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

Protection Against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflammatory AGE receptor-1

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Free PMC article

Protection Against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflammatory AGE receptor-1

Helen Vlassara et al. J Clin Endocrinol Metab. .
Free PMC article

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.

Figures

Figure 1
Figure 1
A, Associations between serum CML, shown in AGE (units per milliliter), and age (n = 194). Extreme tertiles for dietary AGEs in young (<45 yr old) are compared with all healthy subjects older than 60 yr for sCML (B), sMG (C), PMNC AGER1 mRNA (D), and serum hsCRP (E) (n = 20/subgroup). Data are shown as means ± sem. *, P < 0.05 between lowest and highest dietary AGE tertile in healthy participants younger than 45 yr; **, P < 0.05 between lowest dietary tertile in the subjects 18–45 yr old and all subjects older than 60 yr.
Figure 2
Figure 2
Temporal correlations of changes of circulating AGEs (CML) with changes of oxidant marker 8-isoprostanes (A), PMNC-derived TNF-α (B), VCAM-1 (C), and dietary AGE intake (D). Healthy participants (n = 49) were followed up for 2 yr while on their habitual diet. Statistical significance is indicated.
Figure 3
Figure 3
PMNC AGER1 mRNA expression in healthy subjects (n = 111) correlates with serum CML (A) and serum MG (B) but not in patients with CKD (n = 66) (C and D). Data are shown in human AGER1 gene copy numbers per cell by RT-PCR, CML (units per milliliter) and MG (nanomoles per milliliter) of fasting serum.
Figure 4
Figure 4
Relative PMNC protein expression levels of AGER1 (A), RAGE (B), and p66shc (C) in healthy 18- to 45-yr-old subjects, subjects older than 60 yr, and CKD patients. Freshly isolated PMNCs were used for Western analysis. Density data are shown as means ± sem. Western blots are representative of five subjects per group, each performed three times. *, P < 0.05; **, P < 0.01.
Figure 5
Figure 5
A, Effects of a low-AGE dietary intervention on oxidant stress, inflammation, serum AGEs, and PMNC AGE in healthy subjects. Healthy subjects (n = 30) were randomly assigned to a regular diet or an isocaloric diet containing 50% lower AGEs for 4 months. *, P < 0.05. B, Effects of a low-AGE dietary intervention on OS, inflammation, serum AGEs, and PMNC AGE in CKD patients. CKD patients (n = 9) were randomly assigned to the low-AGE diet for 4 wk. *, P < 0.05.

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