Aged tissues are characterized by increased levels of oxidative stress, meaning the generation and presence of more oxidizing molecules than cells can comfortably handle. A major source of oxidizing molecules is the activity of mitochondria, and an increase in this production of oxidizing molecules is one of the reasons why mitochondrial dysfunction is important in aging. Oxidative reactions damage molecular machinery in the cell, impairing function. Lipid molecules are particularly vulnerable to oxidation that produces damaging consequences. To cope with this, cells can either more aggressively repair that damage or more aggressively produce antioxidants, but there are limits to the degree to which these approaches can compensate.
Lipid peroxidation involves a series of chemical reactions in which lipid molecules, particularly polyunsaturated fatty acids (PUFAs), are oxidatively attacked by free radicals or non-radical species in the cell membrane or intracellular structures. This process generates lipid radicals and peroxides, which damage the cell membrane structure and function, triggering a chain reaction that further impairs cellular function and induces apoptosis.
Cells have endogenous defense mechanisms to counteract this oxidative damage. The main defense mechanisms include antioxidant enzyme systems (such as superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic antioxidants (such as glutathione, vitamin E, and vitamin C). These mechanisms protect cells from oxidative damage by scavenging reactive oxygen species (ROS) and neutralizing lipid peroxidation products. However, under aging or chronic disease conditions, these endogenous defense mechanisms may be impaired, leading to elevated lipid peroxidation levels and exacerbating cellular damage, potentially contributing to diseases such as muscle atrophy.
In sarcopenia, lipid peroxidation may impact muscle health through several pathways. Firstly, lipid peroxidation products directly damage muscle cell membranes, leading to apoptosis and muscle loss. Secondly, lipid peroxidation products can induce inflammation and oxidative stress, further exacerbating muscle damage. Additionally, lipid peroxidation influences sarcopenia through various mechanisms, including metabolic disorders, ferroptosis, mitochondrial dysfunction, autophagy and apoptosis, extracellular matrix remodeling, cell signaling pathways, as well as lifestyle and nutritional factors. This review summarizes the current research on lipid peroxidation and sarcopenia, including the molecular mechanisms by which lipid peroxidation influences muscle atrophy, protective mechanisms that reduce lipid peroxidation in slowing sarcopenia progression, and lipid peroxidation-based therapeutic strategies for sarcopenia.
Link: https://doi.org/10.3389/fmed.2025.1525205
View the full article at FightAging
