Wear on the tires
Joe Mixon is a young man by almost every metric. Except the NFL's. He's 28 years old already and is heading into his 8th year in the NFL. Derrick Henry is entering year number nine, and he saw a drastic decline from years seven to eight. In year seven he went from 1,538 yards, and a 4.4 yards per carry average to 1,167 and a 4.2 yards per carry average. It's far more likely that Henry continues to slide down the line of production as he gets older. Henry was an elite-level runner at one point, averaging nearly or over five yards per carry for three straight years.
But age catches up to all of us. Mixon may be a young man by every metric of the word but he isn't so young that you should expect him to play at or near a Pro Bowl status. Running backs, typically, fade fast. Far faster than a quarterback does, mind you. Sometimes you can get to 30 and still be pretty good but eventually, the proverbial wheels fall off and you become a shell of yourself.
Mixon may be there, or at least, closing in on that part of his career. Daemon Pierce, Mixon's backup, will likely get more reps than many people expect.