Advanced glycation end-products: a review

Singh, Ravinder; Barden, Anne; Mori, Trevor A.; Beilin, Lawrence J.

doi:10.1007/s001250051591

Cited by 2,216 publications

(1,789 citation statements)

References 109 publications

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“…Chronic accumulation of AGEs is accelerated with aging and with aging‐related diseases such as diabetes, hyperlipidemia, and renal disease (Cho et al ., 2009). Advanced glycation end products AGEs may accumulate in vascular tissues, thickening and stiffening vascular walls, and increasing the risk of hypertension (Singh et al ., 2001; Goh & Cooper, 2008). Higher levels of AGEs are associated with cognitive impairment in people with cerebrovascular disease, suggesting a relationship between AGEs and vascular dementia (Southern et al ., 2007).…”

Section: Introductionmentioning

confidence: 99%

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

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SummaryThere is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

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Section: Introductionmentioning

confidence: 99%

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

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“…Glycation is the reaction of carbonyl compounds, including glucose, ascorbate oxidation products, and methylglyoxal, that forms a variety of structurally diverse stable adducts in proteins; these adducts are collectively known as advanced glycation endproducts or AGEs (Singh et al ., 2001). Several studies have shown the accumulation of AGEs in the aged BM of the kidneys, lungs, and lens capsule (Bailey et al ., 1993; Oldfield et al ., 2001; Song et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

et al. 2016

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SummaryProteins in basement membrane (BM) are long‐lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial‐to‐mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age‐dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC‐MS/MS. The TGFβ2‐mediated upregulation of the mRNA levels (by qPCR) of EMT‐associated proteins was significantly enhanced in cells cultured on AGE‐modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGFβ1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFβ2‐mediated α‐smooth muscle actin (αSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFβ2‐mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes‐associated fibrosis.

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“…Advanced glycation endproducts form when glucose reacts with the proteins to form unstable Schiff bases, which then undergo further modification to form Amadori products (44,50). Additional rearrangements or modifications may occur giving rise to advanced glycation endproducts seen in prolonged hyperglycemia or aged individuals.…”

Section: Introductionmentioning

confidence: 99%

“…AGEs have been shown to be etiologic factors in diabetes-induced nephropathy, retinopathy, neuropathy, and diabetes-accelerated atherosclerosis (40,44,50). AGEs are also thought to contribute to many of the complications of aging including disorders such as osteoarthritis, cataract formation and changes observed in myocardial dysfunction (6,30,39).…”

Section: Introductionmentioning

confidence: 99%

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

Alikhani

Boyd

et al. 2007

Bone

321

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We have previously shown that diabetes significantly enhances apoptosis of osteoblastic cells in vivo and that the enhanced apoptosis contributes to diabetes impaired new bone formation. A potential mechanism is enhanced apoptosis stimulated by advanced glycation endproducts (AGEs). To investigate this further, an advanced glycation product, carboxymethyl lysine modified collagen (CML-collagen) was injected in vivo and stimulated a 5 fold increase in calvarial periosteal cell apoptosis compared to unmodified collagen. It also induced apoptosis in primary cultures of human or neonatal rat osteoblastic cells or MC-3T3-E1 cells in vitro. Moreover, the apoptotic effect was largely mediated through RAGE receptor. CML-collagen increased p38 and JNK activity 3.2 and 4.4 fold, respectively. Inhibition of p38 and JNK reduced CML-collagen stimulated apoptosis by 45% and 59% and by 90% when used together (P<0.05). The predominant apoptotic pathway induced by CML-collagen involved caspase-8 activation of caspase-3 and was independent of NF-κB activation. When osteoblastic cells were exposed to a long-term low dose incubation with CMLcollagen there was a higher degree of apoptosis compared to short term incubation. In more differentiated osteoblastic cultures apoptosis was enhanced even further. These results indicate that advanced glycation endproducts, which accumulate in diabetic and aged individuals may promote apoptosis of osteoblastic cells and contribute to deficient bone formation.

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Advanced glycation end-products: a review

Cited by 2,216 publications

References 109 publications

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

AGEs in human lens capsule promote the TGFβ2‐mediated EMT of lens epithelial cells: implications for age‐associated fibrosis

Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways

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