I do just as Xay said. Once they hit 45, I marry them off to whomever comes along next so they have a chance of having at least one child. Of course, there is always the chance that an orphan will show up on your doorstep and you can adopt them. But if that doesn't happen and you have no natural offspring, your game will end when the adults die.
That just happened to one of my families a few days ago and I started a new game in that game slot. When I went to do things like turning the TV off for the boob tube trophy or praising someone for preparing a meal for that one, I had to laugh---it seemed SO long since I got those trophies for my previous family, as it was in about its 6th or 7th generation when it ended. Talk about starting over from scratch, lol.