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I would say that one of the biggest challenges is going to be maintaining a healthy body in a zero gravity environment. Not sure how long the longest stay at the Space Station has been, but does it even come close to 500 days?

Cosmonaut Valeri Polyakov holds the record for longest single spaceflight with a stay of 437 days on Mir.

http://en.wikipedia.org/wiki/Valeri_Polyakov

What's required to maintain a healthy body in zero gravity is still contradictory. One of the biggest problems is due to decreased immune system, which likely isn't caused by space itself but that 1/2 of all astronauts get less than 2 hours sleep in a 24 hour period while taking sleeping pills, which sleeping pills themselves are known to have detrimental effects on health in the long term. Apparently the other 1/2 don't get that much more than 2 hours, certainly nowhere near the 6 hour minimum for 'average' sleep.

IMO solving the sleep issue will solve a lot of the health problems. However, what's required for solving the sleep issue will likely also solve the remainder of the health problems, and I'd be willing to put money on it being simulating gravity for at least the persons sleep cycle.

I've wondered for a while if something as simple as a centrifuge-like hammock would work.

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