Exploring accelerated aging as a target of bipolar disorder treatment: A systematic review

Bipolar disorder (BD) has been linked to accelerated aging processes, with many studies suggesting that drugs used to treat BD may modulate pathways related to aging. This systematic review aimed to determine whether FDA-approved pharmacotherapies for BD have reported effects on aging biomarkers across clinical and preclinical studies. We conducted searches in PubMed and PsychINFO and followed PRISMA guidelines. Out of 6400 records identified, 19 studies met the inclusion criteria. Most preclinical studies tested the effects of BD drugs, especially lithium, on lifespan and telomere biology in cell and animal models. Clinical studies predominantly focused on lithium, evaluating aging markers like telomere length, telomerase, mitochondrial DNA copy number, and epigenetic age acceleration in individuals with BD. Findings indicate that chronic lithium treatment is associated with modulatory effects on aging biomarkers, particularly increased telomere length and telomerase activity. Conversely, some negative results were also reported. Limited evidence suggests potential aging-modulating properties of other mood stabilizers like valproic acid and lamotrigine, evidencing that further investigation is required. Despite variability across studies, the overall findings support the notion that pharmacotherapies used in BD present many effects of aging biomarkers. However, the field is still developing, with a clear emphasis on lithium and a lack of standardized methods to evaluate aging biomarkers in clinical samples. Further research exploring the anti-accelerated aging effects of BD drugs beyond lithium, their mechanisms of action, and potential synergistic effects is warranted.