The impact of low-protein high-carbohydrate diets on aging and lifespan

David G. Le Couteur, Samantha Solon-Biet, Victoria C. Cogger, Sarah J. Mitchell, Alistair Senior, Rafael de Cabo, David Raubenheimer, Stephen J. Simpson

Most research on nutritional effects on aging has focussed on the impact of manipulating single dietary factors such as total calorie intake or each of the macronutrients individually. More recent studies using a nutritional geometric approach called the Geometric Framework have facilitated an understanding of how aging is influenced across a landscape of diets that vary orthogonally in macronutrient and total energy content. Such studies have been performed using ad libitum feeding regimes, thus taking into account compensatory feeding responses that are inevitable in a non-constrained environment. Geometric Framework studies on insects and mice have revealed that diets low in protein and high in carbohydrates generate longest lifespans in ad libitum-fed animals while low total energy intake (caloric restriction by dietary dilution) has minimal effect. These conclusions are supported indirectly by observational studies in humans and a heterogeneous group of other types of interventional studies in insects and rodents. Due to compensatory feeding for protein dilution, low-protein, high-carbohydrate diets are often associated with increased food intake and body fat, a phenomenon called protein leverage. This could potentially be mitigated by supplementing these diets with interventions that influence body weight through physical activity and ambient temperature.