1 Aging Institute.
2 Division of Pulmonary Allergy and Critical Care Medicine, and.
Am J Respir Cell Mol Biol. 2019 Jul;61(1):21-30. doi: 10.1165/rcmb.2018-0410TR.
Senescence is a cell fate decision characterized by irreversible arrest of proliferation accompanied by a senescence-associated secretory phenotype. Traditionally, cellular senescence has been recognized as a beneficial physiological mechanism during development and wound healing and in tumor suppression. However, in recent years, evidence of negative consequences of cellular senescence has emerged, illuminating its role in several chronic pathologies. In this context, senescent cells persist or accumulate and have detrimental consequences. In this review, we discuss the possibility that in chronic obstructive pulmonary disease, persistent senescence impairs wound healing in the lung caused by secretion of proinflammatory senescence-associated secretory phenotype factors and exhaustion of progenitor cells. In contrast, in idiopathic pulmonary fibrosis, chronic senescence in alveolar epithelial cells exacerbates the accumulation of senescent fibroblasts together with production of extracellular matrix. We review how cellular senescence may contribute to lung disease pathology.
衰老(senescence)是一种细胞命运决定,其特征是不可逆的增殖停滞,并伴有衰老相关分泌表型(senescence-associated secretory phenotype)。传统上,细胞衰老被认为是发育和伤口愈合以及肿瘤抑制过程中的一种有益的生理机制。然而,近年来,细胞衰老的负面后果的证据已经出现,这阐明了其在几种慢性病理中的作用。在这种情况下,衰老细胞持续存在或积累,并产生有害的后果。在这篇综述中,我们讨论了在慢性阻塞性肺疾病(chronic obstructive pulmonary disease)中,持续的衰老通过分泌促炎的衰老相关分泌表型因子和祖细胞耗竭,损害肺部的伤口愈合的可能性。相比之下,在特发性肺纤维化(idiopathic pulmonary fibrosis)中,肺泡上皮细胞的慢性衰老加剧了衰老成纤维细胞的积累以及细胞外基质的产生。我们回顾了细胞衰老如何导致肺部疾病的病理变化。