I have never completed the MR. However, I do up 1,000'/mi. pretty regularly and up 1,800' and 2,400'/mi. all winter long and frequently during the summer. The former is no problem but the latter makes my Achilles sit up and take notice. The shoulder strain is an issue during the winter but that has more to do with heavier pack weights. Everything depends on what you do regularly...1,000'/mi use to be daunting, now it's ho-hum.
I plan to do the MR this summer for the first time. If I go with a bunch of other MR noobs, the plan will be to return via the trail.