What this means
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.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- People
- Kind of research
- A summary of earlier studies
The science
- Original title
- Histone Modifications at the Intersection of Aging, Neuroinflammation and Metabolism in Alzheimer's Disease.
- Authors
- Liang J, Cao H, Ren X et al.
- Journal
- Aging cell
- Published
- Oct 26, 2026
- Study type
- Review · in humans
- PMID
- 42934178 ↗
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.
Liang J, Cao H, Ren X et al. Histone Modifications at the Intersection of Aging, Neuroinflammation and Metabolism in Alzheimer's Disease. Aging cell. 2026. doi:10.1111/acel.70785. PMID: 42934178. https://pubmed.ncbi.nlm.nih.gov/42934178/