a Chair of Respiratory Medicine, Department of Experimental Medicine and Surgery , University of Rome "Tor Vergata" , Rome , Italy.
b Unit of Pharmacology, Department of Experimental Medicine , University of Campania "Luigi Vanvitelli" , Naples , Italy.
Expert Opin Investig Drugs. 2018 Jul;27(7):573-581. doi: 10.1080/13543784.2018.1492548. Epub 2018 Jul 4.
Aging is the major risk factor for most of the chronic diseases. Cellular senescence is one of the main hallmarks of aging. A growing body of evidence implicates accelerated mechanisms of aging, including cellular senescence, in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) pathogenesis. Senolytics are pharmaceutical agents that eliminate senescent cells, thus blocking tissue degeneration and late life complications and allowing tissue regeneration.
The potential use of senolytic drugs in respiratory medicine is examined and discussed.
The promising signal generated by preclinical studies supports proof-of-principle clinical studies with senolytic agents in the treatment of IPF, but this signal is not very strong, and furthermore, senolytic drugs could be detrimental in IPF patients. On the other hand, the preclinical evidence that these agents are able to influence the natural history of COPD is still lacking. COPD is a very heterogeneous lung disease presenting different (mixed) phenotypes. Given the difference in underlying pathology of these phenotypes, it can be envisaged that lung aging is more or differently involved in some of these phenotypes than others. Consequently, it will be difficult to determine which COPD patient will benefit from a treatment with senolytics.
衰老 是大多数慢性疾病的主要风险因素。细胞衰老 是衰老的主要标志之一。越来越多的证据表明,包括细胞衰老在内的加速衰老机制与特发性肺纤维化 (IPF) 和慢性阻塞性肺疾病 (COPD) 的发病机制有关。衰老细胞清除剂是一种能消除衰老细胞的药物,从而阻止组织退化和晚年并发症,并允许组织再生。
检查并讨论了呼吸医学中使用衰老细胞清除剂的潜力。
临床前研究产生的有希望的信号支持使用衰老细胞清除剂治疗 IPF 的原理验证临床研究,但该信号不是很强,此外,衰老细胞清除剂可能对 IPF 患者有害。另一方面,这些药物能够影响 COPD 自然病史的临床前证据仍然缺乏。COPD 是一种非常异质的肺部疾病,表现出不同的(混合)表型。鉴于这些表型的潜在病理差异,可以想象,在某些表型中,肺部衰老的参与程度更大或不同。因此,很难确定哪些 COPD 患者将从衰老细胞清除剂的治疗中受益。