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Peer-reviewedCC BY 4.0Aging Cell

Histone Modifications at the Intersection of Aging, Neuroinflammation and Metabolism in Alzheimer's Disease

  • Junyi Liang1
  • Huawen Cao1
  • Xiumin Ren2
  • Nan Sha1
  • Xueqing Han1
  • Ling Jiang1
  • Bin Liu1
  • Weiming Zhao1
  1. 1Heilongjiang University of Chinese Medicine Harbin Heilongjiang Province China
  2. 2The First Affiliated Hospital of Jiamusi University Jiamusi Heilongjiang Province China
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Abstract

Aging, neuroinflammation and metabolic dysfunction are tightly intertwined in Alzheimer's disease (AD), but how transient pathological signals become persistent cellular states remains poorly understood. Histone post‐translational modifications (PTMs) provide a dynamic interface between extracellular stimuli, cellular metabolism and chromatin state. This Review examines how canonical histone modifications and emerging metabolite‐derived acylations regulate inflammatory and stress‐responsive programmes across microglia, astrocytes and neurons during aging and AD. We discuss how amyloid‐β, tau pathology, metabolic dysfunction and innate immune signaling converge on histone‐modifying machinery, and how reciprocal interactions between metabolism and chromatin may stabilize disease‐associated cell states. Particular attention is given to cellular senescence and neuroimmune memory, while emphasizing the context dependence of individual histone marks across cell types, genomic regions and disease stages. We further evaluate evidence for causality using three criteria: perturbation, persistence and reversibility. This framework distinguishes chromatin states that accompany ongoing pathology from those capable of sustaining pathological cell states beyond their initiating signals. Finally, we consider therapeutic strategies targeting histone‐modifying enzymes, chromatin readers and metabolic inputs to restore chromatin plasticity and promote resolution of chronic neuroinflammation.

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Cite

BibTeXRIS
BibTeX
@article{liang2026histone,
  title = {{Histone Modifications at the Intersection of Aging, Neuroinflammation and Metabolism in Alzheimer's Disease}},
  author = {Junyi Liang and Huawen Cao and Xiumin Ren and Nan Sha and Xueqing Han and Ling Jiang and Bin Liu and Weiming Zhao},
  journal = {Aging Cell},
  year = {2026},
  month = oct,
  doi = {10.1111/acel.70785},
  url = {https://doi.org/10.1111/acel.70785},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Histone Modifications at the Intersection of Aging, Neuroinflammation and Metabolism in Alzheimer's Disease
AU  - Junyi Liang
AU  - Huawen Cao
AU  - Xiumin Ren
AU  - Nan Sha
AU  - Xueqing Han
AU  - Ling Jiang
AU  - Bin Liu
AU  - Weiming Zhao
PY  - 2026
DA  - 2026/10/26
JO  - Aging Cell
DO  - 10.1111/acel.70785
UR  - https://doi.org/10.1111/acel.70785
AB  - Aging, neuroinflammation and metabolic dysfunction are tightly intertwined in Alzheimer's disease (AD), but how transient pathological signals become persistent cellular states remains poorly understood. Histone post‐translational modifications (PTMs) provide a dynamic interface between extracellular stimuli, cellular metabolism and chromatin state. This Review examines how canonical histone modifications and emerging metabolite‐derived acylations regulate inflammatory and stress‐responsive programmes across microglia, astrocytes and neurons during aging and AD. We discuss how amyloid‐β, tau pathology, metabolic dysfunction and innate immune signaling converge on histone‐modifying machinery, and how reciprocal interactions between metabolism and chromatin may stabilize disease‐associated cell states. Particular attention is given to cellular senescence and neuroimmune memory, while emphasizing the context dependence of individual histone marks across cell types, genomic regions and disease stages. We further evaluate evidence for causality using three criteria: perturbation, persistence and reversibility. This framework distinguishes chromatin states that accompany ongoing pathology from those capable of sustaining pathological cell states beyond their initiating signals. Finally, we consider therapeutic strategies targeting histone‐modifying enzymes, chromatin readers and metabolic inputs to restore chromatin plasticity and promote resolution of chronic neuroinflammation.
SN  - 1474-9718
SN  - 1474-9726
ER  -