Perhaps the simplest approach would be to simulate gravity for a period of time. A small single person centrifuge used by each astronaut for about an hour a day might counter-act most of the gravity related problems. Radiation just requires sheilding. At first just thick walls, but later a generated magnetic field could handle the charged particles, surfaces reflective to the most dangerous EM radiation could also be developed.
These issues will be surmounted, just like long distance ocean travel was overcome, so will space travel.