A survey of calorie restriction in many mouse breeds finds that it doesn't work to extend healthy life in all, and that difference appears to be related to the degree to which calorie restriction results in fat loss. This presents an interesting complication, given that it has been clearly demonstrated that surgically removing visceral fat extends life in mice, and the human studies of calorie restriction show unambiguously positive results on health: "Since the 1930s scientists have proposed food restriction as a way to extend life in mice. Though feeding a reduced-calorie diet has indeed lengthened the life spans of mice, rats and many other species, new studies with dozens of different mouse strains indicate that food restriction does not work in all cases. ... [Researchers] studied the effect of food restriction on fat and weight loss in 41 genetically different strains of mice. The scientists then correlated the amount of fat reduction to life span. The answer: Mice that maintained their fat actually lived longer. Those that lost fat died earlier. ... Indeed, the greater the fat loss, the greater the likelihood the mice would have a negative response to dietary restriction, i.e., shortened life. This is contrary to the widely held view that loss of fat is important for the life-extending effect of dietary restriction. It turns the tables a bit."
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