Mechanisms of astrocyte aging in reactivity and disease

Abstract Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor how they contribute to neuronal dysfunction and disease risk as organisms age. Here, we examine the transcriptional, cell biology, and functional differences in a...

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Main Authors: Holly K. Gildea, Shane A. Liddelow
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Molecular Neurodegeneration
Subjects:
Online Access:https://doi.org/10.1186/s13024-025-00810-7
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author Holly K. Gildea
Shane A. Liddelow
author_facet Holly K. Gildea
Shane A. Liddelow
author_sort Holly K. Gildea
collection DOAJ
description Abstract Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor how they contribute to neuronal dysfunction and disease risk as organisms age. Here, we examine the transcriptional, cell biology, and functional differences in astrocytes across normal aging. Astrocytes at baseline are heterogenous, responsive to their environments, and critical regulators of brain microenvironments and neuronal function. With increasing age, astrocytes adopt different immune-related and senescence-associated states, which relate to organelle dysfunction and loss of homeostasis maintenance, both cell autonomously and non-cell autonomously. These perturbed states are increasingly associated with age-related dysfunction and the onset of neurodegeneration, suggesting that astrocyte aging is a compelling target for future manipulation in the prevention of disease.
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spelling doaj-art-d2c78e9990784ef0bc31e795a83deda72025-08-20T02:15:07ZengBMCMolecular Neurodegeneration1750-13262025-02-0120111410.1186/s13024-025-00810-7Mechanisms of astrocyte aging in reactivity and diseaseHolly K. Gildea0Shane A. Liddelow1Institute for Translational Neuroscience, NYU Grossman School of MedicineInstitute for Translational Neuroscience, NYU Grossman School of MedicineAbstract Normal aging alters brain functions and phenotypes. However, it is not well understood how astrocytes are impacted by aging, nor how they contribute to neuronal dysfunction and disease risk as organisms age. Here, we examine the transcriptional, cell biology, and functional differences in astrocytes across normal aging. Astrocytes at baseline are heterogenous, responsive to their environments, and critical regulators of brain microenvironments and neuronal function. With increasing age, astrocytes adopt different immune-related and senescence-associated states, which relate to organelle dysfunction and loss of homeostasis maintenance, both cell autonomously and non-cell autonomously. These perturbed states are increasingly associated with age-related dysfunction and the onset of neurodegeneration, suggesting that astrocyte aging is a compelling target for future manipulation in the prevention of disease.https://doi.org/10.1186/s13024-025-00810-7AgingAstrocyteGliaAstrocyte reactivityNeurodegenerative diseaseLipid droplets
spellingShingle Holly K. Gildea
Shane A. Liddelow
Mechanisms of astrocyte aging in reactivity and disease
Molecular Neurodegeneration
Aging
Astrocyte
Glia
Astrocyte reactivity
Neurodegenerative disease
Lipid droplets
title Mechanisms of astrocyte aging in reactivity and disease
title_full Mechanisms of astrocyte aging in reactivity and disease
title_fullStr Mechanisms of astrocyte aging in reactivity and disease
title_full_unstemmed Mechanisms of astrocyte aging in reactivity and disease
title_short Mechanisms of astrocyte aging in reactivity and disease
title_sort mechanisms of astrocyte aging in reactivity and disease
topic Aging
Astrocyte
Glia
Astrocyte reactivity
Neurodegenerative disease
Lipid droplets
url https://doi.org/10.1186/s13024-025-00810-7
work_keys_str_mv AT hollykgildea mechanismsofastrocyteaginginreactivityanddisease
AT shanealiddelow mechanismsofastrocyteaginginreactivityanddisease