Mechanisms of Accelerated Aging: Stress, Health Behaviors, and the Role of Mitochondria

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Early life adversity, including childhood maltreatment and other traumas, is a major risk factor for a host of aging-related conditions, including cardiovascular disease, stroke, pain syndromes, and diabetes. Health behaviors, such as poor diet and sedentary lifestyle, and adult stressors, are linked to childhood adversity and further contribute to risk for these diseases. These effects compound over time and poor health outcomes are most evident in adults when biological effects of stress and health behaviors combine with age-related decline to produce frank disease. There is now substantial evidence of glucocorticoid and inflammatory mechanisms that accelerate aging and confer risk for disease following early adversity. Converging evidence from animal models and recent human studies indicate that mitochondria play a key role in coordinating the stress response and in the aging process, and may be a mechanism of risk for these stress- and age-related disorders. Recent work in humans has implicated mitochondria in the effect of early trauma on risk for psychiatric disorders. Our laboratory showed that mitochondrial DNA copy number (mtDNAcn) is increased in leukocytes of healthy adults with a history of childhood trauma, as well as those with depressive and anxiety disorders. Results of other recent studies suggest that stress is linked with alterations of mitochondrial enzymes and impaired mitochondrial respiration. Health behaviors, such as diet, exercise, and sleep, may be altered with early adversity and play an important role in the effects of early adversity on molecular and health outcomes indicative of accelerated aging. The proposed study leverages data and specimens available in a study of childhood maltreatment that includes rich data on exposures, health behaviors, biological specimens, and health outcomes. Results of this study are expected to provide insight into the biological mechanisms of adversity-related risk for accelerated aging and risk for disease, and provide targets for new treatment and prevention approaches.