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

doi:10.1038/s41467-023-44192-0

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^*

^*Corresponding author for this work

Division of Neuroscience

Research output: Contribution to journal › Article › peer-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 language	English
Article number	8380
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-44192-0
Publication status	Published - 10 Dec 2023

Keywords

Humans
Aged
Astrocytes/metabolism
Cerebral Cortex/metabolism
Neurons/metabolism
Aging/metabolism
Glial Fibrillary Acidic Protein/metabolism
Atrophy/metabolism

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Popov, A., Brazhe, N., Morozova, K., Yashin, K., Bychkov, M., Nosova, O., Sutyagina, O., Brazhe, A., Parshina, E., Li, L., Medyanik, I., Korzhevskii, D. E., Shenkarev, Z., Lyukmanova, E., Verkhratsky, A., & Semyanov, A. (2023). Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex. Nature Communications, 14(1), Article 8380. https://doi.org/10.1038/s41467-023-44192-0

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title = "Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex",

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.",

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

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Popov, A, Brazhe, N, Morozova, K, Yashin, K, Bychkov, M, Nosova, O, Sutyagina, O, Brazhe, A, Parshina, E, Li, L, Medyanik, I, Korzhevskii, DE, Shenkarev, Z, Lyukmanova, E, Verkhratsky, A & Semyanov, A 2023, 'Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex', Nature Communications, vol. 14, no. 1, 8380. https://doi.org/10.1038/s41467-023-44192-0

TY - JOUR

T1 - Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex

AU - Popov, Alexander

AU - Brazhe, Nadezda

AU - Morozova, Kseniia

AU - Yashin, Konstantin

AU - Bychkov, Maxim

AU - Nosova, Olga

AU - Sutyagina, Oksana

AU - Brazhe, Alexey

AU - Parshina, Evgenia

AU - Li, Li

AU - Medyanik, Igor

AU - Korzhevskii, Dmitry E.

AU - Shenkarev, Zakhar

AU - Lyukmanova, Ekaterina

AU - Verkhratsky, Alexei

AU - Semyanov, Alexey

PY - 2023/12/10

Y1 - 2023/12/10

N2 - 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.

AB - 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.

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KW - Astrocytes/metabolism

KW - Cerebral Cortex/metabolism

KW - Neurons/metabolism

KW - Aging/metabolism

KW - Glial Fibrillary Acidic Protein/metabolism

KW - Atrophy/metabolism

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AN - SCOPUS:85179942925

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 8380

ER -

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

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Keywords

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