Calorie Restriction, Longevity and Cognitive Function

besity is one of the most serious problems of public health and the fifth leading cause of death. It is estimated that 44% of diabetic load, 23% of heart ischemic load and 7-41% of all cancers load are related to obesity. Approximately 80% of older adults (+65years) have at least one of the above mentioned chronic diseases, and 50% have at least two chronic disease (1). Along with other organs, brain is also affected with aging and high calorie intake as Fitzpatrik and colleagues suggested in a review article that obese people have problems on decision-making, planning and solving skill, with fewer difficulties on the tasks of verbal fluency, learning and memory (2). In contrast, a reduction of calorie intake without malnutrition called “calorie restriction” (CR) has a wide range of benefits. Moderate CR can prevent or reverse the damaging effects of overweight/obesity, type 2 diabetes, hypertension, chronic inflammation and other age-associated metabolic diseases (1). As the first groups who worked on CR, Osborne et al. in 1917 showed that reducing calorie intake in rats increased their length of life. Since then, large amount of time and research efforts have been and continued to be devoted to the study of anti-aging and anti-cancer mechanisms underlying CR in yeasts, worms, insects, rodents and humans (3). Significant increase in life span has been reported when the nutrient availability drops between 30% and 75% of normal calorie provision, according to the species. Not only calorie restricted rodents lived longer than the adlibitum-fed counterparts but a significant part of them (about 30%) died without any apparent pathology, raising the striking possibility that aging is not necessarily tightly linked with costly pathologies (4). Preliminary results from human studies are reproducing many of the metabolic and physiological responses sobserved in rodents and monkeys. Short term CR (6-24 months) induces reduction of body weight, subcutaneous and visceral fat, lean body mass, insulin, energy expenditure, and core body temperature (5). Core body temperature, levels of dehydro-epiandrosterone sulfate (DHEAS) and insulin are biomarkers of CR and longevity in human similar to rodents and monkeys. In a 6-month CR related study on overweight individuals, a significant reduction of fasting insulin levels and core body temperature in CR and CR with exercise group has been reported; however, DHEAS and fasting glucose remained unchanged, as DHEAS falls 2-4% per year in humans. The other hypothesis to explain the antiaging effects of CR is reduced energy expenditure with a consequent reduction in the production of reactive oxygen species (ROS). In this study, a metabolic adaptation over 24 hours following 6 months of CR has also occurred (6). CR decreases serum insulin-like growth factor1 (IGF-1) concentration by approximately 40% in rodents. This is a key role in protection against cancer and slowing age; as IGF-1 promotes tumor development and inhibits apoptosis (3). Cognitive impairment and calorie restriction Evidence from clinical and basic researches points to a deep connection between brain function decline and metabolic dysregulation during senescence(definition). Excess nutrient availability may be detrimental to brain function. Conversely, a 30% reduction in O