Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain
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INVITED REVIEW
Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain Alexei Verkhratsky 1,2,3 Alexey Semyanov 6,8
&
Marcus Augusto-Oliveira 4 & Augustas Pivoriūnas 5 & Alexander Popov 6 & Alexey Brazhe 6,7 &
Received: 12 August 2020 / Revised: 5 September 2020 / Accepted: 9 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Astroglia represent a class of heterogeneous, in form and function, cells known as astrocytes, which provide for homoeostasis and defence of the central nervous system (CNS). Ageing is associated with morphological and functional remodelling of astrocytes with a prevalence of morphological atrophy and loss of function. In particular, ageing is associated with (i) decrease in astroglial synaptic coverage, (ii) deficits in glutamate and potassium clearance, (iii) reduced astroglial synthesis of synaptogenic factors such as cholesterol, (iv) decrease in aquaporin 4 channels in astroglial endfeet with subsequent decline in the glymphatic clearance, (v) decrease in astroglial metabolic support through the lactate shuttle, (vi) dwindling adult neurogenesis resulting from diminished proliferative capacity of radial stem astrocytes, (vii) decline in the astroglial-vascular coupling and deficient blood-brain barrier and (viii) decrease in astroglial ability to mount reactive astrogliosis. Decrease in reactive capabilities of astroglia are associated with rise of age-dependent neurodegenerative diseases. Astroglial morphology and function can be influenced and improved by lifestyle interventions such as intellectual engagement, social interactions, physical exercise, caloric restriction and healthy diet. These modifications of lifestyle are paramount for cognitive longevity. Keywords Ageing . Astrocyte . Astroglial perisynaptic cradle . Astroglial function . Synaptic transmission . Reactive astrogliosis . Neuroplasticity
The resilient ageing brain The age-dependent decrease in brain function is often portrayed as the main outcome of ageing which stems from an intrinsic propensity of the nervous tissue to degenerate; the view on progressive loss of neurones with age is a commonplace, while looming “pandemic” of dementia seems to erect
impenetrable barrier for keeping the quality of life of the ageing humanity. Nonetheless, when compared with other organs and systems, the brain ages most graciously; which has been documented already on one of the very first epidemiologic investigation of nearly 900 elderly (more than 80 years old), including 74 centenarians. This investigation, published in Cambridge in 1889, arrived to the following conclusions:
This article is part of the special issue on Aging Brain in Pflügers Archiv * Alexei Verkhratsky [email protected]
4
Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, Brazil
* Alexey Semyanov [email protected]
5
Department of Stem Cell Biology, State Research Institute Centre for Innov
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