Abstract
Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity and outcome. In recent years, several lines of evidence have suggested that individuals with MDD have an elevated risk of age-related adverse outcomes across the lifespan. This review provided evidence of a significant overlap between the biological abnormalities in MDD and biological changes commonly observed during the aging process (i.e., hallmarks of biological aging). Based on such evidence, we formulate a mechanistic model showing how abnormalities in the hallmarks of biological aging can be a common denominator and mediate the elevated risk of age-related health outcomes commonly observed in MDD. Finally, we proposed a roadmap for novel studies to investigate the intersection between the biology of aging and MDD, including the use of geroscience-guided interventions, such as senolytics, to delay or improve major depression by targeting biological aging.