Research Paper Volume 12, Issue 9 pp 7963—7984
Metabolic switching is impaired by aging and facilitated by ketosis independent of glycogen
- 1 Department of Neuroscience, University of Florida, Gainesville, FL 32611, USA
- 2 University of Alabama at Birmingham, Birmingham, AL 35294, USA
- 3 Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA
- 4 Institute for Human and Machine Cognition, Ocala, FL 34471, USA
- 5 Institute on Aging, University of Florida, Gainesville, FL 32603, USA
Received: January 4, 2020 Accepted: March 31, 2020 Published: May 5, 2020
https://doi.org/10.18632/aging.103116How to Cite
Copyright © 2020 Hernandez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The ability to switch between glycolysis and ketosis promotes survival by enabling metabolism through fat oxidation during periods of fasting. Carbohydrate restriction or stress can also elicit metabolic switching. Keto-adapting from glycolysis is delayed in aged rats, but factors mediating this age-related impairment have not been identified. We measured metabolic switching between glycolysis and ketosis, as well as glycogen dynamics, in young and aged rats undergoing time-restricted feeding (TRF) with a standard diet or a low carbohydrate ketogenic diet (KD). TRF alone reversed markers of insulin-related metabolic deficits and accelerated metabolic switching in aged animals. A KD+TRF, however, provided additive benefits on these variables. Remarkably, the ability to keto-adapt was not related to glycogen levels and KD-fed rats showed an enhanced elevation in glucose following epinephrine administration. This study provides new insights into the mechanisms of keto-adaptation demonstrating the utility of dietary interventions to treat metabolic impairments across the lifespan.