Accelerated aging in bipolar disorder: A comprehensive review of molecular findings and their clinical implications

Bipolar disorder (BD) has been associated with clinical signs of accelerated aging, which potentially underlies its association with several age-related medical conditions, such as hypertension, metabolic imbalances, dementia, and cancer. This paper aims to comprehensively review evidence of biological aging in BD and explore findings and controversies related to common biological clocks in patients, including telomere length, DNA methylation, mitochondrial DNA copy number, inflammation, and oxidative stress. Our results suggest a complex interplay between biological markers and a potential key role of environmental factors, such as childhood trauma and psychological stress, in determining premature aging in patients. Moreover, given its multifactorial nature, our summary evidences the need for further studies incorporating clinical evidence with biomarkers of accelerated aging in BD. Results of this review strongly suggest BD as an accelerated aging disease seen in both clinical and molecular aspects. Understanding the pathophysiology of aging in BD may ultimately lead to identification of pathways that can be targeted for prevention of premature aging in patients and early onset of aging-related conditions.