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On to your question. I have owned the ATH-M50s for a very long time back when they were first the flavor of the month and could be had for $100 and $90 (eBay).
The clamping force does adjust to your head over time, but I have not noticed any decrease in isolation.
My guess is your M50s are beginning to adjust to your head and you are linking that to losing isolation, but it is only making them more comfortable. I still have the original pads and they have not flattened out one bit. Mine still clamp pretty good but it is like they have adjusted so they mold to my head with just slight force compared to when I first got them.