Insights Into the Pathways Involved in Muscle Aging
Muscle aging has several underlying factors, including decreased numbers of muscle stem cells, mitochondrial dysfunction, a decline in protein quality and turnover, and hormonal deregulation. Loss of muscle mass is associated with—and possibly preceded by—muscle weakness, which can make carrying out daily activities difficult for seniors. This can lead to further inactivity, which itself leads to further muscle loss. A comprehensive understanding of cellular and molecular pathways involved in muscle aging could lead to the development of therapeutic interventions to boost protein synthesis and increase muscle mass. Advancements in nutrition and inflammation research can be seen in the following two publications that describe signalling pathways and dietary nitrate supplements to help reduce muscle dysfunction associated with age.
Dietary nitrate supplementation increases diaphragm peak power in old mice
This publication, by Kumar et al. (2020), investigates the mechanisms of dietary nitrate effects on contractile function of inspiratory muscles in mice. They hypothesized that dietary nitrate supplementation would enhance diaphragm contractile function in old mice. To test this hypothesis, they surgically isolated a diaphragm muscle strip with portions of the rib and central tendon attached. The rib was tied to a glass rod and the central tendon was attached to our 300C-LR Dual-Mode Muscle Lever. These experiments showed that old mice receiving dietary inorganic nitrate supplements displayed greater diaphragm peak power and maximal rate of force development during tetanic contractions. Previous measurements of peak power in young mice compared to peak power measured in old mice suggest that moderate ageing causes a 30–40% decline in diaphragm peak power, and that 14 days of dietary nitrate supplementation restores peak power to ‘near-normal’ (young) values. Dietary nitrate may thus increase maximal inspiratory muscle ‘power’, which may be relevant to improve the non-ventilatory function of the diaphragm in elderly human patients.
Inhibition of inflammatory CCR2 signaling promotes aged muscle regeneration and strength recovery after injury
Blanc, et al. (2020) examined the inflammatory pathway associated with muscle injury and regeneration in aged mice. Muscle force generation capacity was analyzed in extensor digitorum longus (EDL) muscles using our 1200A Isolated Muscle System. They found that inflammatory chemokine receptors were expressed in non-hematopoietic myogenic progenitor cells during regeneration post-injury. Timely inhibition of these receptors stimulated aged muscle regeneration and functional recovery after an acute injury. These results demonstrate that inflammatory-induced activation of chemokine receptor signaling in myogenic cells contributes to regenerative decline in aged muscles. This inhibition-based therapy could be used to restore tissue regeneration or improve cell-based therapies in aged and inflamed tissues. This study gives us further insight into the systemic effects of chemokine receptor inhibition and helps to guide the development of future clinical therapeutic strategies for aged tissue regeneration.