The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice

Samantha M. Solon-Biet, Aisling C. McMahon, J. William O. Ballard, Kari Ruohonen, Lindsay E. Wu, Victoria C. Cogger, Alessandra Warren, Xin Huang, Nicolas Pichaud, Richard G. Melvin, Rahul Gokarn, Mamdouh Khalil, Nigel Turner, Gregory J. Cooney, David A. Sinclair, David Raubenheimer, David G. Le Couteur, Stephen J. Simpson

Research output: Contribution to journalArticlepeer-review

430 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)418-430
Number of pages13
JournalCell Metabolism
Volume19
Issue number3
DOIs
StatePublished - Mar 4 2014
Externally publishedYes

Fingerprint Dive into the research topics of 'The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice'. Together they form a unique fingerprint.

Cite this