Increasing production of homocysteine and neopterin and degradation of tryptophan with older age

Objectives: Aging is associated with an increased frequency of abnormal immune system function, which may cause infections, autoimmune diseases, and cardiovascular or neurodegenerative disorders. Th1-type cytokine interferon-gamma (IFN-gamma) induces neopterin production as well as tryptophan degradation via indoleamine (2,3)-dioxygenase (IDO), and quantification of these biochemical alterations allows one to monitor immune system activation. Homocysteine is known to be elevated in the elderly, which is possibly due to an insufficient availability of folate, B-6, and/or B-12. Design and Methods: Serum concentrations of neopterin, homocysteine, tryptophan and kynurenine, and of vitamins folate and B-12 were measured in 43 healthy individuals (21 females, 22 males) aged 34-93 years. The ratio of the concentration of the product of IDO, kynurenine, versus the substrate tryptophan (kyn/trp) was calculated to estimate IDO activity. Results: Comparing three age groups of similar size (34-60, 61-71, and 72-93 years), neopterin and homocysteine concentrations as well as the kyn/trp ratio were found to increase with older age (all P < 0.01). Folate concentrations were lower in the middle-aged group as compared with the other two subgroups of individuals. Vitamin B-12 concentrations did not differ between groups. Positive correlations were found between kyn/trp and neopterin and homocysteine concentrations (all P < 0.01). Conclusions: Increasing neopterin concentrations and kyn/trp with older age are in line with the view that aging in healthy people is associated with immune activation especially of the T-cell/macrophage system. (C) 2004 The Canadian Society of Clinical Chemists. All rights reserved.