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

加速衰老的机制：压力、健康行为和线粒体的作用

• 批准号: 10592895
• 负责人: AUDREY TYRKA
• 金额: $ 22.42万
• 依托单位: BUTLER HOSPITAL (PROVIDENCE, RI)
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592895
• 关键词: Acceleration; Acute; Adult; Age; Aging; Animal Model; Animals; Anxiety Disorders; Atherosclerosis; Attention; Behavior; Behavioral; Biological; Cardiovascular Diseases; Cell Aging; Cell Death; Child Abuse and Neglect; Childhood; Complex; DNA copy number; Data; Depressive disorder; Diabetes Mellitus; Diet; Disease; Early-life trauma; Enzymes; Epigenetic Process; Exercise; Fasting; Glucocorticoids; Health; Health behavior; Health behavior and outcomes; Human; Hydrocortisone; Impairment; Individual; Inflammation; Inflammatory; Insulin Resistance; Intervention; Interview; Laboratories; Leukocytes; Link; Lipids; Measures; Mental disorders; Metabolic Pathway; Metabolic syndrome; Mitochondria; Mitochondrial DNA; Molecular; Neurosecretory Systems; Obesity; Outcome; Oxidative Stress; Pain; Pathway interactions; Pharmaceutical Preparations; Physical activity; Play; Premature aging syndrome; Prevention approach; Process; Proteins; Public Health; Reactive Oxygen Species; Recording of previous events; Respiration; Risk; Risk Factors; Role; Sampling; Signal Pathway; Signal Transduction; Signs and Symptoms; Sleep; Smoking; Specimen; Specimen Handling; Stress; Stroke; Symptoms; Syndrome; Testing; Time; Trauma; Unhealthy Diet; Weight; Work; age related; anxiety symptoms; biological adaptation to stress; childhood adversity; depressive symptoms; disorder risk; early experience; early life adversity; follow-up; indexing; insight; metabolic rate; novel; pediatric trauma; poor health outcome; poor sleep; prospective; psychiatric symptom; sedentary lifestyle; stressor; trauma exposure; vaping

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.

早期逆境，包括儿童虐待和其他创伤，是许多人的主要危险因素 与衰老有关的疾病，包括心血管疾病，中风，疼痛综合征和糖尿病。健康 饮食和久坐不良的生活方式以及成人压力源等行为与儿童逆境有关 进一步促进了这些疾病的风险。随着时间的流逝，这些影响的复合和健康结果不佳 当压力和健康行为的生物学作用与年龄相关的下降相结合时，在成年人中最明显 产生坦率的疾病。现在有大量证据表明糖皮质激素和炎症机制 在早期逆境之后加速衰老并赋予疾病风险。来自动物的融合证据 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，可能是这些压力和年龄相关的风险机制 疾病。人类最近的工作牵涉到线粒体的早期创伤对风险的影响 精神疾病。我们的实验室表明，线粒体DNA拷贝数（mtdnaCn）在 具有儿童创伤病史的健康成年人的白细胞以及抑郁症和焦虑的人 疾病。其他最新研究的结果表明，应力与线粒体的改变有关 酶和线粒体呼吸受损。饮食，运动和睡眠等健康行为可能是 随着早期逆境的改变，并在早期逆境对分子和健康的影响中起重要作用 结局表示加速衰老。拟议的研究利用了一个可用的数据和标本 研究儿童虐待的研究，包括有关暴露，健康行为，生物标本的丰富数据， 和健康结果。这项研究的结果有望提供有关生物学机制的见解 与逆境有关的风险加速衰老和疾病风险，并为新治疗和 预防方法。