DNA methylation age acceleration mediates the relationship between systemic inflammation and cognitive impairment

Area of Science:

• Gerontology
• Molecular Biology
• Neuroscience

Background:

• Chronic inflammation and DNA methylation are implicated in dementia.
• The interplay between inflammation, DNA methylation age acceleration, and dementia risk is not well understood.

Purpose of the Study:

• To investigate the association between inflammatory cytokines and cognitive impairment.
• To determine if DNA methylation age acceleration mediates the relationship between inflammation and cognitive decline.

Main Methods:

• Utilized data from the Health and Retirement Study (n=3,346, age >50).
• Assessed inflammatory markers (IL-6, CRP, IGF-1) and cognitive status.
• Employed mediation analysis to test the role of DNA methylation age acceleration (GrimAge).

Main Results:

• Higher levels of IL-6, CRP, and IGF-1 were associated with increased odds of cognitive impairment.
• Inflammatory markers were also linked to GrimAge acceleration.
• Mediation analysis revealed that GrimAge acceleration partially explained the association between inflammation and cognitive impairment (e.g., 17.7% for IL-6).

Conclusions:

• Systemic inflammation is significantly associated with cognitive impairment.
• DNA methylation age acceleration appears to be a partial mediator in the pathway from inflammation to cognitive impairment.