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Some men are just built to be big.  Take David Ortiz for example he is a big dude, and after having a down year two years ago at 33 (all the way down to a 101 OPS+, like our crop DH's have never been that bad in recent years ;) ), has roared back for 137 and 162 OPS+ years at 34 and 35.  And IMHO Prince is more innately talented that Big Papi.  
I am a big guy (I am ashamed to admit I am at least 70 lbs overweight), and like Prince I have ALWAYS been big.  Born at almost 11 pounds and never stopped growing.  Of course my wish and desire and effort is to try to lose weight, but it isn't as easy for some of us.  My point though is that I was born big and I have always been big and my body grew up and learned big.  I am able to do things as a big guy that all my skinny friends can do (lets play racquetball sometime, I will run you off the court :)), because my body knows no physical difference.  I would be willing to bet that if examined all of my joints and tendons and ligaments and thicker because they grew supporting more than a skinny guys did.  As far as physically breaking down I just turned 30, and I run several half marathons a year, play racquetball rigorously, coach soccer (well AYSO at least :) ), work out at least 4 times a week, and am still going strong.  I have had my fair share of injuries, aches and pains, but nothing that I wouldn't call within the realm of normal for any person as active as I am.  Certainly not as many as some one fragile like Rendon (ouch I know I know low blow, sorry about that).  And I am a nobody.  Not a big time athlete that has shown NO signs of wear like Prince.
It would definitely behoove Prince to lose weight not just for his joint health, but also heart health and generally feeling good about ones self.  And if contracted I hope the M's would encourage him to do that and provide him every opportunity to.  But I don't think it is a good reason to not sign him, or schedule him for an earlier baseball death.
As an aside I think it would be harder on a person who was skinny growing up, then ballooned late, rather than a guy like Prince who was always big, but I could be wrong, it is just an assumption, anyone have any facts on the matter?