In July of Konoha's forty-ninth year, four months after the end of the Third Shinobi World War, Uzumaki Mizusu—the first Nine-Tails Jinchuriki of Konoha and the wife of the God of Shinobi—passed away.
With her death, the last elder who had lived before Konoha's founding was officially gone. The earliest history had truly become history. At the same time, it marked the complete decline of the Senju Clan. Only Tsunade, a direct descendant suffering from hemophobia, remained, while the branch families were few in number and mostly assimilated into Konoha.
Because Mizusu had been the Nine-Tails Jinchuriki, Konoha's higher-ups did not hold a grand funeral. Instead, only a small circle of senior officials paid their respects before she was buried in Senju Hashirama's grave, the two interred together.
With Mizusu's death, the matter of the Nine-Tails Jinchuriki became a thorny issue. However, before Uzumaki Mizusu passed, the Nine-Tails' seal had already been transferred to Kushina Uzumaki. After all, they could not wait until she truly died to make the transfer; that would have resulted in the Nine-Tails' rampage.
Therefore, rather than saying Mizusu died of illness, it would be more accurate to say that she died because the Nine-Tails was extracted from her. Of course, even if the Nine-Tails had not been removed, she would not have lasted much longer. The transfer had been her own suggestion as well.
The funeral lasted a week, after which everything gradually returned to calm.
Mizusu's death did not cause too much trouble for Konoha as it now stood.
In August of the same year, after the dust had settled, Konoha's princess, one of the legendary Sannin, and once the strongest medical ninja, Lady Tsunade, left Konoha.
The outcome came as a surprise to many, yet it was also understandable. Tsunade's hemophobia was common