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

Ai Ling Lin, Wei Zhang, Xiaoli Gao, Lora Watts

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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 α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging.

Original languageEnglish
Pages (from-to)2296-2303
Number of pages8
JournalNeurobiology of Aging
Volume36
Issue number7
DOIs
StatePublished - Jul 1 2015

Bibliographical note

Funding Information:
The authors thank Drs. Brian Gold and Michael P. Murphy of the University of Kentucky and Dr. Arlan Richardson of University of Oklahoma Health Science Center for their valuable comments. The authors also thank Ms. Paula Thomason of the University of Kentucky for editing the article. Mass spectrometry analyses were conducted in the Metabolomics Core Facility of the Mass Spectrometry Laboratory at the University of Texas Health Science Center at San Antonio. This research was supported by NIH grant K01AG040164 and American Federation for Aging Research Grant # A12474 to Ai-Ling Lin.

Publisher Copyright:
© 2015 The Authors.

Keywords

  • Aging
  • Brain metabolism
  • Cerebral blood flow
  • Ketone bodies
  • Mammalian target of rapamycin
  • Neuroimaging
  • α-ketoglutarate

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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