The mechanism by which CR works to extend lifespan in multiple rodent species is of high relevance and significance to research into aging. Mitochondria do not seamlessly convert the mitochondrial membrane potential to chemical energy, i.e. ATP. Rather there are several possibilities for proton "leak" through the mitochondrial inner membrane that do not require passage through the ATPase and synthesis of ATP. The investigator formulates the hypothesis that it is really the rate and extent of these leak reactions that are both 1) major contributors to resting mitochondrial O2 consumption, and 2) major contributors to the production of reactive oxygen species (ROS). Caloric Restriction has been demonstrated consistently to increase lifespan, and to decrease several biochemical endpoints of mitochondrial and oxidative stress specifically in postmitotic tissues. The premise is that Caloric Restriction (CR), hypothyroidism, and modulation of dietary fat will decrease mitochondrial permeability (i.e. proton leak), therefore decreasing molecular Oxygen consumption, and presumably oxidative stress.