Health/age might play a part in it, but I think they'll call it quits when they finally have to admit that they cannot achieve that culture-transforming, "relevant" single and album that they're always chasing. It simply isn't possible in today's musical world.
When the new album is released and it is met with a collective whimper outside the U2 fan community, which of course it will be, my guess is they will gracefully bow out after the tour. UNLESS they can somehow abandon the dream of "relevance" and just make music for music's sake again. But I'm not optimistic, since they had a "beautiful, quiet, spiritual" album in Songs of Ascent, and they threw it away because it didn't have hit potential.