The transcription factor Miz1-mediated mechanisms of lung aging

项目概要/摘要 慢性阻塞性肺疾病（COPD）已上升为美国第三大死亡原因， 没有具体有效的治疗方法。年龄是COPD最重要的危险因素。的 导致COPD发病机制的年龄相关变化的机制知之甚少。在这一提议中， 我们将研究Miz 1是否在表观遗传学上抑制衰老相关的NF-κ B依赖性成分， 分泌表型（SASP），其与细胞周期阻滞的抑制合作，以抑制细胞周期的变化。 衰老计划，从而防止COPD的发展。完成本提案，其中包括 动物和人类研究，将提供对COPD发病机制的基本见解， 治疗目标

Project Summary/Abstract Chronic obstructive pulmonary disease (COPD) has risen to the third leading cause of death in the US and specific and effective therapies are not available. Age is the most important risk factor for COPD. The mechanisms of age-related changes that lead to COPD pathogenesis are poorly understood. In this proposal, we will study whether Miz1 epigenetically represses NF-B-dependent components of senescence-associated secretory phenotype (SASP), which acts in cooperation with inhibition of cell cycle arrest to suppress the senescence program, thereby preventing the development of COPD. Completion of this proposal, which includes animal and human studies, will provide fundamental insights into the pathogenesis of COPD and thus provide therapeutic targets.