Oxidative Stress and Advanced Lipoxidation and Glycation End Products (ALEs and AGEs) in Aging and Age-Related Diseases

Abstract

Oxidative stress is a consequence of the use of oxygen in aerobic respiration by living organisms and is denoted as a persistent condition of an imbalance between the generation of reactive oxygen species (ROS) and the ability of the endogenous antioxidant system (AOS) to detoxify them. The oxidative stress theory has been confirmed in many animal studies, which demonstrated that the maintenance of cellular homeostasis and biomolecular stability and integrity is crucial for cellular longevity and successful aging. Mitochondrial dysfunction, impaired protein homeostasis (proteostasis) network, alteration in the activities of transcription factors such as Nrf2 and NF-κB, and disturbances in the protein quality control machinery that includes molecular chaperones, ubiquitin-proteasome system (UPS), and autophagy/lysosome pathway have been observed during aging and age-related chronic diseases. The accumulation of ROS under oxidative stress conditions results in the induction of lipid peroxidation and glycoxidation reactions, which leads to the elevated endogenous production of reactive aldehydes and their derivatives such as glyoxal, methylglyoxal (MG), malonic dialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE) giving rise to advanced lipoxidation and glycation end products (ALEs and AGEs, respectively). Both ALEs and AGEs play key roles in cellular response to oxidative stress stimuli through the regulation of a variety of cell signaling pathways. However, elevated ALE and AGE production leads to protein cross-linking and aggregation resulting in an alteration in cell signaling and functioning which causes cell damage and death. This is implicated in aging and various age-related chronic pathologies such as inflammation, neurodegenerative diseases, atherosclerosis, and vascular complications of diabetes mellitus. In the present review, we discuss experimental data evidencing the impairment in cellular functions caused by AGE/ALE accumulation under oxidative stress conditions. We focused on the implications of ALEs/AGEs in aging and age-related diseases to demonstrate that the identification of cellular dysfunctions involved in disease initiation and progression can serve as a basis for the discovery of relevant therapeutic agents.

Effect of High Glucose-Induced Oxidative Stress on Paraoxonase 2 Expression and Activity in Caco-2 Cells

“…In particular, elevated levels of intracellular AGEs lead to protein cross-linking and aggregation resulting in an alteration in cell signaling, which causes cell damage and death. These alterations are implicated in diabetes and various chronic pathologies [6,20,21].…”

Can advanced glycation end‐products and their receptors be affected by weight loss? A systematic review

“…Individuals with higher body fat have higher caloric and dietary AGE consumption, mainly due to the adoption of a western dietary pattern, rich in simple sugars, saturated fats, and preference for highly processed foods . Moreover, overeating can also promote oxidative stress and as a result increase endogenous AGE formation . Therefore, weight management interventions, such as energy‐restricted diets and bariatric surgery, could play a role in decreasing serum AGE concentrations, both by reducing intake and endogenous formation .…”

Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women

“…Oxidative stress (OS) is a consequence of the use of oxygen in aerobic respiration by living organisms and is characterized as a persistent condition of an imbalance between the generation of ROS and the ability of the endogenous antioxidant system (AOS) to detoxify ROS [4]. The imbalance between pro-oxidants and antioxidants, which may result from diminished levels of antioxidants (AOX) or increased production of ROS [5], leads to tissue damage, lipids, membranes, proteins, and nucleic acids [6].…”

“…The main factors associated with an increase in oxidative stress in menopausal women include obesity, aging, decreased estrogen production, and diet [4,[7][8][9]. Chronic inflammation is a hallmark of aging and obesity and has been implicated in the release of ROS from different sources, including activated macrophages and neutrophils involved in inflammation that generates oxidants, such as peroxynitrite and nitrosoperoxycarbonate, hypohalous acids, and nitrosating agent [7].…”

“…Chronic inflammation is a hallmark of aging and obesity and has been implicated in the release of ROS from different sources, including activated macrophages and neutrophils involved in inflammation that generates oxidants, such as peroxynitrite and nitrosoperoxycarbonate, hypohalous acids, and nitrosating agent [7]. ROS can participate in lipid peroxidation and generate products such as etheno-, propano-, and malondialdehyde that interact with DNA, form DNA adducts, and damage the DNA structure [4,7]. The protective effect of estrogen on oxidative stress is mediated by translocation for specific enzymes from the cytosol that prevent mitochondrial DNA from oxidative attack by free radicals [8].…”