It’s not an anime, per se, but the writing, voice acting and such are very much like an anime in the Like a Dragon series of games. Where it currently sits, all the characters are middle-aged or older. It also has a lot of existential dialogue and side stories that are extremely poignant, as someone who is also middle-aged in this time period.
The only actual anime I could even think of with main characters my age or older that I also enjoy is Cowboy Bebop; and that’s about 50-50 because of Faye and Edward. I’ve seen some episodes of Bartender but I wouldn’t go so far as to say I enjoy it yet. It’s a bit dry.
My favorite isekai is Farscape.
But if it has to be anime: Inuyasha.