This study is designed to investigate the effectiveness of a new exercise device, multi-mode exercise device or M-MED, for use during long-duration space flights for the maintenance of cardiovascular and musculoskeletal fitness of astronauts. The M-MED is gravity independent and provides both the high force resistance and low force rowing type resistance. To date the results indicate that foot forces in resistance mode exercise on M-MED are similar to those seen using free weight exercises. Electromyography (EMG) studies demonstrate that similar activation levels are seem in key muscles during either M-MED based or free weight resistance exercise. EMG during rowing demonstrate that the thigh, leg, and arm muscles are robustly activated. Endurance mode exercise was also found to stimulate recruitment of the muscles which support the spine. In a recently completed study, 32 subjects (16 male, 16 female) completed 5 weeks of combined resistance and endurance training using the M-MED. Muscle strength increased ~20% while aerobic fitness measured as maximal oxygen consumption (VO2max) increased ~8%. M-MED training increased time to hand grip fatigue by ~70% and leg extension fatigue by ~27%. Thigh muscle cross sectional area increased ~11% as a result of training. Additional deliverables include cross validation of VO2max testing results between the M-MED device and laboratory standard cycle ergometry based testing protocols. As requested by NASA, additional studies have demonstrated that M-MED based exercise can increase the size and strength of the calf and hamstrings muscle groups. These results demonstrate that the M-MED device can be used for both training and physical work capacity testing providing a platform for in-flight assessment. In summary, findings to date indicate that the gravity independent M-MED is a viable option for resistance- and endurance-mode exercise during flight and/or planetary exploration thereby addressing two critical risks: 1) Cardiovascular deconditioning; 2) Decreased muscle strength, endurance, and size (atrophy). Endurance mode exercise may have the added benefit of maintaining and, possibly, improving endurance of arm muscles of flight crews as well as aiding in the maintenance of lower back stability and loading during flight and planetary exploration. Presentations at workshops and meetings are listed below and also in the Bibliography section: Countermeasure Exercise Using a Single, Gravity Independent, Device to Prevent Cardiovascular and Muscular Deconditioning. J. Cotter, T. Owerkowicz, F. Haddad, P. Tesch, V. Caiozzo, G. Adams. American Society for Gravitational and Space Biology Annual Meeting, 2011. Resistance and aerobic flywheel training improves muscle strength and aerobic capacity in ambulatory subjects. Owerkowicz T, Cotter JA, Yu AM, Camilon ML, Hoang T, Baker MJ, Pandorf C, Kreitenberg A, Baldwin KM, Tesch PA, Caiozzo VJ, Adams GR. 18th Humans in Space symposium of the International Academy of Astronauts. Houston, TX, 2011. Gravity-independent flywheel exercise training improves aerobic capacity and muscle strength in ambulatory subjects. Owerkowicz T, Cotter JA, Tesch PA, Caiozzo VJ, Adams GR. Experimental Biology Washington, DC, 2011 DNA Methylation is Altered in Human Skeletal Muscle in Response to Exercise Training. Shlomit Radom-Aizik, Fadia Haddad, Tomasz Owerkowicz, Joseph M. Devaney, Eric P. Hoffman, Per A. Tesch, Gregory R. Adams. American College of Sports Medicine Annual Meeting, 2012 Influence of 10 days of unilateral lower limb suspension and combined exercise training on human vastus lateralis and soleus muscles. J. Cotter, F. Hadad, A. Yu, T. Hoang, M. Baker, P. Tesch, K. Baldwin, V. Caiozzo, G. Adams. Experimental Biology Annual Meeting, 2012. The presence and regulation of antisense long non-coding RNA with altered myosin expression in exercising human muscle. Clay E. Pandorf, Fadia Haddad, Tomasz Owerkowicz, Kenneth M. Baldwin, Vincent J. Caiozzo, Gregory R. Adams. Experimental Biology, 2012. The Effects Of Muscle Unloading With And Without Exercise Countermeasures On Loading Sensitive Cellular And Molecular Biomarkers. G. Adams, J. Cotter, C. Pandorf, F. Haddad, P. Tesch, K. Baldwin,V. Caiozzo. NASA Human Research Program (HRP) Meeting, 2012. Counteracting decrements in muscle function and aerobic capacity during unloading utilizing a gravity independent device. Cotter J, Hoang T, Yu A, Tesch P, Caiozzo V, Adams G. Podium presentation at the Annual Meeting for the American College of Sports Medicine, San Francisco, CA, 2012.