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Cited by 45Neuroinflammation and Neurodegeneration MechanismsGenetics, Aging, and Longevity in Model OrganismsNeuroscience and Neuropharmacology Research

Mechanisms of astrocyte aging in reactivity and disease

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Gildea, Holly K., Liddelow, Shane A.·2025·Molecular Neurodegeneration
DOI 10.1186/s13024-025-00810-7PMC PMC11844071
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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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  • Astrocytes are key regulators of synaptic homeostasis, metabolic support, and neuroinflammation, and are implicated in neurodegenerative disease processes.

    “Astrocytes, as key regulators of synaptic homeostasis, metabolic support, and neuroinflammation, are particularly sensitive to changes in the neuronal environment and have been implicated in numerous neurodegenerative disease processes [112–114].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [112]

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Authors
Gildea, H. K., & Liddelow, S. A.
Affiliations
  • New York University (US)
  • NYU Langone Health (US)
Corresponding author
  • Gildea, Holly K.
  • Liddelow, Shane A.
ORCID
Venue
Molecular Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2025-02-21
Volume
20
Issue
1
Pages
21-21
ISSN
1750-1326 (ISSN-L)
DOI
10.1186/s13024-025-00810-7
PMC
PMC11844071
OpenAlex
W4407774414
Cited by
45
References
24
Citations by year
2026: 28 · 2025: 17
FWCI
4.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute on Aging (K00AG068343)
  • National Eye Institute (R01EY033353)
  • Cure Alzheimer's Fund
  • Gene and Carol Ludwig Family Foundation
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
astrocyte activation, astrocyte heterogeneity, astrocyte senescence, organelle dysfunction, brain homeostasis, neurodegeneration, astrocyte-neuron interaction
MeSH terms
Aging, Animals, Astrocytes, Brain, Humans, Cellular Senescence, Neurodegenerative Diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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