Newcastle University Institute for Ageing, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom.
National Heart & Lung Institute, Imperial College, London SW3 6LY, United Kingdom.
Pharmacol Ther. 2018 Mar;183:34-49. doi: 10.1016/j.pharmthera.2017.10.005. Epub 2017 Oct 4.
Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP). The roles of telomeres, the mitochondria and cellular senescence in lung ageing and disease are discussed. Therapeutic interventions targeting cellular senescence are considered for delaying or potentially reversing age-related respiratory disease.
细胞衰老,即体细胞复制能力的不可逆转丧失,在与年龄相关的病理学发展和许多与年龄相关的慢性炎症性疾病中起着因果作用。衰老的肺部有越来越多的衰老细胞,越来越多的证据表明,衰老可能直接导致许多与年龄相关的呼吸疾病,包括慢性阻塞性肺疾病(COPD)和特发性肺纤维化(IPF)。端粒功能障碍和线粒体动态平衡的改变在细胞衰老中经常发生,对于衰老相关分泌表型(SASP)的发展非常重要。端粒、线粒体和细胞衰老在肺部衰老和疾病中的作用也在讨论之中。针对细胞衰老的治疗干预措施被认为可以延缓或潜在地逆转与年龄相关的呼吸疾病。