Seconding The Push Man and other stories, Adolf and Pluto.

Also, Paradise Town and Ressentiment are others I think you might enjoy.

http://kittenpatriot.wordpress.com/

Uh actually, whoever suggested Berserk is wrong, but not in the wrong as you should read Berserk anyway, 'cos it's bloody awesome. No pun intended.
Because in fact, Guts is only in his mid-twenties currently (Millennium Falcon Arc) in the manga. Estimates range from as low as 22 years of age up to 26 years of age. It only seems like a long time because of all the shit he's been through, and the manga's been going for like 20 years now.

As for 40+ year old protagonists... Brook from One Piece.
😉

If you were to go there and come back to me hurt, I will take your place.. and pull everything you hate.. into destruction...
I will erase anything that hurts you.. from the face of this world.

Most awesome (I can't honestly call it "best", though) old man manga of all time is, naturally, Oyaji. A better but not quite as awesome one is Ore wa Mada Honki Dashitenai Dake.
Unfortunately, neither has been translated yet. But one never knows, stranger things have happened.

Hmm, Natsunokumo has several main characters (females included) that are probably over 40, but it's hard to say for sure. I don't think we're ever told their actual ages.