Aging
Navigate
Submit an Article
Research Paper|Volume 12, Issue 9|pp 7963—7984

Metabolic switching is impaired by aging and facilitated by ketosis independent of glycogen

Abbi Hernandez1,2, Leah Truckenbrod1, Quinten Federico1, Keila Campos1, Brianna Moon1, Nedi Ferekides1, Meagan Hoppe1, Dominic D’Agostino3,4, Sara Burke1,5
  • 1Department of Neuroscience, University of Florida, Gainesville, FL 32611, USA
  • 2University of Alabama at Birmingham, Birmingham, AL 35294, USA
  • 3Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33612, USA
  • 4Institute for Human and Machine Cognition, Ocala, FL 34471, USA
  • 5Institute on Aging, University of Florida, Gainesville, FL 32603, USA
Received: January 4, 2020Accepted: March 31, 2020Published: May 5, 2020
https://doi.org/10.18632/aging.103116

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.