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Senescent Astrocytes Derived from Human Pluripotent Stem Cells Reveal Age-Related Changes and Implications for Neurodegeneration

Authors
Kim, DongyunYoo, Seo HyunYeon, Gyu-BumOh, Seung SooShin, Won-HoKang, Hoon- ChulLee, Cheol-KooKim, Hyung WookKim, Dae-Sung
Issue Date
Jun-2025
Publisher
International Society on Aging and Disease
Keywords
astrocytes; human pluripotent stem cells; cellular senescence; mitochondria; neurodegeneration; a cellular model of senescence
Citation
Aging and Disease
Indexed
SCIE
SCOPUS
Journal Title
Aging and Disease
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/67164
DOI
10.14336/AD.2024.0089
ISSN
2152-5250
Abstract
Astrocytes play a crucial role in maintaining brain homeostasis by regulating synaptic activity, providing metabolic support to neurons, and modulating immune responses in the central nervous system (CNS). During aging, astrocytes undergo senescence with various changes that affect their function and frequently lead to neurodegeneration. This study presents the first evidence of senescent astrocytes derived from human pluripotent stem cells (hPSCs). These senescent hPSC-derived astrocytes exhibited altered cellular and nuclear morphologies, along with increased expression of senescence-associated markers. Additionally, nuclear localization of NF kappa B, telomere shortening, and frequent signs of DNA damage were observed in these cells. Furthermore, senescent astrocytes showed defects in various critical functions necessary for maintaining a healthy CNS environment, including a reduced ability to support neuronal survival and clear neurotransmitters, synaptic debris, and toxic protein aggregates. Altered structural dynamics and reduced mitochondrial function were also observed in senescent astrocytes. Notably, treating hPSC-derived senescent astrocytes with chemicals targeting reactive oxygen species or an enzyme that regulates mitochondrial function can reverse senescence phenotypes. Thus, this study offers a valuable cellular model that can be utilized to investigate the mechanisms of brain aging and may present new avenues for discovering innovative therapeutic approaches for neurodegenerative diseases.
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Yu, Se Hyun
Anam Hospital (Department of Hepato-Biliary-Pancreatic Surgery, Anam Hospital)
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