Aging impairs astrocytes in the human cerebral cortex

Alexander Popov; Nadezda A. Brazhe; Kseniia I. Morozova; Яшин Константин Сергеевич; Maxim L. Bychkov; Olga Nosova; Oksana I. Sutyagina; Alexey Brazhe; E. Yu. Parshina; Li Li; Igor Aleksandrovich Medyanik; Dmitriy E. Korzhevsky; Zakhar O. Shenkarev; Ekaterina N. Lyukmanova; Alexei Verkhratsky; Alexey V. Semyanov

doi:10.1101/2022.10.31.514523

NeurosciencebioRxivOct 31, 2022

Preprint

Aging impairs astrocytes in the human cerebral cortex

Alexander Popov iD, Nadezda A. Brazhe iD, Kseniia I. Morozova, Яшин Константин Сергеевич iD, Maxim L. Bychkov iD, Olga Nosova iD, Oksana I. Sutyagina iD, Alexey Brazhe iD, E. Yu. Parshina iD, Li Li iD, Igor Aleksandrovich Medyanik iD, Dmitriy E. Korzhevsky iD, Zakhar O. Shenkarev iD, Ekaterina N. Lyukmanova iD, Alexei Verkhratsky iD, Alexey V. Semyanov iD

Abstract

How aging affects cellular components of the human brain active milieu remains largely unknown. We analyzed astrocytes and neurons in the neocortical access tissue of younger (22 - 50 years) and older (51 - 72 years) adult patients who underwent glioma resection. Aging decreased the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The total amount of protein was decreased in astrocytes and increased in neurons. Aged astrocytes showed morphological dystrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shrinkage of the anatomical domain. Dystrophy correlated with the loss of gap junction coupling between astrocytes and increased input resistance. Aging was accompanied by the upregulation of glial fibrillary acidic protein (GFAP) and downregulation of membrane-cytoskeleton linker Ezrin associated with leaflets. No significant changes in neuronal excitability or spontaneous inhibitory postsynaptic signaling were observed. Thus, brain aging is associated with the impaired morphological presence and mitochondrial malfunction of astrocytes, but not neurons.

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