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 () and Alexey Semyanov ()
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Alexander Popov: Jiaxing University
Nadezda Brazhe: Russian Academy of Sciences
Kseniia Morozova: Moscow State University
Konstantin Yashin: Privolzhskiy Research Medical University
Maxim Bychkov: Russian Academy of Sciences
Olga Nosova: Institute of Experimental Medicine
Oksana Sutyagina: Russian Academy of Sciences
Alexey Brazhe: Russian Academy of Sciences
Evgenia Parshina: Moscow State University
Li Li: Jiaxing University
Igor Medyanik: Privolzhskiy Research Medical University
Dmitry E. Korzhevskii: Institute of Experimental Medicine
Zakhar Shenkarev: Russian Academy of Sciences
Ekaterina Lyukmanova: Russian Academy of Sciences
Alexei Verkhratsky: The University of Manchester
Alexey Semyanov: Jiaxing University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-44192-0

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