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Cited by 90Genetics, Aging, and Longevity in Model OrganismsDietary Effects on HealthDiet and metabolism studies

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

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Lin, Ai-Ling, Zhang, Wei, Gao, Xiaoli, Watts, Lora·2015·Neurobiology of Aging
DOI 10.1016/j.neurobiolaging.2015.03.012PMC PMC4457572
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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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  • Ketone bodies readily cross the blood brain barrier and can act as a potent fuel for the brain.

    “These ketone bodies readily cross the blood brain barrier and can act as a potent fuel for the brain35–37.”

    From APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice (2020) · cites this paper as [37]

    The Discussion states that ketone bodies are an alternative fuel for brain cells and can support most, if not all, basal neuronal oxidative metabolism. It does not state that they readily cross the blood–brain barrier; it says brain ketones in the studied rats appeared to come primarily from astrocytes rather than blood. (LLM, conf=0.86)

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Cited by

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Authors
Lin, A.-L., Zhang, W., Gao, X., & Watts, L.
Affiliations
  • University of Kentucky (US)
  • The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Lin, Ai-Ling
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2015-07
Volume
36
Issue
7
Pages
2296-2303
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/j.neurobiolaging.2015.03.012
PMC
PMC4457572
OpenAlex
W2054110063
Cited by
90
References
7
Citations by year
2026: 7 · 2025: 7 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 4 · 2020: 10 · 2019: 13 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 3
FWCI
2.56
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
Funders
  • NIH (K01AG040164)
  • American Federation for Aging Research (A12474)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
Keywords
caloric restriction, ketone bodies, brain aging, cerebral blood flow, brain glucose uptake, lactate, alpha-ketoglutarate, citrate, TCA cycle, mitochondrial metabolism, neuroprotection
MeSH terms
Aging, Animals, Brain, Cerebrovascular Circulation, Ketone Bodies, Male, Rats, Inbred F344, Caloric Restriction

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