Bipolar Disorder May Involve Accelerated Epigenetic Aging

Bipolar disorder could involve faster epigenetic aging, which may explain why persons with the disorder are more likely to have – and die from – age-related diseases, a new study from researchers from The University of Texas Health Science Center at Houston found.

Chronological age is measured in the amount of time that a person has been alive, but epigenetic age measures molecular markers of chemical modifications to DNA.

“Bipolar disorder has been previously associated with accelerated aging but the mechanisms are largely unknown. We aimed to understand from our study the biology of what’s driving the accelerated aging. What we found is that patients with bipolar disorder showed an accelerated epigenetic aging compared to healthy controls,”

said first author Gabriel R. Fries, Ph.D., post-doctoral research fellow in the Department of Psychiatry and Behavioral Sciences at McGovern Medical School at UTHealth.

Precipitating Factors

The chemical modifications could be precipitated by the disorder itself or by poor lifestyle habits in diet, exercise, tobacco use and illegal substance use.

“Controlling these factors is just as important as taking medications,”

Fries said.

Using blood samples, the researchers compared 22 patients with bipolar disorder, 16 siblings of bipolar patients and 20 healthy controls.

DNA methylation age

Scatterplot illustrating the significant and positive correlation between DNA methylation age (DNAm age in years, calculated based on the Horvath algorithm) and chronological age (years).
Credit: Gabriel R. Fries, et al. CC-BY

They also found that while older bipolar disorder patients had significantly accelerated epigenetic aging compared to controls, no difference was found in younger patients.

“We believe a difference wasn’t detected in younger patients because they haven’t had as much exposure to stressful events,” Fries said. “This gave us a hint that cumulative chronic exposure to stress would relate to accelerated aging. We would see it more in older people who have experienced a lifetime of stress in dealing with the disease.”

Other Biological Clocks

Along with the epigenetic clock, the study included two other biologic clocks: telomere length and mitochondrial DNA copy numbers. Aging has been consistently associated with a progressive dysfunction in respiratory chain activity and cumulative mitochondrial dysfunction 27.

“The epigenetic acceleration correlated with the number of copies of mitochondrial DNA, suggesting that the cross-talk between the nucleus and the mitochondria might be underlying the premature aging in bipolar disorder,”

Fries said.

Bipolar disorder is an often severe and highly disabling psychiatric condition that affects around 1% of the population,  and has been characterized by many features of aging that can complicate disease outcomes and converge to premature aging (commonly described as accelerated aging in the field).

Gabriel R. Fries, Isabelle E. Bauer, Giselli Scaini, Mon-Ju Wu, Iram F. Kazimi, Samira S. Valvassori, Giovana Zunta-Soares, Consuelo Walss-Bass, Jair C. Soares & Joao Quevedo
Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder
Translational Psychiatry 7, Article number: 1283 (2017) doi:10.1038/s41398-017-0048-8

Top Image: Michael Northrop, Wellcome Images