Oxidative stress and aging: is methylglyoxal the hidden enemy?
Aging is a multifactorial process that involves changes at the cellular, tissue, organ and the whole body levels resulting in decreased functioning, development of diseases, and ultimately death. Oxidative stress is believed to be a very important factor in causing aging and age-related diseases. Oxidative stress is caused by an imbalance between oxidants such as reactive oxygen species (ROS) and antioxidants. ROS are produced from the mitochondrial electron transport chain and many oxidative reactions. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite formed during glucose, protein and fatty acid metabolism. MG levels are elevated in hyperglycemia and other conditions. An excess of MG formation can increase ROS production and cause oxidative stress. MG reacts with proteins, DNA and other biomolecules, and is a major precursor of advanced glycation end products (AGEs). AGEs are also associated with the aging process and age-related diseases such as cardiovascular complications of diabetes, neurodegenerative diseases and connective tissue disorders. AGEs also increase oxidative stress. In this review we discuss the potential role of MG in the aging process through increasing oxidative stress besides causing AGEs formation. Specific and effective scavengers and crosslink breakers of MG and AGEs are being developed and can become potential treatments to slow the aging process and prevent many diseases.
Desai
Kaushik M
KM
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Chang
Tuanjie
T
Wang
Hui
H
Banigesh
Ali
A
Dhar
Arti
A
Liu
Jianghai
J
Untereiner
Ashley
A
Wu
Lingyun
L
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000096:biosynthesis; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011765:Pyruvaldehyde / Q000009:adverse effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde