Reducing calorie intake for a comparatively short period of time very early in life is here shown to have life-long effects in mice. This provides more insight into the way in which metabolism in shorter-lived mammals has evolved to react to temporary famine conditions, producing more robust health and up to 40% longer life spans for life-long calorie restriction. It is interesting that even a short period of low calorie intake early in life can have the effects noted in this study.
We humans share the same evolutionary heritage of nutrient sensing mechanisms intended to alter our metabolic processes based on calorie intake, and the beneficial effects of calorie restriction on measures of health are quite similar to those in mice, but calorie restriction doesn't extend our life by anywhere near the same proportion. The consensus in the scientific community is that calorie restriction will extend human life by perhaps 5% or a little more. On the other hand, the health benefits are greater than those produced by any presently available medical technology or lifestyle choice.
The action of nutrients on early postnatal growth can influence mammalian aging and longevity. Recent work has demonstrated that limiting nutrient availability in the first three weeks of life (by increasing the number of pups, in the crowded litter (CL) model) leads to extension of mean and maximal lifespan in genetically normal mice. In this study we aimed to characterize the impact of early life nutrient intervention on glucose metabolism and energy homeostasis in CL mice. In our study we used mice from litters supplemented to 12 or 15 pups and compared those to control litters limited to 8 pups.
At weaning and then throughout adult life, CL mice are significantly leaner and consume more oxygen relative to control mice. At 6 months of age, CL mice had low fasting leptin concentrations, and low-dose leptin injections reduced body weight and food intake more in CL female mice than in controls. At 22 months, CL female mice also have smaller adipocytes compared to controls. Glucose and insulin tolerance tests show an increase in insulin sensitivity in 6 month old CL male mice, and females become more insulin sensitive later in life. Furthermore, β-cell mass was significantly reduced in the CL male mice and was associated with reduction in β-cell proliferation rate in these mice. Together, these data show that early life nutrient intervention has a significant lifelong effect on metabolic characteristics which may contribute to the increased lifespan of CL mice.