“Effects of calorie restriction on markers of aging and longevity”, Luigi Fontana MD, PhD
Progress Report
We evaluated the long-term effect of calorie restriction (CR), defined as CR with optimal nutrition, on potential markers of aging and longevity in 28 middle-ages volunteers who had been on a CR diet for an average of 7 years (BMI 19.6±1.8 kg/m2, 8.7±7.3% body fat) and 28 age-matched healthy subjects consuming a typical Western diet (BMI 25.9±3.2 kg/m2, 24.6±6.5% body fat).
We found that long-term CR without malnutrition results in major improvements in indices of glucose tolerance and insulin action. Fasting glucose and insulin, the area under the curve (AUC) for insulin and the index of insulin sensitivity (ISI), calculated according to the method of Matsuda and Defronzo, were all significantly lower in the CR group than in the age and sex-matched Western diet group (Table 1). Accordingly, plasma adiponectin concentration was higher and plasma leptin, IL-6 and TNF-α/adiponectin ratio were lower in the CR group than in the Western diet group.
We also found that long-term CR in humans results in some of the same metabolic, hormonal and growth factors adaptations that are thought to be involved in mediating some of the anti-aging effects observed in CR rodents. In particular, we found that plasma IGF-1, PDGF-AB, TGF-β, total and free T3 concentration were lower, whereas plasma cortisol concentration was higher in the CR group than in the Western diet group (Table 2). The CR-mediated selective reduction in circulating triiodothyronine (T3) levels in rodents and monkeys, and now in humans are thought to play a key role in reducing metabolic rate and free radical production, whereas the reduction in chronic mitogenic and inflammatory stimuli is supposed to decelerate aging through down-regulation of p53 and NF-kB pathways. We didn’t find any difference in plasma IGFBP-3, THS, FT4 and DHEA-S concentration between the CR and the Western diet groups.
These data add relevant information to the growing research field of “healthy aging”, and the identification of metabolic and hormonal factors that can improve organ function, and consequently healthspan and lifespan in humans.