CALORIC RESTRICTION DECREASES AGE-DEPENDENT ACCUMULATION OF THE GLYCOXIDATION PRODUCTS, N-EPSILON-(CARBOXYMETHYL)LYSINE AND PENTOSIDINE, IN RAT SKIN COLLAGEN

Nonenzymatic glycation of body proteins and subsequent advanced glycation reactions have been implicated in the aging process, while caloric restriction (CR) in rodents results in an increase in both mean and maximum life span. We have evaluated the effect of chronic (25 months) CR on glycation of blood proteins and accumulation of advanced glycation and oxidation (glycoxidation) products, N-epsilon-(carboxymethl)lysine (CML), and pentosidine, in skin collagen. Brown-Norway rats, fed ad libitum (AL)from birth, were divided into two equal groups at 4 months of age and placed on AL or CR diets (CR = 60% of AL diet). Cohorts of animals were sacrificed at 7, 13, and 25 months after the initiation of CR. At necropsy glycated hemoglobin was measured by affinity HPLC and glycated plasma protein by the fructosamine assay; extracts of skin collagen were analyzed by gas chromatography-mass spectrometry for CML and by reversed-phase HPLC for pentosidine. Glycation of hemoglobin, plasma proteins, and skin collagen was decreased significantly (18-33%) by CR. Concentrations of CML and pentosidine increased significantly with age in skirt collagen in both AL and CR animals; however, CR significantly reduced levels of CML (25%), pentosidine (50%), and fluorescence (15%) in collagen in the oldest rats. We conclude that CR reduces the extent of glycation of blood and tissue proteins and the age-related accumulation of glycoxidation products in skin collagen.