DNA Methylation in Aging and Alzheimer’s Disease

TL;DR

This paper reviews how DNA methylation changes with age and contributes to Alzheimer’s disease, highlighting key challenges and future research directions.

Contribution

The paper systematically reviews current knowledge and unresolved issues in DNA methylation related to aging and Alzheimer’s disease.

Findings

Age-related DNA methylation changes disrupt cellular processes like inflammation and proteostasis linked to Alzheimer’s.

Global hypomethylation in repetitive elements and gene-specific changes are associated with neurodegeneration.

Inconsistencies across brain regions and limited understanding of cell-type specificity hinder progress in the field.

Abstract

DNA methylation undergoes significant changes with age. These alterations play a pivotal role in the development of age-related diseases, including Alzheimer’s disease (AD). Recent advancements in DNA methylome profiling have revealed global hypomethylation patterns, particularly within repetitive elements, as well as gene-specific changes that are associated with neurodegeneration. Age-related alterations in DNA methylation have been implicated in the disruption of key cellular processes, such as inflammation and proteostasis, both central to AD pathology. However, several challenges persist in this field. One major issue is the inconsistency of findings across different brain regions and tissue types, which complicates result interpretation. Furthermore, the limited understanding of cell-type specificity raises concerns about the generalizability of findings from bulk tissue analyses. Key questions remain in DNA methylation research related to aging and AD, including elucidating the precise mechanisms driving methylation changes, exploring cell-type specificity, determining the functional consequences of these alterations, and investigating cross-tissue correlations. A deeper understanding of the spatiotemporal dynamics of methylation changes, the underlying mechanisms, and their therapeutic implications is essential to the development of novel prevention and treatment strategies. This review will delve into these findings and challenges, offering insights into future research directions.

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