Lifespan and cardiometabolic health were determined not by caloric intake but by the protein:carbohydrate ratio; low protein ratio suppressed hepatic mTOR.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse, 25 ad libitum diets |
| Journal | Cell Metabolism |
| Year | 2014 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.cmet.2014.02.009 · PMID 24606899 · Free full text (PMC5087279) |
The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation.
| Intervention | Dietary – 25 diets varying protein:carb:fat, ad libitum |
| Target | Nutrient/mTOR signaling (dietary protein) |
| Model | Mouse (25 ad libitum diets) |
| Effect | Macronutrient ratio (low protein, high carb), not calorie intake, optimizes cardiometabolic health and longevity |