(03-11-09) Protection against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflamm

Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J.
Division of Experimental Diabetes and Aging (H.V., W.C., S.G., R.P., A.Y., X.C., L.Z., G.E.S.), Brookdale Department of Adult Development and Geriatrics, Department of Medicine (T.N., G.E.S., J.U.), Division of Nephrology, and Departments of Psychiatry (J.M.S.) and Community and Preventive Medicine (L.T.), Mount Sinai School of Medicine, New York, New York 10029; and National Institute on Aging (L.F.), National Institutes of Health, Bethesda, Maryland 20892.

Context: Increased oxidant stress and inflammation (OS/infl) are linked to both aging-related diseases and advanced glycation end products (AGEs). Whereas AGE receptor-1 (AGER1) reduces OS/infl in animals, this has not been assessed in normal humans. Objective: The objectives of the study were to determine whether AGER1 correlates with AGEs and OS/infl and a reduction of dietary AGEs (dAGEs) lowers OS/infl in healthy adults and chronic kidney disease (CKD-3) patients. Design: This study was cross-sectional with 2-yr follow-up studies of healthy adults and CKD-3 patients, a subset of which received a reduced AGE or regular diet. Setting: The study was conducted at general community and renal clinics. Participants: Participants included 325 healthy adults (18-45 and >60 yr old) and 66 CKD-3 patients. Intervention: An isocaloric low-AGE (30-50% reduction) or regular diet was given to 40 healthy subjects for 4 months and to nine CKD-3 patients for 4 wk. Main Outcome: Relationships between age, dAGEs, serum AGEs, peripheral mononuclear cell AGE-receptors, and OS/Infl before and after reduction of dAGE intake were measured. Results: AGEs, oxidant stress, receptor for AGE, and TNFalpha were reduced in normal and CKD-3 patients after the low-AGE diet, independently of age. AGER1 levels in CKD-3 patients on the low-AGE diet resembled 18- to 45-yr-old normal subjects. Dietary, serum, and urine AGEs correlated positively with peripheral mononuclear cell AGER1 levels in healthy participants. AGER1 was suppressed in CKD-3 subjects, whereas receptor for AGE and TNFalpha were increased. Conclusions: Reduction of AGEs in normal diets may lower oxidant stress/inflammation and restore levels of AGER1, an antioxidant, in healthy and aging subjects and CKD-3 patients. AGE intake has implications for health outcomes and costs and warrants further testing.

Source: J Clin Endocrinol Metab. 2009 Oct 9.

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