Advanced glycation endproducts (AGEs) are an undesirable form of metabolic waste. The formation of long-lived AGEs that cross-link molecules in the extracellular matrix can change the physical properties of tissue, such as by contributing to the stiffening of blood vessel walls that occurs with age. Further, most varieties of AGE, while being only short-lived, can interact with cell receptors to provoke a maladaptive inflammatory response, thereby contributing to the chronic inflammation of aging. Inflammation, in turn, alters cell behavior for the worse throughout the body. Here, researchers provide an overview of how AGEs contribute to the age-related loss of muscle mass that leads to sarcopenia.
By binding with receptor for advanced glycation end products (RAGEs), AGEs can activate a series of intracellular signalling pathways in skeletal muscle cells related to the elevated levels of inflammation and oxidative stress, as well as impaired insulin/insulin-like growth factor-1 (IGF-1) signalling and mitochondrial biogenesis, which lead to reduced protein synthesis, increased protein degradation, intracellular lipid accumulation, changes in muscle fibre type composition and muscle energy metabolism, and a higher rate of apoptosis, finally resulting in muscle atrophy and impaired regeneration abilities.
Through directly targeted glycosylation, AGEs can damage the biological properties and functions of proteins which include the functional and structural proteins of skeletal muscle as well as collagens in the extracellular matrix, resulting in muscle dysfunction such as impaired force production and increased stiffness. Furthermore, AGEs can also indirectly affect skeletal muscle by contributing to neuromuscular junction lesion and vascular disorders.
Link: https://doi.org/10.1...JR-2024-0252.R1
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