Senotherapeutics: Targeting senescence in idiopathic pulmonary fibrosis.
Senotherapeutics: Targeting senescence in idiopathic pulmonary fibrosis.
复制标题
衰老疗法：针对特发性肺纤维化中的细胞衰老 。
DOI：
10.1016/j.semcdb.2019.12.008
复制
发表时间：
2020-05
影响因子：
7.3
通讯作者：
Lagares D
中科院分区：
文献类型：
--
作者：
Merkt W;Bueno M;Mora AL;Lagares D
特发性肺纤维化（IPF）是一种致命的慢性肺部疾病，其特征是肺组织进行性瘢痕形成，导致呼吸衰竭。IPF无法治愈，目前的抗纤维化治疗可适度阻止其进一步进展。IPF患病率和发病率随年龄增加而增加，这是一个公认的风险因素。过去15年的密集临床和基础研究表明，IPF患者的肺部存在加速老化的标志。IPF肺中的不同细胞类型表现出过早的衰老特征，包括端粒磨损和细胞衰老。在这篇综述中，我们讨论了最近对这些年龄相关变化背后的机制及其对肺纤维化发展的贡献的见解。我们专注于肺泡II型上皮细胞端粒磨损的遗传和分子基础，促进细胞衰老和肺纤维化。从机制上讲，衰老细胞分泌促纤维化因子，激活瘢痕形成肌成纤维细胞。最终，衰老的肺泡上皮细胞失去其再生能力，阻碍纤维化的解决。此外，线粒体功能障碍与IPF中衰老上皮细胞和衰老肌成纤维细胞的出现密切相关，这些细胞通过适应其代谢途径并对细胞凋亡产生抗性而持续存在于纤维化组织中。我们讨论了通过所谓的衰老治疗药物靶向细胞衰老来治疗IPF的新兴新型治疗策略。
Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease characterized by progressive scarring of the lung tissue, leading to respiratory failure. There is no cure for IPF, and current anti-fibrotic treatments modestly arrest its further progression. IPF prevalence and incidence increase with age, which is a recognized risk factor. Intense clinical and basic research over the last fifteen years has shown that hallmarks of accelerated aging are present in the lungs of patients with IPF. Different cell types in IPF lungs exhibit premature hallmarks of aging, including telomere attrition and cellular senescence. In this Review, we discuss recent insights into the mechanisms behind these age-related alterations and their contribution to the development of lung fibrosis. We focus on the genetic and molecular basis of telomere attrition in alveolar type II epithelial cells, which promote cellular senescence and lung fibrosis. Mechanistically, senescent cells secrete pro-fibrotic factors that activate scar-forming myofibroblasts. Ultimately, senescent alveolar epithelial cells lose their regenerative capacity, impeding fibrosis resolution. In addition, mitochondrial dysfunction is strongly associated with the appearance of senescent epithelial cells and senescent myofibroblasts in IPF, which persist in the fibrotic tissue by adapting their metabolic pathways and becoming resistant to apoptosis. We discuss emerging novel therapeutic strategies to treat IPF by targeting cellular senescence with the so-called senotherapeutics.
登录
查看更多内容
影响因子：
30.8
作者：
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
3.1
作者：
Choi WI;Dauti S;Kim HJ;Park SH;Park JS;Lee CW
通讯作者：
Lee CW
影响因子：
3.7
作者：
Bueno, Marta;Zank, Daniel;Mora, Ana L.
通讯作者：
Mora, Ana L.
影响因子：
4.4
作者：
Diamantopoulos A;Wright E;Vlahopoulou K;Cornic L;Schoof N;Maher TM
通讯作者：
Maher TM
影响因子：
3.7
作者：
Coluzzi E;Colamartino M;Cozzi R;Leone S;Meneghini C;O'Callaghan N;Sgura A
通讯作者：
Sgura A