Take that running back who carries the ball 30 times every game vs the running back who carries the ball 20 times every game, into week 15 and there will on average be a distinct difference, talent levels aside. Now extend that 3 years into their careers. Again, you're looking for absolutes, they don't exist. Fatigue is real, it is related to performance and it is related to injury. How much and to what extent that effects each individual is different and part of what teams are paying more attention to. Which also only includes the physical, the mental side is an entirely different topic. I'm sure it's not relevant though......