Caloric Restriction and Biomarkers of Aging

Calorie restriction (CR) is characterized by a reduction in calorie intake without malnutrition. In the context of geroscience, CR is a promising nutritional strategy that targets the biology of aging and therefore has the potential to delay the onset or slow the progression of age-related diseases. Life span extension by CR has been demonstrated in a variety of species, including yeast, drosophila, worms, rodents, and dogs, providing compelling evidence for the geroprotective potential of CR. In humans, optimizing health span is arguably a more meaningful goal of CR interventions and CR lifestyles. Numerous physiological effects of CR on biomarkers of human aging and health span have been explored, both in observational studies and in well-controlled intervention trials, providing an abundance of rich data that overwhelmingly support CR as a promising strategy for attenuating biological aging. The development of novel biomarkers of aging has advanced the field of geroscience and provided new opportunities for exploring the impact of CR on biological aging. In this chapter, we discuss the influence of CR on various biomarkers of aging and health span, with the biomarkers organized in three broad categories: cellular aging, phenotypic aging, and functional aging. We present results of CR studies in humans that demonstrate typical improvements in cardiometabolic indices, as well as effects on novel epigenetic biomarkers of cellular aging and the pace of biological aging that are based on DNA methylation. Finally, the chapter closes with highlights of ongoing CR initiatives funded by the National Institute on Aging and future directions for exploring numerous unanswered but important questions about the role of CR in enhancing health span.