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

早年的逆境，包括童年时期的虐待和其他创伤，是许多 与衰老相关的疾病，包括心血管疾病、中风、疼痛综合征和糖尿病。健康状况 不良饮食和久坐不动的生活方式等行为，以及成年后的压力源，与儿童时期的逆境和 进一步增加了这些疾病的风险。随着时间的推移，这些影响会加剧，并导致不良的健康结果 当压力和健康行为的生物效应与年龄相关的衰退结合在一起时，在成年人中最为明显 制造弗兰克病。现在有大量证据表明糖皮质激素和炎症机制。 这会加速衰老，并增加早期逆境后患病的风险。汇聚来自动物的证据 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。 反应和衰老过程中，这可能是这些应激和年龄相关的风险机制 精神错乱。最近在人类中的研究表明，线粒体与早期创伤对高血压风险的影响有关。 精神障碍。我们的实验室发现线粒体DNA拷贝数(MtDNAcn)在 有童年创伤史的健康成年人以及抑郁症和焦虑症患者的白细胞 精神错乱。最近的其他研究结果表明，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、锻炼和睡眠，可能是 在早期逆境对分子和健康的影响中起重要作用 结果表明衰老加速。拟议的研究利用了可在 关于儿童期虐待的研究，包括关于接触、健康行为、生物标本、 和健康结果。这项研究的结果有望为深入了解心力衰竭的生物学机制提供帮助。 与逆境相关的加速衰老风险和疾病风险，并为新的治疗和 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.