Effects of Prolonged Dietary Curcumin Exposure on Skeletal Muscle Biochemical and Functional Responses of Aged Male Rats
Sarcopenia, an age-related condition involving the decline of muscle mass and function, affects 11-50% of those 80 years and older. The causes of sarcopenia are complex as the process of aging is characterized by several biological events. Skeletal muscle oxidative stress is one example and can result in disrupted cellular redox regulation and altered transcription factor activity. In this paper, the authors focus on characterizing the effects of curcumin, a compound shown to combat oxidative damage-inducing agents in aging skeletal muscle. As such, this study analyzed muscle mass and function in aged F344xBN rats exposed to long-term dietary curcumin. Rats were divided into three groups, one of which was provided a curcumin supplemented diet (CUR), the second consisting of rats given a modified amount of food to match the food consumption of CUR rats (PAIR), and a control group consuming a standard diet (CON). After four months of dietary supplementation, functional assessment of the rat plantaris muscle was assessed in situ. Contractile characteristics were measured isometrically at optimal length to determine maximum twitch and tetanic tension using the 1305A 3-in-1 Whole Animal System. The authors found that plantaris muscle mass and peak tetanic tension was significantly greater in CUR mice when compared to PAIR mice. Furthermore, both CON and CUR mice had significantly greater plantaris peak twitch tension than PAIR mice. In addition to this, molecular analysis showed that CUR mice exhibited greater levels of nuclear nrf2 and lower levels of oxidative damage markers when compared to PAIR mice. These differences in expression may mediate the increased peak twitch tension and peak tetanic tension seen in CUR mice, as oxidative stress can cause muscle contractile dysfunction and thus decreased force. In a complimentary study, CUR mice exhibited a greater peak twitch and specific tetanic tension response of the plantaris when administered curcumin via osmotic pumps. Taken together, these findings may help in elucidating the effectiveness of long-term curcumin supplementation in treating sarcopenia.
Specific inhibition of myostatin activation is beneficial in mouse models of SMA therapy
Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in the Survival of Motor Neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein. The disease is characterized by the loss of α-motor neurons, which can lead to skeletal muscle atrophy, reduced bone mineral density, and increased risk of fracture. SMN restoration treatment has been found to improve functional symptoms, although not in full. This study investigates the combined effect of SMN treatment with inhibition of myostatin activation in SMA mice models. Three mice models exhibiting varying severities of SMA were analyzed, including low, low-high, and high-dose SMN restored mice. In order to prevent myostatin activation, mice were treated with muSRK-015P. Mice treated with muSRK-015P exhibited increased gastrocnemius and tibialis anterior (TA) muscle mass. Functional assessment of the plantarflexor muscle group was then conducted using Aurora’s 1300A 3-in-1 Whole Animal System. Although untreated low-high and high dose mice displayed reduced maximal torque, those treated with muSRK-015P showed improvements in maximal torque measurements. To investigate whether the inhibition of myostatin activation could reduce bone deficiencies, mice underwent μCT imaging of the tibias following muSRK-015P treatment. Inhibition of myostatin activation in high dose mice resulted in increased cross-sectional bone area and bone volume. Bone volume and trabecular separation improvements were seen across all mice treated with muSRK-015P. The authors then quantified pre-existing latent myostatin concentrations in WT and SMN-restored mice. Although reduced concentrations were found in low-high dose mice when compared to WT, no differences were observed following normalization to body weight. This suggests that reduced levels of latent myostatin seen in more severe SMA disease models is a result of decreased muscle mass, rather than an upstream cause of which. These data suggest that the inhibition of myostatin activation, especially when combined with SMN restoration, may serve as a beneficial therapeutic treatment for SMA patients.