Effects of 18-month treatment with bazedoxifene on enzymatic immature and mature cross-links and non-enzymatic advanced glycation end products, mineralization, and trabecular microarchitecture of vertebra in ovariectomized monkeys

The renal accumulation of advanced glycation end products (AGEs) is a causative factor of various renal diseases, including chronic kidney disease and diabetic nephropathy. AGE inhibitors, such as aminoguanidine and pyridoxamine, have the therapeutic activities for reversing the increase in renal AGE burden. This study evaluated the inhibitory effects of ethyl pyruvate (EP) on methylglyoxal- (MGO-) modified AGE cross-links with proteins in vitro. We also determined the potential activity of EP in reducing the renal AGE burden in exogenously MGO-injected rats. EP inhibited MGO-modified AGE-bovine serum albumin (BSA) cross-links to collagen (IC50=0.19±0.03 mM) in a dose-dependent manner, and its activity was stronger than aminoguanidine (IC50=35.97±0.85 mM). In addition, EP directly trapped MGO (IC50=4.41±0.08 mM) in vitro. In exogenous MGO-injected rats, EP suppressed AGE burden and MGO-induced oxidative injury in renal tissues. These activities of EP on the MGO-mediated AGEs cross-links with protein in vitro and in vivo showed its pharmacological potential for inhibiting AGE-induced renal diseases.

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Advanced Glycation End Products Play Adverse Proinflammatory Activities in Osteoporosis

Mediators of Inflammation ◽

10.1155/2014/975872 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 38

Author(s):

Roberta Sanguineti ◽

Alessandra Puddu ◽

François Mach ◽

Fabrizio Montecucco ◽

Giorgio Luciano Viviani

Keyword(s):

Advanced Glycation End Products ◽

Molecular Mechanisms ◽

Systemic Circulation ◽

Advanced Glycation ◽

Public Health Burden ◽

Glycation End Products ◽

End Products ◽

Cross Links ◽

High Level ◽

Global Population

Osteoporosis is a major public health burden that is expected to further increase as the global population ages. In the last twenty years, advanced glycation end products (AGEs) have been shown to be critical mediators both in the pathogenesis and development of osteoporosis and other chronic degenerative diseases related to aging. The accumulation of AGEs within the bone induces the formation of covalent cross-links with collagen and other bone proteins which affects the mechanical properties of tissue and disturbs bone remodelling and deterioration, underlying osteoporosis. On the other hand, the gradual deterioration of the immune system during aging (defined as immunosenescence) is also characterized by the generation of a high level of oxidants and AGEs. The synthesis and accumulation of AGEs (both localized within the bone or in the systemic circulation) might trigger a vicious circle (in which inflammation and aging merged in the word “Inflammaging”) which can establish and sustain the development of osteoporosis. This narrative review will update the molecular mechanisms/pathways by which AGEs induce the functional and structural bone impairment typical of osteoporosis.

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Advanced Glycation End-products (AGEs): An emerging concern for processed food industries

10.31219/osf.io/497rt ◽

2020 ◽

Author(s):

Chetan Sharma

Keyword(s):

Advanced Glycation End Products ◽

Biological Effects ◽

Cross Linking ◽

Processed Foods ◽

Processed Food ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Cross Links ◽

Microvascular And Macrovascular Complications

The global food industry is expected to increase more than US $ 7 trillion by 2014. This rise in processed food sector shows that more and more people are diverging towards modern processed foods. As modern diets are largely heat processed, they are more prone to contain high levels of advanced glycation end products (AGEs). AGEs are a group of complex and heterogeneous compounds which are known as brown and fluorescent cross-linking substances such as pentosidine, non-fluorescent cross-linking products such as methylglyoxal-lysine dimers (MOLD), or non-fluorescent, non-cross linking adducts such as carboxymethyllysine (CML) and pyrraline (a pyrrole aldehyde). Animal derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. Most studies on the biological effects of AGEs have been carried out by administering heated processed foods. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE).The chemistry of AGE formation and their patho-biochemistry particularly in relation to the diabetic complications as well as their relation role in the aging discussed. The emerging evidence about the adverse effects of AGEs makes it necessary to investigate the different therapies to inhibit AGEs.

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Advanced Glycation End Products Are Retained in Decellularized Muscle Matrix Derived from Aged Skeletal Muscle

International Journal of Molecular Sciences ◽

10.3390/ijms22168832 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8832

Author(s):

Lucas C. Olson ◽

Tri M. Nguyen ◽

Rebecca L. Heise ◽

Barbara D. Boyan ◽

Zvi Schwartz ◽

...

Keyword(s):

Skeletal Muscle ◽

Advanced Glycation End Products ◽

Cross Linking ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Age Dependent ◽

Before And After ◽

The Matrix ◽

Cross Links

Decellularized tissues are biocompatible materials that engraft well, but the age of their source has not been explored for clinical translation. Advanced glycation end products (AGEs) are chemical cross-links that accrue on skeletal muscle collagen in old age, stiffening the matrix and increasing inflammation. Whether decellularized biomaterials derived from aged muscle would suffer from increased AGE collagen cross-links is unknown. We characterized gastrocnemii of 1-, 2-, and 20-month-old C57BL/6J mice before and after decellularization to determine age-dependent changes to collagen stiffness and AGE cross-linking. Total and soluble collagen was measured to assess if age-dependent increases in collagen and cross-linking persisted in decellularized muscle matrix (DMM). Stiffness of aged DMM was determined using atomic force microscopy. AGE levels and the effect of an AGE cross-link breaker, ALT-711, were tested in DMM samples. Our results show that age-dependent increases in collagen amount, cross-linking, and general stiffness were observed in DMM. Notably, we measured increased AGE-specific cross-links within old muscle, and observed that old DMM retained AGE cross-links using ALT-711 to reduce AGE levels. In conclusion, deleterious age-dependent modifications to collagen are present in DMM from old muscle, implying that age matters when sourcing skeletal muscle extracellular matrix as a biomaterial.

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