Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, E1246 BST, 200 Lothrop Street, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Vascular Medicine Institute, Department of Medicine, E1246 BST, 200 Lothrop Street, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Nat Rev Drug Discov. 2017 Nov;16(11):755-772. doi: 10.1038/nrd.2017.170. Epub 2017 Oct 6.
Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches.
特发性肺纤维化（IPF）是一种致命的与年龄相关的疾病，其特征是肺部进行性和不可逆转的瘢痕形成。IPF 的发病机制尚不完全清楚，目前的治疗方法仅限于那些能够降低轻度至中度疾病患者功能下降速度的方法。在这种情况下，迫切需要新的治疗方法，以显著延长这些患者的生存时间和提高生活质量。我们对 IPF 发病机制的了解不完整，以及缺乏能够再现人类疾病关键特征的合适实验模型，这是主要的挑战。由于衰老是 IPF 的一个主要危险因素，因此与年龄相关的细胞扰动，如端粒磨损、衰老、表观遗传漂移、干细胞衰竭、蛋白质稳态丧失和线粒体功能障碍，正在成为 IPF 治疗的靶点。在这篇综述中，我们讨论了目前和新兴的 IPF 治疗方法，特别是那些针对与年龄相关的机制的治疗方法，并讨论了未来的治疗方法。
