Format

Send to

Choose Destination
EMBO J. 2017 Jun 1;36(11):1474-1492. doi: 10.15252/embj.201695810. Epub 2017 Apr 24.

Brain metabolism in health, aging, and neurodegeneration.

Author information

1
Laboratory of Neuroscience, National Institute on Aging, Baltimore, MD, USA camandolasi@mail.nih.gov mark.mattson@nih.gov.
2
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.

KEYWORDS:

aging; brain energetics; ketone bodies; metabolism

PMID:
28438892
PMCID:
PMC5452017
DOI:
10.15252/embj.201695810
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center