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Age-Related Changes in Cerebral Oxidative Metabolism

Implications for Drug Therapy

  • Physiological Aspects of Aging
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Summary

Glucose metabolism in the brain is of central significance. It contributes to the synthesis of the neurotransmitters acetylcholine, glutamate, aspartate, γ-aminobutyric acid (GABA) and glycine, and yields adenosine triphosphate (ATP) as the driving force of almost all cellular and molecular work. Neuronal glucose metabolism is controlled antagonistically by insulin and cortisol via amplification and desensitisation of the insulin signal from the insulin receptor. Normal aging of mammalian brains is associated with numerous inherent metabolic changes. The metabolic changes that are of pivotal importance include probable primary inherent variations in the neuronal insulin receptor, the desensitisation of the neuronal insulin receptor by circulating cortisol and receptor dysfunction subsequent to changes in membrane structure and function.

As a consequence, slight aberrations in glucose/energy metabolism become obvious under resting conditions, indicating incipient variations of neuronal homeostasis as a common path in the aging process. Subsequent to the changes in glucose metabolism and energy production, variations occur in acetylcholine synthesis and release, extracellular concentration and receptor binding of glutamate and cytosolic Ca++ homeostasis. Additionally, free radical formation and membrane structure changes must be considered as primary changes during aging. Stressful events occurring more frequently during aging aggravate and prolong these changes that are accompanied by membrane lability.

There is increasing evidence that the sum of these metabolic variations develops in a self-propagating manner, following the principle of self-organised criticality. The progress from one metalabile steady state into another by additionally occurring events of small quantity may lead to increasing neuronal damage. As yet, there is no rational basis for any drug treatment to influence the process of normal cerebral aging. However, there is a reasonable basis for the assumption that long term mental activation contributes to the maintenance of mental capacity in old age.

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  1. Brain Metabolism Group, Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Im Neuenheimer Feld 220/221,69120, Heidelberg, Germany

    Siegfried Hoyer

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Hoyer, S. Age-Related Changes in Cerebral Oxidative Metabolism. Drugs & Aging 6, 210–218 (1995). https://doi.org/10.2165/00002512-199506030-00004

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