Suppression of native defense mechanisms, SIRT1 and PPARγ, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases

Uribarri, Jaime; Cai, Weiping; Pyzik, Renata; Goodman, Susan; Chen, Xue; Zhu, Li; Ramdas, Maya; Striker, Gary E.; Vlassara, Helen

doi:10.1007/s00726-013-1502-4

Cited by 61 publications

(98 citation statements)

References 30 publications

(68 reference statements)

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“…The data extend our previous findings on AGEs promoting the MS in older animals and humans (22)(23)(24). The mouse study further reproduces the cognitive and metabolic conditions recently found to be linked in humans (1,4,5).…”

Section: Discussionsupporting

confidence: 77%

“…Because the MG + mice also manifested in parallel metabolic (22) and cognitive changes, the data may identify MG as a causal link between AD and MS (3,24). Herein, we found a significant temporal decline in cognition in subjects with high baseline sMG level, together with a strong inverse correlation between baseline levels of dietary or serum AGEs and MNC SIRT1 gene levels (24).…”

Section: Discussionmentioning

confidence: 58%

“…At baseline, the cohort's body mass index (BMI) and metabolic and biochemical parameters (n = 93, ≥60 y old, educated, 68% female) were within the range expected for their age, as were calorie and dietary AGE intake (dAGE) (24,26). Baseline cognitive function [by Mini Mental State Examination (MMSE)] was also normal (Table S1).…”

Section: Chronic Mgmentioning

confidence: 98%

“…The MG mouse data further demonstrate that SIRT1 deficiency may be preventable in mice regardless of caloric intake. Changes in the SIRT1 pathway have been linked to AGE receptor levels (22)(23)(24). AGE receptors are expressed in brain neurons, microglia, and endothelium.…”

Section: Discussionmentioning

confidence: 99%

“…Old MG + mice, but not MG − mice, developed age-related MS and kidney and cardiac fibrosis, associated with inflammation and SIRT1 depletion in insulin-sensitive tissues (22). AGE restriction also improved insulin resistance and inflammation in humans (23,24).…”

mentioning

confidence: 99%

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Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Cai

Uribarri²,

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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139

104

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Age-associated dementia and Alzheimer's disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life:, and regular (Reg) chow. Older MG + -fed mice, similar to old Reg controls, developed MS, increased brain amyloid-β 42 , deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPARγ. These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG − mice. The mouse data were enhanced by significant temporal correlations between high circulating AGEs and impaired cognition, as well as insulin sensitivity in older humans, in whom dietary and serum MG levels strongly and inversely associated with SIRT1 gene expression. The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation. Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS.neural | insulin resistance | obesity | nutrition | caloric restriction

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 58%

Section: Chronic Mgmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Cai

Uribarri²,

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

104

View full text Add to dashboard Cite

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Intake of dietary advanced glycation end products influences inflammatory markers, immune phenotypes, and antiradical capacity of healthy elderly in a little‐studied population

Almajwal

Alam

Abulmeaty

et al. 2020

Food Science & Nutrition

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Dietary advanced glycation end products (dAGE) have profound negative effects on overall health, and their intake must be assessed. In this cross‐sectional study, we investigated dAGE intake of 337 adult participants (180/157:M/F; age range 50–73 years). Data were collected on anthropometrics, body composition, dietary intake, selected blood biochemistry, immunological parameters, and antiradical capacity (50% hemolysis time; HT50). From the dietary data, dAGEs and phytochemical index (PI) were calculated. Mean BMI, % body fat (%BF), and fasting plasma glucose were all within the accepted normal range. Subjects with high dAGE intake had higher %BF, higher energy intake, and lower PI. They tended to have lower CD4/CD8 ratios and higher proportions of B cells and NK cells, but had significantly higher hs‐CRP levels and lower HT50 values. Results on HT50 suggested that being >60 years of age enhanced dAGE‐associated impairment of defense capacity in both those with low and high HT50 compared with those <60 years of age. Thus, overall dAGE consumption was high, but elderly participants had lower dAGE intake than younger adults. Indicators of nutritional status and immunological parameters of the subjects were found to be associated with dAGE intake, suggesting a potential impact on health.

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Retracted: Advanced glycation end‐products induce oxidative stress through the Sirt1/Nrf2 axis by interacting with the receptor of AGEs under diabetic conditions

Chen

Zhou

et al. 2018

J of Cellular Biochemistry

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Despite the administration of exogenous insulin and other medications used to control many aspects of diabetes mellitus (DM), increased oxidative stress has been increasingly acknowledged in DM development and complications. Therefore, this study aims to investigate the role of advanced glycation end‐products (AGEs) in oxidative stress (OS) of thyroid cells in patients with DM. Patients with DM with or without thyroid dysfunction (TD) were enrolled. Thyroid toxic damage was induced by adding AGE‐modified bovine serum albumin (AGE‐BSA) to normal human thyroid follicular epithelial cells. The cell viability, cell cycle, and cell apoptosis, as well as the content of reactive oxygen species (ROS), catalase (CAT), and malondialdehyde (MDA) in cells were measured. Thyroid hormones, T3, T4, FT3, and FT4 levels were measured by enzyme‐linked immunosorbent assay. Receptor for advanced glycation end products (RAGE), sirtuin1 ( Sirt1), and NF‐E2‐related factor 2 ( Nrf2) expressions were detected, and the mitochondrial membrane potential was measured. We found increased AGEs in the serum of DM patients with TD. By increasing AGE‐BSA concentration, cell viability; the thyroid hormones T3, T4, FT3, and FT4 levels; and mitochondrial membrane potential all significantly decreased. However, the increase in AGE‐BSA concentration led to an increase in cell apoptosis, RAGE, and nuclear factor‐κB expressions but produced the opposite effect on Sirt1, Nrf2, and heme oxygenase‐1 expressions, as well as a decrease in antioxidant response element protein levels. The AGE‐BSA increased ROS and MDA levels and reduced CAT level in normal human thyroid follicular epithelial cells on a dose independence basis. Our results demonstrated that AGEs‐mediated direct increase of RAGE produced OS in thyroid cells of DM by inactivating the Sirt1/Nrf2 axis.

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Suppression of native defense mechanisms, SIRT1 and PPARγ, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases

Cited by 61 publications

References 30 publications

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Intake of dietary advanced glycation end products influences inflammatory markers, immune phenotypes, and antiradical capacity of healthy elderly in a little‐studied population

Retracted: Advanced glycation end‐products induce oxidative stress through the Sirt1/Nrf2 axis by interacting with the receptor of AGEs under diabetic conditions

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