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.
Highlights
Patterns of energy consumption are a powerful regulator of mortality and longevity
Keto-adaptation is the coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low carbohydrate availability [38]. This process is enabled by metabolic switching from glycolysis to ketosis in which glucose oxidation is replaced by lipid oxidation and the synthesis of ketone bodies in the liver
These benefits in metabolic health were further bolstered by a high fat, low carbohydrate ketogenic diet (KD)
Summary
Patterns of energy consumption are a powerful regulator of mortality and longevity. In addition to caloric restriction, which has been extensively shown to extend maximum lifespan across species [1,2,3,4,5,6,7], time restricted feeding (TRF; referred to as meal feeding or intermittent fasting) may improve morbidity and mortality rates [8]. Long-term ketosis has been shown to prevent cognitive and physical declines associated with aging [11,12,13,14,15,16,17,18]. It remains to be determined, whether TRF alone can produce sufficient levels of ketosis to elicit similar health benefits and the extent to which TRF with a KD may have additive benefits on the healthspan of older adults and other animals
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