Detrimental effects of advanced glycation end-products (AGEs) on a 3D skeletal muscle model in microphysiological system

Abstract

Skeletal muscle is essential for maintaining body shape and supporting physiological processes. Musculoskeletal function is influenced by various factors, including nutrition, infection, injury or trauma, and advanced glycation end-products (AGEs), which are known to contribute in tissue degeneration, particularly in aging and diabetic populations. This study utilized a skeletal muscle-on-a-chip system to develop three-dimensional in vitro musculoskeletal tissue, enabling a detailed investigation of the effects of AGEs on muscle function and structure. AGEs-induced alterations on muscle were verified by assessments of musculoskeletal contractility, myotube growth, and apoptosis markers. Furthermore, metabolic changes such as modifications in collagen and NADH lifetime changes were observed using fluorescence-lifetime imaging microscopy (FLIM) in the AGEs-treated group. Our result demonstrated a significant reduction in musculoskeletal contractility and structural disruptions in response to AGEs exposure. Overall, these findings provide a robust in vitro model for elucidating the mechanisms by which AGEs impair muscle functionality and integrity, with potential implications for therapeutic strategies aimed at preserving muscle health and enhancing the quality of life in affected populations.

Keywords: Advanced glycation end-products; Extracellular matrix alterations; Fluorescence-lifetime imaging microscopy; Musculoskeletal function; Skeletal muscle-on-a-chip.