Accelerated hippocampal biological aging in bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Aging Research

Background:

• Bipolar disorder (BD) is associated with accelerated aging mechanisms, including DNA methylation (DNAm) aging in blood.
• It remains unclear if these aging mechanisms are present in the brain and interact with other biological clocks.

Purpose of the Study:

• To investigate genome-wide DNA methylation (DNAm) and other biological aging markers in the postmortem hippocampus of individuals with BD compared to controls.
• To explore the association between epigenetic aging, telomere length (TL), and mitochondrial DNA (mtDNA) copy number in the BD brain.

Main Methods:

• Genome-wide DNA methylation (DNAm) was analyzed in postmortem hippocampus samples from 32 BD-I patients and 32 controls.
• Epigenetic aging acceleration was calculated using the Horvath method.
• Telomere length (TL) and mitochondrial DNA (mtDNA) copy number were quantified, and analyses controlled for age, sex, and other relevant covariates.

Main Results:

• No overall difference in epigenetic aging acceleration was found between groups.
• Older BD patients exhibited significant epigenetic aging acceleration compared to controls (P = .042).
• A reduction in mtDNA copy number was observed in BD patients (P = .047), with no difference in TL. Significant correlations were found between epigenetic aging acceleration, TL, and mtDNA copy number.

Conclusions:

• Hippocampal aging may contribute to neurocognitive deficits in bipolar disorder (BD).
• The findings suggest a complex interplay between biological clocks in the hippocampus, potentially explaining premature aging manifestations in BD.