I think the most important factor is the loss of gravity on the human body coupled with the loss of the Earths electromagnetic field. Our nervous systems have been effected by the Earths magnetic field since we were in utero and that's why people are effected by the phases of the Moon. The lack of gravity which has a huge electromagnetic component has a direct negative effect on our cells. The muscle spindles and mechanoreceptors must suffer the most which will than cause cerebellar cell atrophy and balance problems. I believe it doesn't matter how much the astronauts work out if they don't have some type of gravity their body's will deteriorate. But that's just what I believe. What do you believe?