“Effects of calorie restriction on markers of aging and longevity”, Luigi Fontana MD, PhD
Project Overview
Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. Recently, we have shown that long term CR results in profound and sustained beneficial effects on the major atherosclerosis risk factors and cardiac function in humans. All the above mentioned findings are consistent with long-term CR in monkeys and rodents. However, little is know about the effects of long-term CR in humans on markers of aging and longevity, including growth factors, hormones and inflammatory cytokines, which are involved in mediating some of the anti-aging effects observed in CR rodents.
Finding lean subjects who have successfully maintained long-term CR is extremely difficult. However, we have developed a unique research relationship with 26 highly motivated individuals, who have been practicing CR for an average of 6 years (range 3-15 years). Most of these individuals were already lean at the start of their CR program, and are dedicated to practicing severe CR with adequate protein and micronutrient intake in an effort to prevent age-associated chronic diseases and promote longevity. All of these individuals that we have tested are well educated and responsible individuals (business owners, physicians, college professors, lawyers and other professionals, etc.) who are extremely well read and informed in the areas of aging and CR. Moreover, they are very interested in participating in long-term research studies, and have already come to St. Louis from other cities in the US and Canada, at their own expense, for an initial evaluation at Washington University.
The major goal of this proposal is to determine potential markers of aging and longevity by providing comprehensive evaluation of the effects of long-term CR in humans. These markers include hormones, growth factors, and cytokines that affect insulin sensitivity, resting metabolic rate, body temperature, inflammation, cell proliferation, oxidative stress, that are involved in slowing the aging process. We will test the overall hypothesis that long-term CR in humans causes the same growth factor, hormonal, and metabolic changes that have been found in long-lived CR rodents. This hypothesis will be evaluated by studying a unique group of healthy subjects who have been practicing CR for an average of 6 years (range 3-15 years). These subjects eat high-quality diets that are high in protein and contain more than 100% of the RDA of all essential nutrients. Our goal is to determine whether CR results in the same adaptive responses of growth factors, hormones, and inflammatory cytokines in humans as those observed in CR rodents in which CR increases maximal longevity. These data will provide the foundation for future grant applications involving longitudinal follow-up measurements on these markers of aging and longevity.