Increasing production of homocysteine and neopterin and degradation of tryptophan with older age.
OBJECTIVE
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, B6, and/or B12.


METHODS
Serum concentrations of neopterin, homocysteine, tryptophan and kynurenine, and of vitamins folate and B12 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 B12 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.
Institute of Medical Chemistry and Biochemistry, Leopold-Franzens University, Innsbruck, Austria.
Barbara
B
Frick
Katharina
K
Schroecksnadel
Gabriele
G
Neurauter
Friedrich
F
Leblhuber
Dietmar
D
Fuchs
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D049308:Dioxygenases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006710:Homocysteine / Q000096:biosynthesis*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000096:biosynthesis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism*; D014805:Vitamin B 12 / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D006710:Homocysteine; D007737:Kynurenine; D019798:Neopterin; D007371:Interferon-gamma; D014364:Tryptophan; D005492:Folic Acid; D049308:Dioxygenases; D014805:Vitamin B 12