Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex

Alexander Popov, Nadezda Brazhe, Kseniia Morozova, Konstantin Yashin, Maxim Bychkov, Olga Nosova, Oksana Sutyagina, Alexey Brazhe, Evgenia Parshina, Li Li, Igor Medyanik, Dmitry E. Korzhevskii, Zakhar Shenkarev, Ekaterina Lyukmanova, Alexei Verkhratsky, Alexey Semyanov

Research output: Contribution to journalArticlepeer-review

Abstract

How aging affects cells of the human brain active milieu remains largely unknown. Here, we analyze astrocytes and neurons in the neocortical tissue of younger (22–50 years) and older (51–72 years) adults. Aging decreases the amount of reduced mitochondrial cytochromes in astrocytes but not neurons. The protein-to-lipid ratio decreases in astrocytes and increases in neurons. Aged astrocytes show morphological atrophy quantified by the decreased length of branches, decreased volume fraction of leaflets, and shrinkage of the anatomical domain. Atrophy correlates with the loss of gap junction coupling between astrocytes and increased input resistance. Aging is 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 is observed. Thus, brain aging is associated with the impaired morphological presence and mitochondrial malfunction of cortical astrocytes, but not neurons.

Original languageEnglish
Article number8380
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 10 Dec 2023

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