(P26-007-25) Leveraging Phytoestrogens to Preserve Muscle Function on the Lunar Surface

Objectives: After years of exploring low Earth orbit, NASA plans to send the next man and first woman to the Moon. However, exposure to lunar gravity has significant physiological effects characterized by loss of muscle mass, weakness and decreased bone density. Resveratrol (RSV), a naturally occurring polyphenol has been identified as a potent nutritional countermeasure; however, its pleiotropic effect hinders the ability to identify the primary cellular pathways through which it delivers its benefits. Furthermore, its efficacy in simulated lunar gravity is unknown. Based on the benefits observed with RSV supplementation during unloading, and the striking differences observed between males and females, we hypothesize that Estrogen-Receptor (ER) α may be necessary to preserve muscle health and function in a lunar gravity analog.

Methods: Forty adult male Wistar rats (10/group) were followed for 14 days. A control group was kept freely ambulating, and three groups were exposed to simulated lunar gravity (0.2g) using the rat partial weight-bearing (PWB) model. Two groups received daily RSV supplementation (200 mg/kg), and one group also received an ER antagonist (MPP, 25µg). Muscle function was longitudinally assessed using voluntary grip strength, nerve-stimulated force production, fatigue resistance protocols, and electrical impedance myography.

Results: Animals exposed to PWB20 experienced muscle deconditioning characterized by a 6.4 % and 22.1% drop in body weight and soleus mass, respectively, and a 17.5% reduction in grip strength within 7 days of unloading. Animals supplemented with RSV had grip strength values comparable to the controls. Rats that received RSV supplementation and MPP displayed a 24.5% reduction in grip strength within 7 days.

Conclusions: These preliminary results suggest that phytoestrogens such as RSV can preserve muscle function during disuse and that ERa may be critical to their action in skeletal muscles. The outcomes of this study will offer insights into the role of ER and could lead to the development of targeted therapies for disuse atrophy following bed rest, injury, and metabolic diseases such as type 2 diabetes and sarcopenia.

Funding Sources: The Rhode Island Foundation