Heat and prolonged cooking have opposite effects on the two main solid components of meat: Both soften connective tissue, but at the same time they harden muscle fibers. Fortunately for the cook, the tenderizing of the connective tissue more than compensates for the hardening of the muscle fibers - that is, if the meat is cooked properly.
Granted, you can moist-cook meat slowly for several hours with a liquid at 140F without unduly toughening the muscle fibers. However, these time-temperature coordinates scarcely soften the connective tissue. To accomplish that mission with a 140F temperature, you need to cook the meat for at least six hours, a period that will likely toughen the muscle fibers and create a bacteria-engendered health risk.
At the other extreme, you can moist-cook meat at, say 212F. Within an hour or so at that comparatively high temperature, much of the collagen will have gelatinized. Unfortunately, much of the muscle fiber will have coagulated too much and toughened. And the meat will shrink appreciably.
Most of the time, two or three hours of slow moist cooking at 180F strikes a balance between softening the connective tissue and not hardening muscle fiber or risking contamination. The meat will properly done when the internal temperature reaches about 135F (measure with an instant thermometer). Further cooking will toughen and shrink the meat.
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