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


METHODS
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.


METHODS
The study was conducted at general community and renal clinics.


METHODS
Participants included 325 healthy adults (18-45 and >60 yr old) and 66 CKD-3 patients.


METHODS
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.


RESULTS
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.
Vlassara
Helen
H
Division of Experimental Diabetes and Aging, Mount Sinai School of Medicine, New York, New York 10029, USA. helen.vlassara@mssm.edu
Cai
Weijing
W
Goodman
Susan
S
Pyzik
Renata
R
Yong
Angie
A
Chen
Xue
X
Zhu
Li
L
Neade
Tina
T
Beeri
Michal
M
Silverman
Jeremy M
JM
Ferrucci
Luigi
L
Tansman
Laurie
L
Striker
Gary E
GE
Uribarri
Jaime
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D017127:Glycation End Products, Advanced / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007674:Kidney Diseases / Q000235:genetics / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000503:physiopathology*; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D016133:Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics* / Q000502:physiology; D012016:Reference Values; D055815:Young Adult
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D003404:Creatinine