Epigenetic noise in the aging brain: tuning neuronal vulnerability to neurodegeneration.

Xinyang Yin, Houchun Zhang, Ru Zhang, Jianhuang Xue, Yujun Hou

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Tongji Hospital Affiliated to Tongji University, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. · pubmed

Paper

Abstract

Aging is the predominant risk factor for neurodegenerative diseases, yet the mechanisms linking biological aging to selective neuronal degeneration remain incompletely understood. Accumulating evidence indicates that aging progressively disrupts epigenetic regulation, manifested as increased epigenetic noise in DNA methylation, histone modifications, and chromatin accessibility, which undermines transcriptional precision and the stability of neuronal identity. Recent advances in single-cell and spatial epigenomics further suggest that these age-associated epigenetic alterations are not merely correlative but can actively shape neuronal vulnerability across brain regions and cell types. In this review, we synthesize emerging evidence showing how epigenetic noise contributes to selective neurodegeneration across Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, and discuss emerging strategies aimed at stabilizing the aging neuronal epigenome.

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Research summary

Increased epigenetic noise in the aging brain contributes to selective neurodegeneration across various diseases. The paper addresses the mechanisms linking biological aging to neuronal vulnerability, which is crucial for understanding and potentially mitigating age-related neurodegenerative diseases.

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