It seems like in most of the series tagged with 'age gap' the characters are only a few years apart, but I'm looking for recommendations for manga where there is a noticeable difference in the two characters ages (like 20+ years).

Thanks! 😀

Koi ga Ochitara is a good one. It's more on the mature side, though, so it may not be what you're looking for if you want a childish or high school younger character.

Tonari ni if you can get past the unconventional art (I personally love it). Same as above, more mature characters. Not yaoi. The younger character's thought process when he encounters the other character is captivating.

Any "seme raised the uke" or vice versa kind of manga. Yuuutsu na Asa is a good one if you're fine with historical. Complex characters and great character growth. It's a slow burn, though.