I have always had this issue when the game has run for a long time, getting worse and worse as the game goes on, until it is unplayable. Autosave says there wasn't enough memory to save the game, the game exits to main menu, then you can't load a game because there's not enough memory to load a game, and the autosave file is corrupted. A quick search will tell you this is a common problem. I've encountered it on 64 bit Win7, and 64 bit Win10, both with large amounts of memory and high end graphics cards. My current system is Win10, 64 bit, 64GB memory, Nvidia Quadro P5000 with 16GB memory, game purchased through Steam.
I tend to play with a lot of stars. My current game, which is having this issue fairly early on, is 1400 stars, 15 x 15 sectors, elliptical, 10 autogenerated empires, lots of weak pirates.