Division of Pulmonary, Allergy and Critical Care and Sleep Medicine, University of Arizona , Tucson, Arizona and Southern Arizona Veterans Affairs Health Care System, Tucson, Arizona.
Am J Physiol Lung Cell Mol Physiol. 2018 Apr 1;314(4):L642-L653. doi: 10.1152/ajplung.00275.2017. Epub 2017 Dec 14.
The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.
人口老龄化的迅速扩张导致了与年龄相关的疾病的流行,包括慢性和急性肺部疾病的发病率和死亡率上升。大量研究表明,衰老和氧化应激与各种肺部疾病的发病机制有关;然而,尽管这些领域最近取得了进展,但衰老和氧化应激的具体贡献仍不清楚。这篇综述将讨论衰老对肺部形态和生理学的影响,以及氧化还原失衡与衰老如何导致肺部疾病易感性。在这里,我们重点关注三种衰老为重要危险因素的肺部疾病:急性呼吸窘迫综合征(ARDS)、慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)。讨论了针对氧化还原和衰老改变的治疗策略的临床前和临床进展,以及可能指导当前和未来治疗开发的科学进展。更深入地了解衰老如何影响正常肺功能、氧化还原平衡和损伤修复过程,将激发新疗法的开发,以预防和/或逆转与年龄相关的肺部疾病,并最终延长健康寿命。这篇综述旨在鼓励基础、临床和转化研究,弥合衰老、氧化应激和肺部疾病交叉点的知识差距,为治疗老年人中发病率较高的肺部疾病提供更有效的治疗策略。
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