Reduced oxidant stress and extended lifespan in mice exposed to a low glycotoxin diet: association with increased AGER1 expression.
Aging is accompanied by increased oxidative stress (OS) and accumulation of advanced glycation end products (AGEs). AGE formation in food is temperature-regulated, and ingestion of nutrients prepared with excess heat promotes AGE formation, OS, and cardiovascular disease in mice. We hypothesized that sustained exposure to the high levels of pro-oxidant AGEs in normal diets (Reg(AGE)) contributes to aging via an increased AGE load, which causes AGER1 dysregulation and depletion of anti-oxidant capacity, and that an isocaloric, but AGE-restricted (by 50%) diet (Low(AGE)), would decrease these abnormalities. C57BL6 male mice with a life-long exposure to a Low(AGE) diet had higher than baseline levels of tissue AGER1 and glutathione/oxidized glutathione and reduced plasma 8-isoprostanes and tissue RAGE and p66(shc) levels compared with mice pair-fed the regular (Reg(AGE)) diet. This was associated with a reduction in systemic AGE accumulation and amelioration of insulin resistance, albuminuria, and glomerulosclerosis. Moreover, lifespan was extended in Low(AGE) mice, compared with Reg(AGE) mice. Thus, OS-dependent metabolic and end organ dysfunction of aging may result from life-long exposure to high levels of glycoxidants that exceed AGER1 and anti-oxidant reserve capacity. A reduced AGE diet preserved these innate defenses, resulting in decreased tissue damage and a longer lifespan in mice.
Cai
Weijing
W
Mount Sinai School of Medicine, Box 1640, One Gustave Levy Place, New York, NY 10029, USA.
He
John Cijiang
JC
Zhu
Li
L
Chen
Xue
X
Wallenstein
Sylvan
S
Striker
Gary E
GE
Vlassara
Helen
H
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D004032:Diet; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004435:Eating; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008017:Life Expectancy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D024141:Collagen Type IV; D017127:Glycation End Products, Advanced; D007328:Insulin; D016877:Oxidants; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D053773:Transforming Growth Factor beta1; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D005978:Glutathione; D005947:Glucose