Can confirm. Built two bases with ~50 dupes, the game suffers when there's too much stuff to handle.
I think there's something to do with dupe pathfinding, since the pathfinding tree must be really huge by that point (since most of the map is revealed, with numerous accessible places). Same with order handling (how does the game decide if a given order must be done by that dupe and not another ?)
Perhaps there's something with complex gas and water pipe designs ? How does the game handle branches, does it scale well with big networks ?
Perhaps we can safely rule out the world simulation in general (temperatures, pression, gas movements...), especially if the calculations are done even if the tiles are not explored yet.
I see that the game only uses ~50% of my CPU when I get to that point, so it's not a bottleneck issue on the hardware side I guess.