Beyond weight loss: current perspectives on the impact of calorie restriction on healthspan and lifespan.

Introduction: Changes to mental, physical, and physiological functions drive the complex processes underlying the variable progression of human aging. Nutritional interventions are one of the most promising non-pharmacological therapeutics to attenuate aging in humans. This narrative review aims to describe the implications of moderate and prolonged calorie restriction (CR) in healthy adults without obesity that occur beyond weight loss.Areas covered: Findings from CR studies, such as the CALERIE (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy) trials, the most rigorous trials to date examining a prolonged 25% CR, are described. The main areas covered include; changes to anthropometrics, energy metabolism, cardiometabolic health, inflammation and immune function, physical fitness, health behaviors, and mental health in response to weight loss (1-year) and weight loss maintenance (2-year).Expert opinion: CR presents a novel and effective therapeutic approach for improving healthspan and biomarkers of lifespan. To date, scientific evidence suggests that continued CR, under medical supervision, is accompanied with persistent and beneficial effects on health outcomes independent of weight loss. Mechanisms are yet to be fully elucidated, and novel dietary approaches that may similarly attenuate aging-related conditions should be explored and compared to traditional CR.