In every anime (very very very few exceptions) main characters and or highly skilled characters can be defeated under the right circumstances that fall within the parameters of anime.
For example in Rurouni Kenshin it would be outside the parameters of the anime if Kenshin was defeated because he was sucked into a black hole that appeared out of nowhere.
More specific to Naruto, during the battle of the Sonin, it was revealed that Tsunade can store chakra at a single spot behind her forehead. But the use of it shaves years of her projected life span (whatever it may be). If she were ever engaged in a battle where she found herself to have her body bruised, repeatedly, then chances are she would use her jutsu to recover her stored chakra so that at that particular moment she would be able to endure and kick some serious butt.
Also Tsunade is capable of aging. Generally in Naruto as you age you acquire more combat skills, but your body does age as well. As of right now Tsunade is at the latter end of her prime. I give her a few more years (12 years tops) as Hokage before she's the next best thing to Atom the Ant.