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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44192-0 |
| _version_ | 1797388230747750400 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Alexander Popov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:37:47Z |
| format | Article |
| id | doaj.art-ceeb2da29c3a47b68b9403c949de291d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T22:37:47Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-ceeb2da29c3a47b68b9403c949de291d2023-12-17T12:23:26ZengNature PortfolioNature Communications2041-17232023-12-0114111210.1038/s41467-023-44192-0Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortexAlexander Popov0Nadezda Brazhe1Kseniia Morozova2Konstantin Yashin3Maxim Bychkov4Olga Nosova5Oksana Sutyagina6Alexey Brazhe7Evgenia Parshina8Li Li9Igor Medyanik10Dmitry E. Korzhevskii11Zakhar Shenkarev12Ekaterina Lyukmanova13Alexei Verkhratsky14Alexey Semyanov15College of Medicine, Jiaxing UniversityShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesFaculty of Biology, Moscow State UniversityDepartment of Neurosurgery, Privolzhskiy Research Medical UniversityShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesInstitute of Experimental MedicineShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesFaculty of Biology, Moscow State UniversityCollege of Medicine, Jiaxing UniversityDepartment of Neurosurgery, Privolzhskiy Research Medical UniversityInstitute of Experimental MedicineShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesFaculty of Biology, Medicine and Health, The University of ManchesterCollege of Medicine, Jiaxing UniversityAbstract 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.https://doi.org/10.1038/s41467-023-44192-0 |
| spellingShingle | 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 Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex Nature Communications |
| title | Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| title_full | Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| title_fullStr | Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| title_full_unstemmed | Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| title_short | Mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| title_sort | mitochondrial malfunction and atrophy of astrocytes in the aged human cerebral cortex |
| url | https://doi.org/10.1038/s41467-023-44192-0 |
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