Role of advanced glycation end products in cellular signaling
Open accessAbstract
Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.
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AGEs can interact with other cell surface receptors, including AGE-R1, AGE-R2, AGE-R3, and scavenger receptors, that possess the opposite function of RAGEs.
“These AGE cell surface receptors include AGE-R1, AGE-R2, AGE-R3, and scavenger receptors such as macrophage scavenger receptors, scavenger receptor class B type I and II (SR-BI, SR-BII), and cluster of differentiation 36 (CD36).”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [46]
Interaction of AGEs with these receptors can enhance their catabolism and clearance by modulating endocytosis and degradation, suggesting a potentially adaptive defensive mechanism.
“The interaction of AGEs with these receptors can enhance their catabolism and clearance by modulating endocytosis and degradation45,46, suggesting a potentially adaptive defensive mechanism in the body to reduce the detrimental effects of increased glycation products.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [46]
Conditions including aging, diabetes, renal failure, tobacco smoking, and excessive alcohol consumption that induce AGE accumulation and AGE-RAGE interaction are risk factors for increased bone fracture and osteoporosis.
“Notably, several conditions, including aging, diabetes, renal failure, tobacco smoking, and excessive alcohol consumption that induce AGE accumulation and AGE-RAGE interaction, are risk factors for increased bone fracture and osteoporosis46,85.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [46]
Sugar moiety-related protein adduct such as advanced glycation end products (AGEs) can be produced by high fat or excessive alcohol exposure or under pathological states such as diabetes, cardiovascular diseases and Alzheimer's disease.
“In addition to lipid peroxide-related protein adducts, recent data suggest that sugar moiety-related protein adduct such as advanced glycation end products (AGEs) can be produced by high fat or excessive alcohol exposure or under pathological states such as diabetes, cardiovascular diseases and Alzheimer's disease, as recently reviewed [190], [191], [192], [193].”
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- Authors
- Ott, C., Jacobs, K., Haucke, E., Navarrete Santos, A., Grune, T., & Simm, A.
- Affiliations
- Friedrich Schiller University Jena (DE)
- University Hospital in Halle (DE)
- Martin Luther University Halle-Wittenberg (DE)
- Corresponding author
- Simm, Andreas
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2014
- Volume
- 2
- Pages
- 411-429
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC3949097
- OpenAlex
- W2086327676
- Cited by
- 1,150
- References
- 233
- Citations by year
- 2026: 62 · 2025: 82 · 2024: 105 · 2023: 121 · 2022: 108 · 2021: 131 · 2020: 107 · 2019: 106 · 2018: 86 · 2017: 94 · 2016: 70 · 2015: 52 · 2014: 21 · 2012: 1
- FWCI
- 10.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- advanced glycation end products, AGE receptor, signal transduction, protein modification, inflammatory signaling, age-related diseases, neurodegeneration, cardiovascular disease, arteriosclerosis, frailty, dietary AGEs
- MeSH terms
- Receptor for Advanced Glycation End Products, Aging, Animals, Bone and Bones, Dietary Proteins, Humans, Hyperglycemia, Immune System, Inflammation, Lung, Models, Biological, Neurons, Polymers, Receptors, Immunologic, Lipid Peroxidation, Signal Transduction, Maillard Reaction, NF-kappa B, Glycation End Products, Advanced, Reactive Oxygen Species, Oxidative Stress, Protein Transport, Reactive Nitrogen Species, Receptors, Scavenger, Protein Aggregates
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