4.5 Article

Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain

Journal

NEUROBIOLOGY OF AGING
Volume 36, Issue 7, Pages 2296-2303

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.03.012

Keywords

Aging; Brain metabolism; Cerebral blood flow; Neuroimaging; Ketone bodies; alpha-ketoglutarate; Mammalian target of rapamycin

Funding

  1. NIH [K01AG040164]
  2. American Federation for Aging Research Grant [A12474]

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Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and alpha-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and a-ketoglutarate may play important roles in preserving brain physiology in aging. (C) 2015 The Authors. Published by Elsevier Inc.

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