- Roberts, Megan N;
- Wallace, Marita A;
- Tomilov, Alexey A;
- Zhou, Zeyu;
- Marcotte, George R;
- Tran, Dianna;
- Perez, Gabriella;
- Gutierrez-Casado, Elena;
- Koike, Shinichiro;
- Knotts, Trina A;
- Imai, Denise M;
- Griffey, Stephen M;
- Kim, Kyoungmi;
- Hagopian, Kevork;
- McMackin, Marissa Z;
- Haj, Fawaz G;
- Baar, Keith;
- Cortopassi, Gino A;
- Ramsey, Jon J;
- Lopez-Dominguez, Jose Alberto
Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice.