When it comes to experience, I would say that Donaire would definitely dominate the ring, age might caught up to him, but, he would still find a way to show Santiago that he definitely deserved that title. But, if Donaire would be defeated, there is a higher chance that that would be his last battle, I think.
If Donaire would not retire after he is defeated, I think that it would have a hard time getting the title back as his.
Yes, that scenario is very much possible, but if this is going to be a close one, and Donaire losses it, then maybe we can a rematch. But if the fight is not even close and Donaire getting into the canvass and didn't win in the judges scorecard or getting knockout again, it's time for him to retire.
Because if he didn't then it might take some time for him to bounce (if there is no rematch), and by that time, he will be 40+ years old. And no way he can still fight as he might be just the stepping stone for this young fighters and we don't want to see that happen to Donaire.