SA1: To characterize the impact of circadian disturbance and partial gravity in a lunar analog in male and female rats. 60 adult outbred rats (30/sex) will undergo 7 days of exposure to partial weight-bearing at 20% of normal loading (PWB20) to simulate lunar gravity. 1 group will be exposed to a regular light cycle (LD), 1 group will be kept in constant light to induce circadian free-running (LL), and the experimental group will be exposed to CJL using a 6h phase advance every other day.

SA2: To determine and compare the long-term effects of circadian disturbance and altered gravity during muscle recovery in males and females. 20 animals (10/sex) will be exposed to the same PWB20+CJL paradigm as in Aim 1. Animals will be allowed to recover for 7 days at normal loading (1g) and under a standard light cycle (LD).

For this work, I plan on first assessing muscle health and function through regular testing including grip strength, fatigue resistance, force production, and muscle quality. I will also monitor circadian parameters and rest/activity over several 24h periods. Finally, I will perform biomolecular assays in the suprachiasmatic nucleus and soleus muscle, targeting specific genes involved in circadian rhythm entrainment, muscle function, and inflammation.

This promising pilot study will help assess the additive effects of circadian disturbance in animals exposed to partial gravity and will help determine the existence of sex-based differences in response to spaceflight stressors. Moreover, I will determine sex-based differences during muscle recovery following disuse, and the long-term impact of circadian disturbance on muscle health and function. This study, which includes phenotypical and molecular outcomes, will assess the contribution of muscle clock genes and pathways to muscle health. Finally, targeted molecular assessment will help me use my diverse background (metabolism, neuromuscular, circadian) to explore other systems of interest that may be linked to muscle health and function (e.g., metabolic signaling pathways), and help characterize the key players that could be targeted with pharmacological approaches to provide new and effective countermeasures in future studies.

We previously reported notable sex differences in young adult rats where, when exposed to mechanical unloading, females had a better ability to maintain musculoskeletal health than males. In our study, using 6 month old outbred animals coming from a different strain and under regular light cycles, we have replicated these findings. We also were able to detect notable differences regarding several circadian output parameters such as body temperature and grip strength.

Our experiments in disturbed light conditions are currently ongoing.

SA1: To characterize the impact of circadian disturbance and partial gravity in a lunar analog in male and female rats. 60 adult outbred rats (30/sex) will undergo 7 days of exposure to partial weight-bearing at 20% of normal loading (PWB20) to simulate lunar gravity. 1 group will be exposed to a regular light cycle (LD), 1 group will be kept in constant light to induce circadian free-running (LL), and the experimental group will be exposed to CJL using a 6h phase advance every other day.

SA2: To determine and compare the long-term effects of circadian disturbance and altered gravity during muscle recovery in males and females. 20 animals (10/sex) will be exposed to the same PWB20+CJL paradigm as in Aim 1. Animals will be allowed to recover for 7 days at normal loading (1g) and under a standard light cycle (LD).

For this work, I plan on first assessing muscle health and function through regular testing including grip strength, fatigue resistance, force production, and muscle quality. I will also monitor circadian parameters and rest/activity over several 24h periods. Finally, I will perform biomolecular assays in the suprachiasmatic nucleus and soleus muscle, targeting specific genes involved in circadian rhythm entrainment, muscle function, and inflammation.

This promising pilot study will help assess the additive effects of circadian disturbance in animals exposed to partial gravity and will help determine the existence of sex-based differences in response to spaceflight stressors. Moreover, I will determine sex-based differences during muscle recovery following disuse, and the long-term impact of circadian disturbance on muscle health and function. This study, which includes phenotypical and molecular outcomes, will assess the contribution of muscle clock genes and pathways to muscle health. Finally, targeted molecular assessment will help me use my diverse background (metabolism, neuromuscular, circadian) to explore other systems of interest that may be linked to muscle health and function (e.g., metabolic signaling pathways), and help characterize the key players that could be targeted with pharmacological approaches to provide new and effective countermeasures in future studies.