So we know he defeated Madara, but we also know he didn't die of old age, because when he's brought back via edo tensei he's still youthful. Also Tobirama died during his prime, and as the Second Hokage, so Hashirama had to have died prior to this.
So Hashirama senju, possibly the most powerful shinobi to exist prior to the show, certainly the most powerful man alive, defeats the only other shinobi who could stand up to him, but he dies in his prime, how could this be?
Disease is a possibility but I feel with his legendary healing prowess, and being a reincarnation of Asura I feel like a disease isn't going to wipe him out. We know he didn't die as a result of his battle with Madara, because it was Madara's use of Kurama which led to Hashirama deciding the tailed beasts must be caged, and we see him having this discussion with kurama at some point. He also convenes a meeting of the five Kage, and seems perfectly well.
So Hashirama, the most powerful man alive, in the prime of his life, with the ability to control tailed beasts so they can't have been used as a weapon against him. What could possibly strike him down when he's stronger than ever?
So Hashirama senju, possibly the most powerful shinobi to exist prior to the show, certainly the most powerful man alive, defeats the only other shinobi who could stand up to him, but he dies in his prime, how could this be?
Disease is a possibility but I feel with his legendary healing prowess, and being a reincarnation of Asura I feel like a disease isn't going to wipe him out. We know he didn't die as a result of his battle with Madara, because it was Madara's use of Kurama which led to Hashirama deciding the tailed beasts must be caged, and we see him having this discussion with kurama at some point. He also convenes a meeting of the five Kage, and seems perfectly well.
So Hashirama, the most powerful man alive, in the prime of his life, with the ability to control tailed beasts so they can't have been used as a weapon against him. What could possibly strike him down when he's stronger than ever?