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

早期生活逆境，包括童年虐待和其他创伤，是许多人的主要风险因素 与衰老相关的病症，包括心血管疾病、中风、疼痛综合征和糖尿病。健康 行为，如不良的饮食和久坐不动的生活方式，以及成年后的压力源，与儿童时期的逆境有关， 进一步增加这些疾病的风险。这些影响随着时间的推移而加剧， 当压力和健康行为的生物学效应与年龄相关的衰退联合收割机时， 导致弗兰克病现在有大量的证据表明糖皮质激素和炎症机制 加速衰老并在早期逆境后增加疾病风险。来自动物的证据 模型和最近的人类研究表明，线粒体在协调压力方面起着关键作用， 反应和在老化过程中，并可能是一种机制的风险，这些压力和年龄有关的 紊乱最近的人类研究表明，线粒体与早期创伤对以下风险的影响有关： 精神疾病我们的实验室表明，线粒体DNA拷贝数（mtDNA）增加， 有童年创伤史的健康成人以及抑郁和焦虑患者的白细胞 紊乱其他最近的研究结果表明，压力与线粒体的改变有关， 酶和受损的线粒体呼吸。健康行为，如饮食，运动和睡眠，可能是 并在早期逆境对分子和健康的影响中发挥重要作用 结果表明加速老化。拟议的研究利用了一个 研究儿童期虐待，包括关于暴露、健康行为、生物标本 和健康结果。这项研究的结果有望提供深入了解的生物学机制， 加速衰老的不良相关风险和疾病风险，并为新的治疗提供目标， 预防方法。

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.