Finally a person on the same idea as me i have looked at the problems with a long yoage in space without the ability to refuel and have a few problems but solutions to all but the matter of fuel.
1 air simpley prosses the air elements are never destroyed so the oxygen you need will always be thare.
2 0 gravity will mean the bones will never have foces on them so will become weak, but a machine that puts the bone under a acceptable amount of force for a given time the bones sould not deteriate. or if the 'ship' was spinning constantly you inside would feel a force that mimics gravity but in reverse so you fal away from the center in a similar way to a waight on a string when you spin it.
3 food, a hecter of land can support 10 people though out the year but can only support 1 cow. enough space to grow plants will mean enough food. the oxygen situation will also be helpped by the plants as 25m squared of leaf space supports one man.
4 the time it takes, a huge crew would be needed to provide a huge geane pool to stop mutations as any gerney to another planet would take a very long time other many generations unless criogenit freezing could occor wile the jouny there is automated.
5 fuel, ahe. We would need a rocket engine or an engine that works with pressure being the only way to move through space, although only a 2 large bursts of energy would be recurered as space has no friction. a nucler engine could not be used because a reator generates electrisity wich could not be used for propoltion. a nucluar engine could be used to power the ship but not for propoltion, so the nuclar power was my thought on the ship as well. We are still left with the propoltion problem.

ps. sorry for my bad spelling.