A wise man once said that time is relative, and while physics was on his mind, it seems that biology should have been as well. For instance, patients with bipolar disorder suffer from accelerated aging. However, examinations of telomere length have given mixed results, and this inspired the lab of Joao Quevedo in the University of Texas Health Science Center at Houston to set their gaze on the epigenetic clock and mitochondrial DNA copy number.
The group recruited 22 patients with bipolar disorder, 16 of their siblings, and 20 matched controls and examined their peripheral blood. In addition to analyzing the epigenetic clock via the 450k DNA methylation array, the group also interrogated other biological clocks (telomere length and mitochondrial DNA copy number) via qPCR.
Here’s what they discovered:
- Older (>33 years old) bipolar disorder patients display both accelerated epigenetic aging and increased mitochondrial DNA copy number
- However, they did not observe the same pattern in younger patients
- Epigenetic age correlates with mitochondrial DNA copy number in older patients
- Telomere length shows no significant difference in bipolar patients
- Telomere length also shows no correlation with the two other biological clocks
Epigenetic Clock Cross-Talk
First author Gabriel Fries shares, “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.” Interestingly, this correlation may arise with a little help from the 5% (17 of 353) of the epigenetic clock’s CpGs that map to nuclear-encoded mitochondrial genes.
However, the mechanistic potential doesn’t end there. 24% (85) of the epigenetic clock’s CpGs locate to glucocorticoid response elements, which are critical to stress response. Fries concludes, “We believe a difference wasn’t detected in younger patients because they haven’t had as much exposure to stressful events. 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.”
Catch all the epigenetic cross-talk over at Translational Psychiatry, December 2017