Neuronal ageing from an intraneuronal perspective: Roles of endoplasmic reticulum and mitochondria

Emil C. Toescu, Alexei Verkhratsky

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The nature of brain ageing and the age-dependent decline in cognitive functions remains poorly understood. Physiological brain ageing is characterised by mild mental dysfunctions, whereas age-dependent neurodegeneration, as illustrated by Alzheimer disease (AD), results rapidly in severe dementia. These two states of the aged brain, the physiological and the pathological, are fundamentally different as the latter stems from significant neuronal loss, whereas the former develops without significant neuronal demise. In this paper, we review the changes in neuronal Ca2+ homeostasis that occur during brain ageing, and conclude that normal, physiological ageing is characterised mainly by a decrease of neuronal homeostatic reserve, defined as the capacity to respond effectively to functional and metabolic stressors, but does not reach the trigger required to induce neuronal death. In contrast, during neurodegenerative states, Ca2+ homeostasis is affected early during the pathological process and result in significant neuronal demise. We also review recent evidence suggesting that the endoplasmic reticulum (ER) might play an important role in controlling the balance between healthy and pathological neuronal ageing. © 2003 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)311-323
    Number of pages12
    JournalCell calcium
    Volume34
    Issue number4-5
    DOIs
    Publication statusPublished - Oct 2003

    Keywords

    • Endoplasmic reticulum
    • Mitochondria
    • Neuronal ageing

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