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Tsesmelis, K.* ; Maity-Kumar, G. ; Croner, D.* ; Sprissler, J.* ; Tsesmelis, M.* ; Hein, T.* ; Baumann, B.* ; Wirth, T.*

Accelerated aging in mice with astrocytic redox imbalance as a consequence of SOD2 deletion.

Aging Cell 22:e13911 (2023)

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	Open Access Gold

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Aging of the central nervous system (CNS) leads to motoric and cognitive decline and increases the probability for neurodegenerative disease development. Astrocytes fulfill central homeostatic functions in the CNS including regulation of immune responses and metabolic support of neurons and oligodendrocytes. In this study, we investigated the effect of redox imbalance in astrocytes by using a conditional astrocyte-specific SOD2-deficient mouse model (SOD2^ako ) and analyzed these animals at different stages of their life. SOD2^ako mice did not exhibit any overt phenotype within the first postnatal weeks. However, already as young adults, they displayed progressive motoric impairments. Moreover, as these mice grew older, they exhibited signs of a progeroid phenotype and early death. Histological analysis in moribund SOD2^ako mice revealed the presence of age-related brain alterations, neuroinflammation, neuronal damage and myelin impairment in brain and spinal cord. Additionally, transcriptome analysis of primary astrocytes revealed that SOD2 deletion triggered a hypometabolic state and promoted polarization toward A1-neurotoxic status, possibly underlying the neuronal and myelin deficits. Conclusively, our study identifies maintenance of ROS homeostasis in astrocytes as a critical prerequisite for physiological CNS aging.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cns ; Sod2 ; Aging ; Astrocytes ; Brain ; Motoric Impairment ; Oxidative Stress ; Premature Aging; Manganese Superoxide-dismutase; Energy-metabolism; Mitochondrial; Lacking; Brain

ISSN (print) / ISBN 1474-9718

e-ISSN 1474-9726

Journal Aging Cell

Quellenangaben Volume: 22, Issue: 9, Article Number: e13911

Publisher Wiley

Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants Projekt DEAL
GRK 1789: Cellular and Molecular Mechanisms in Aging (CEMMA) - Deutsche Forschungsgemeinschaft (DFG)