Background: Two facts are generally recognized: (1) development of nonalcoholic fatty liver disease (NAFLD) is consistently linked to insulin resistance which has dietary implications and (2) circulating alanine aminotransferase (ALT) levels are reasonable markers predicting NAFLD status. In a recent cross-sectional study employing nondiabetic subjects, ALT values rose steadily within a normal range early in the life cycle but begin decreasing steadily around age 65 years. Objectives: Because of important nutritional implications, the association between ALT levels and aging in a significantly larger population of healthy volunteers was examined for corroborative purposes. A secondary goal was to gain further knowledge concerning mechanisms behind any age-related decline in ALT activity. Methods: Baseline data from over 10,000 physician-approved, nondiabetic subjects (age 21-84 years) of both genders who had volunteered for previous clinical investigations were assessed. Results: In this cross-sectional examination, the line of best fit (weighted) for average yearly circulating ALT levels displayed an upward surge from ages 21 to 64 years with a discernible steady downward decline around 65 years-mimicking earlier results. Examining linear lines of correlation in the younger and older age groups, the following calculations were determined: a significant positive slope for 21 to 64 years, r ¼ 0.42, n ¼ 44, p < 0.005, and a trending negative slope for 65 and beyond, r ¼ À0.43, n ¼ 20, p < 0.057. Using this same datum base, the correlations between age and fasting blood glucose (FBG) mimicked the ALT results by once more showing a similar upward rise in the younger and a steady decline the older group of volunteers. Conclusions: A paradoxical downward age-related (! 65 years) decline of circulating ALT coinciding with a comparable steady decrease in FBG levels was replicated in a larger population of volunteers. The close association of these two chemistries along with other findings suggest that altered glucose-insulin metabolism may participate via "survivor bias" in the ubiquitously found age-related decline of serum ALT-suggesting that nutritional measures could advance optimal health over the life-span.Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; FBG: fasting blood glucose; IR: insulin resistance; MS: metabolic syndrome; NAFLD: nonalcoholic fatty liver disease ARTICLE HISTORY