ArticleAging and disease2024
Senescent Astrocytes Derived from Human Pluripotent Stem Cells Reveal Age-Related Changes and Implications for Neurodegeneration.
Article in Aging and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Astrocyte Senescence Disrupts the Extracellular Mitochondrial Compartment and Compromises Bioenergetic Support to Human Neurons.Antioxidants (Basel, Switzerland) · 2026Article
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Astrocyte States in Brain Aging and Neurodegeneration: At the Crossroads of Senescence and Reactivity.Neurochemical research · 2026Review
- Senescent Astrocytes: A New Player in Brain Aging and Cognitive Decline.Brain sciences · 2026Review
- From Neuron-Centric to Glia-Centric: How Aging Glial Networks Drive Neurodegenerative Disease.Journal of neurochemistry · 2026Review
- Immunosenescence and inflammaging in Parkinson's disease: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.Acta neuropathologica communications · 2025Article
- Doxorubicin Induces a Senescent Phenotype in Murine and Human Astrocytes.Journal of neurochemistry · 2025Article
- Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases.Stem cell research & therapy · 2025Review
- Internal Bisphenol Analogue Exposure in an Elderly Chinese Population: Knowledge from Dietary Exposure.Toxics · 2025Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
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 NFκB, 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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