Loss of Brain Aerobic Glycolysis in Normal Human Aging
Open accessAbstract
The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG.
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Detrimental effects of impaired mitochondrial respiration in ApoE4 astrocytes could be magnified in later stages of life when the brain's metabolic dependency transitions from aerobic glycolysis to mitochondrial respiration.
“Thus, the detrimental effects of impaired mitochondrial respiration in ApoE4 astrocytes could be magnified in the later stages of life when the transition of metabolic dependency of the brain from aerobic glycolysis to mitochondrial respiration occurs.”
From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [24]
The Results and Discussion section (‘Whole brain AG decreases with age’; page unavailable) reports that aerobic glycolysis declines with age while whole-brain oxygen use remains relatively unchanged, supporting a shift in the relative contribution of these metabolic pathways. The paper studies cognitively normal human brains, not ApoE4 astrocytes, and does not test whether impaired mitochondrial respiration becomes more harmful later in life. It also does not establish a discrete transition to dependence on mitochondrial respiration. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the human brain, aerobic glycolysis is associated with the neuronal developmental stage and gradually decreases with age, whereas glucose usage for mitochondrial OXPHOS is relatively sustained.
“In the human brain, aerobic glycolysis is associated with the neuronal developmental stage, which gradually decreases with age, whereas glucose usage for mitochondrial OXPHOS is relatively sustained.24”
From ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes (2023) · cites this paper as [24]
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- Authors
- Goyal, M. S., Vlassenko, A. G., Blazey, T. M., Su, Y., Couture, L. E., Durbin, T. J., Bateman, R. J., Benzinger, T. L.-S., Morris, J. C., & Raichle, M. E.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Goyal, Manu S.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 26
- Issue
- 2
- Pages
- 353-360.e3
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5573225
- OpenAlex
- W2739598026
- Cited by
- 318
- References
- 16
- Citations by year
- 2026: 35 · 2025: 37 · 2024: 34 · 2023: 33 · 2022: 35 · 2021: 65 · 2020: 34 · 2019: 23 · 2018: 18 · 2017: 4
- FWCI
- 16.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Barnes-Jewish Hospital Foundation
- Charles F. and Joanne Knight
- James S. McDonnell Foundation
- McDonnell Center for Systems Neuroscience (22-3922-26239N)
- Radiological Society of North America
- NIH (NS06833, NS057901, NS048056, MH077967, P50AG005681, P01AG003991, P01AG26276, UF1AG032438, UL1TR000448, P30NS098577, R01EB009352)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain aging, aerobic glycolysis, brain glucose uptake, cerebral blood flow, brain metabolism, neoteny, cognitive aging, positron emission tomography
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Brain, Female, Glucose, Glycolysis, Humans, Male, Middle Aged, Positron-Emission Tomography
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