity develops with aging. The multifactorial nature of the aging process necessitates assessment of factors determining the progression of this mild dysfunction to age-related diseases and developing strategies aimed at arresting and reversing this progression.