Effects Of Extracellular Matrix Stiffness On Muscle Fiber Mechanotransduction Signaling In Aged Rats

Abstract

The loss of muscle mass with age, termed sarcopenia, is a common problem among the over 60 years-old population. Resistance training is often prescribed as treatment, but older adults have shown a reduced response to exercise. Muscle stiffness is shown to increase with age due to increased glycation. Increased stiffness will cause muscle cells to experience less strain for any given load. Strain is known to be the mechanical signal for a muscle's response to exercise, which leads us to hypothesize that response to exercise is impaired because of increased stiffness. Nineteen rats were split into young (12 months) and old (32-33 months) groups. Each rat underwent 3 sets of 10 maximum eccentric dorsiflexions. Following sacrifice, the tibialis anterior (TA) of both legs and extensor digitorum longus (EDL) of the non-exercised leg harvested. The EDL underwent stiffness testing to determine the Young's modulus of the muscle. Focal adhesison kinase (FAK) is a protein that is phosphorylated with stretch, making it a good indicator of exercise response. The TAs were used in immunoblotting analysis to determine the ratio of FAK that was phosphorylated. Our study showed decreases in muscle size and increases in muscle stiffness with age, with more variability occurring in older rats. A negative relationship was also seen between muscle stiffness and size. The main findings of our study showed that FAK activity decreases are related to muscle stiffness. The results of this study show that aging is similar between rats and humans, in regards to muscle size and stiffness, and suggest sarcopenic muscle is stiffer than healthy muscle. The results also suggest old muscle loses the capacity to hypertrophy in response to exercise and that increased muscle stiffness is responsible for the decreased response to exercise. This study implicates that reduced response to exercise due to increased muscle stiffness is a possible mechanism behind the development of sarcopenia.