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Title: Three cellular mechanisms contributing to aging of the brain

Joe Herbert

University of Cambridge, UK

Biography

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Abstract

It is proposed that there are three major cellular pathways than contribute to brain aging.  Activities of each overlap and are cross-linked. Age-related systemic changes moderate these mechanisms to variable extents. (1) Reduced growth factor activity, particularly BDNF and TrkB, are associated with neuronal and synaptic dysfunction and loss of plasticity. Age-related increases in cortisol, and decreases in DHEA, encourage changes in BDNF. (2) Microglia become activated with age, and release cytokines such as IL6 and TNFa, which damage neurons and predispose them to damage by other agents.  Peripheral low-level inflammation, a feature of increasing age, promotes inflammatory responses in microglia.  Corticoids are also pro-inflammatory in the brain. (3) Astrocytic function (eg aquaporin-4) is also impaired with age, and this has adverse effects both on the blood-brain barrier and on synaptic function, plasticity and integrity. The relative contribution of each factor to overall ageing will vary individually, and be reflected in the degree and nature of cognitive decline and emotional dysfunction.