Recent improvements in human longevity have highlighted the challenge of maintaining health throughout extended lifespans. This review examines how organisms regulate nutrient intake and metabolism, focusing on dietary protein's unique role in health and longevity. While caloric restriction enhances longevity, adherence to a low-calorie diet is challenging. Protein restriction represents an alternate nutritional intervention that improves longevity and health in model organisms and may be easier to translate to humans. However, its impacts are complex, and its mechanisms are poorly understood. The beneficial effects of protein restriction on metabolism and longevity may come at a cost to lean mass and physical resilience. Conversely, while public health recommendations often emphasize high protein intake, human epidemiological data and work on model organisms suggest that excessive protein consumption correlates with increased mortality. Understanding this paradox is crucial for developing evidence-based protein intake recommendations that balance longevity with physical performance.
Keywords: FGF21; LPHC; health span; high-carbohydrate diet; longevity; low-protein; protein restriction.