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

Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, …, Simpson SJ · 2014 · Cell Metabolism · Atlas ID SOL2014

What this study shows

Lifespan and cardiometabolic health were determined not by caloric intake but by the protein:carbohydrate ratio; a low protein ratio was associated with lower hepatic mTOR activation.

Abstract

ShowHide

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.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse, 25 ad libitum diets); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse, 25 ad libitum diets
Journal	Cell Metabolism
Year	2014
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cmet.2014.02.009 · PMID 24606899 · Free full text (PMC5087279)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

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
Dose	25 ad libitum diets differing in protein (5%–60%), fat (16%–75%), carbohydrate (16%–75%), and energy (8, 13, or 17 kJ/g of food) fed over a lifetime
Sample size	858 mice across 25 diets
Effect size	Median lifespan increased by approximately 30% (from 95 to 125 weeks) as the protein-to-carbohydrate ratio decreased; not influenced by total calorie intake
Limitations	not stated

In the Atlas

Links in the pathway map

Supports Fasting / caloric restriction inhibits mTORC1
Points the other way on Fasting / caloric restriction activates Longevity

Cite this paper

ShowHide

Solon-Biet, S. M., McMahon, A. C., Ballard, J. W., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., Gokarn, R., Khalil, M., Turner, N., Cooney, G. J., Sinclair, D. A., Raubenheimer, D., Le Couteur, D. G., & Simpson, S. J. (2014). The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metabolism. https://doi.org/10.1016/j.cmet.2014.02.009

@article{SOL2014,
  author       = {Solon-Biet, S. M. and McMahon, A. C. and Ballard, J. W. and Ruohonen, K. and Wu, L. E. and Cogger, V. C. and Warren, A. and Huang, X. and Pichaud, N. and Melvin, R. G. and Gokarn, R. and Khalil, M. and Turner, N. and Cooney, G. J. and Sinclair, D. A. and Raubenheimer, D. and Le Couteur, D. G. and Simpson, S. J.},
  title        = {{The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice}},
  journal      = {Cell Metabolism},
  year         = {2014},
  doi          = {10.1016/j.cmet.2014.02.009},
  note         = {PMID: 24606899},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SOL2014) [Data set]. https://mtor-atlas.org/study/SOL2014/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SOL2014,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SOL2014},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SOL2014/},
  doi          = {10.5281/zenodo.22059963}
}

Was this page useful?