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

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

doi:10.1016/j.neurobiolaging.2015.03.012

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

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

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

66 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 language	English
Pages (from-to)	2296-2303
Number of pages	8
Journal	Neurobiology of Aging
Volume	36
Issue number	7
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.03.012
State	Published - Jul 1 2015

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

Funding

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.

Funders	Funder number
Hartford Foundation/American Federation	A12474
National Institutes of Health (NIH)	K01AG040164
National Institutes of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)	KL2TR001118
National Center for Advancing Translational Sciences (NCATS)

Keywords

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

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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Cite this

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title = "Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain",

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.",

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N2 - 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.

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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