If that airliner was built with 1970's materials/technology AND it had to withstand temperatures of over 3000 degrees and airspeeds exceeding mach 20 every time it was used, yes, I would retire it way before 25 flights.
The airframe never gets over 200 degrees, and what the heck does the airspeed have to do with anything. Do you think the aluminum structure cares how fast it's moving?
The stress on a shuttle airframe is much less than on your typical airliner, since the shuttle is not pressurized. The airframe will basically last forever.
Better technology might be a reason to retire the shuttles, but so far, nobody has invented any.