Establishing In Vitro 3D Sarcopenia Model Using Skeletal Muscle-on-a-Chip

Abstract

Sarcopenia, the progressive loss of muscle mass that occurs with aging, leads to impaired movement, increased risk of injury, and reduced quality of life. The pathogenic roles of advanced glycation end-products (AGEs) in skeletal muscle have been reported, but practical experiments to assess the impact of AGEs on skeletal muscle from a mechanical standpoint are lacking. To address this issue, we have developed a skeletal muscle-on-a-chip system that generates 3D skeletal muscle tissue and measures muscular morphology and contractile function. Using this system, we investigate the impact of AGEs on skeletal muscle for the first time, demonstrating their damaging effects on contractile function, myotube degeneration, and cell death in skeletal muscle tissue. Our results are confirmed through various methods, including contraction force measurement, biochemical assays, Next Generation Sequencing (NGS), and Fluorescence-lifetime imaging microscopy (FLIM). This study provides a 3D in vitro sarcopenia model using an organ-on-a-chip system, which enables the investigation of the impact of AGEs on skeletal muscle. Our approach offers a new perspective on sarcopenia and provides a platform for investigating other substances as well.