The age-related increase in N-methyl-2-pyridone-5-carboxamide (NAD catabolite) in human plasma

Abstract

N-Methyl-2-pyridone-5-carboxamide (2PY) is a major catabolite of NAD, which is excreted in the urine. Assay of plasma concentration and urine exrection of 2PY is of interest for monitoring niacin nutritional state and NAD catabolism. Aging has major impact on number of metabolic processes, but its effect on plasma and tissue 2PY concentration has not been studied so far. The present study was undertaken to investigate the effect of aging on human plasma 2PY concentration. Blood samples were collected from 78 (56 females and 22 males) healthy subjects at different age ranging from 5 to 90 years. Plasma ultrafiltrates were analyzed with liquid chromatography/mass spectrometry (LC/MS) for 2PY concentration. 2PY concentration was also evaluated in plasma and liver of young (2 month) and old (24 month) rats. The mean plasma 2PY concentration in young (5-16 years old) healthy subjects was 0.39 +/- 0.22 micromol/l while in old healthy subjects (50-90 years old) it was approximately 2.6-fold higher. No gender differences was found in plasma 2PY concentration. Univariate regression analysis displayed positive correlation between age and human plasma 2PY concentration (r = 0.57, p < 0.01) and between age and 2PY/creatinine ratio (r = 0.4, p < 0.01). Multivariate regression analysis indicates that both age and plasma creatinine concentrations were independently correlated with the increase in plasma 2PY concentration. Daily 2PY excretion with urine corrected for weight was approximately 30% lower in old subjects than in young humans. 2PY concentrations in liver and plasma of 2-month-old rats were lower than in 24-month-old rats. In conclusion, our results demonstrated that human plasma 2PY concentration increases with age. This could be a consequence of both decreased renal excretion and increased production in the the liver or other organs. Our results indicate that age should be taken into consideration in the interpretation of plasma 2PY concentration.