Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.
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.
Lin AL1, Zhang W2, Gao X3, Watts L4.
1Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: firstname.lastname@example.org.
2Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
3Institutional Mass Spectrometry Laboratory, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
4Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Neurobiol Aging. 2015 Mar 25. pii: S0197-4580(15)00182-7. doi: 10.1016/j.neurobiolaging.2015.03.012. [Epub ahead of print]
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Julie A. Mattison,1,* George S. Roth,2 T. Mark Beasley,3 Edward M. Tilmont,1 April H. Handy,1,4 Richard L. Herbert,5Dan L. Longo,1 David B. Allison,6 Jennifer E. Young,1 Mark Bryant,7 Dennis Barnard,7 Walter F. Ward,8 Wenbo Qi,9Donald K. Ingram,10 and Rafael de Cabo1,#
1Laboratory of Experimental Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA
2GeroScience, Pylesville, MD 21132, USA
3Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
4SoBran, Inc., Burtonsville, MD 20866, USA
5National Institute of Allergy and Infectious Disease, NIH, Dickerson, MD 20842, USA
6Office of Energetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
7Division of Veterinary Resources, NIH, Bethesda MD 20892, USA
8Department of Physiology, University of Texas Health Science Center at San Antonio, TX 78229, USA
9Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, TX 78229, USA
10Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA
PMCID: PMC3832985 NIHMSID: NIHMS528393
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John O. Holloszy1 and Luigi Fontana1,2
1 Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri, USA
2 the Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanitá, Rome, Italy
Please address correspondence to: John O. Holloszy, MD, Professor of Medicine, Division of Geriatrics and Nutritional Sciences, Washington University School of Medicine
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