Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE receptor-1

J Clin Endocrinol Metab. 2009 Nov;94(11):4483-91. doi: 10.1210/jc.2009-0089. Epub 2009 Oct 9.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / physiology*
  • Blood Glucose / metabolism
  • Blood Pressure
  • Body Mass Index
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Creatinine / metabolism
  • Cross-Sectional Studies
  • Glycation End Products, Advanced / administration & dosage*
  • Humans
  • Inflammation / physiopathology
  • Kidney Diseases / genetics
  • Kidney Diseases / physiopathology*
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / physiopathology*
  • Middle Aged
  • Neutrophils / physiology
  • Polymerase Chain Reaction
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics*
  • Receptors, Immunologic / physiology
  • Reference Values
  • Young Adult

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycation End Products, Advanced
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Creatinine