Cellular Senescence: A Translational Perspective.
Cellular Senescence: A Translational Perspective.
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DOI：
10.1016/j.ebiom.2017.04.013
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发表时间：
2017-07
期刊：
影响因子：
11.1
通讯作者：
Tchkonia T
中科院分区：
文献类型：
--
作者：
Kirkland JL;Tchkonia T
细胞衰老需要基本上不可逆的复制停滞，凋亡抗性，并经常获得促炎性，组织破坏性衰老相关分泌表型（SASP）。衰老细胞随着衰老在各种组织中积累，并在许多慢性疾病和病症的发病部位积累。SASP可导致衰老相关炎症、代谢失调、干细胞功能障碍、衰老表型、慢性疾病、老年综合征和恢复力丧失。延迟衰老细胞积累或减少衰老细胞负荷与延迟、预防或减轻多种衰老相关病症相关。我们使用假设驱动的方法来发现促存活衰老细胞抗凋亡通路（SCAPs），并基于这些SCAPs，发现第一种衰老清除剂，即导致衰老细胞对其自身促凋亡微环境敏感的药物。在临床前模型中似乎可以减轻多种衰老相关表型的几种衰老清除剂正在开始转化为可能具有变革性的临床干预措施。细胞衰老是慢性疾病、恢复力丧失和老年综合征的衰老过程之一。Senolytics选择性诱导衰老细胞凋亡。它们在临床前研究中延迟或减轻多种疾病。如果senolytics在临床试验中被证明是有效和安全的，它们可能是变革性的。
Cellular senescence entails essentially irreversible replicative arrest, apoptosis resistance, and frequently acquisition of a pro-inflammatory, tissue-destructive senescence-associated secretory phenotype (SASP). Senescent cells accumulate in various tissues with aging and at sites of pathogenesis in many chronic diseases and conditions. The SASP can contribute to senescence-related inflammation, metabolic dysregulation, stem cell dysfunction, aging phenotypes, chronic diseases, geriatric syndromes, and loss of resilience. Delaying senescent cell accumulation or reducing senescent cell burden is associated with delay, prevention, or alleviation of multiple senescence-associated conditions. We used a hypothesis-driven approach to discover pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) and, based on these SCAPs, the first senolytic agents, drugs that cause senescent cells to become susceptible to their own pro-apoptotic microenvironment. Several senolytic agents, which appear to alleviate multiple senescence-related phenotypes in pre-clinical models, are beginning the process of being translated into clinical interventions that could be transformative. Cellular senescence is among the aging processes underlying chronic diseases, loss of resilience, and geriatric syndromes. Senolytics selectively induce senescent cell apoptosis. They delay or alleviate multiple disorders in preclinical studies. If senolytics are demonstrated to be effective and safe in clinical trials, they could be transformative.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
16.6
作者：
Jurk, Diana;Wilson, Caroline;Passos, Joao F.;Oakley, Fiona;Correia-Melo, Clara;Greaves, Laura;Saretzki, Gabriele;Fox, Chris;Lawless, Conor;Anderson, Rhys;Hewitt, Graeme;Pender, Sylvia L. F.;Fullard, Nicola;Nelson, Glyn;Mann, Jelena;van de Sluis, Bart;Mann, Derek A.;von Zglinicki, Thomas
通讯作者：
von Zglinicki, Thomas
影响因子：
11.8
作者：
Demaria, Marco;Ohtani, Naoko;Youssef, Sameh A.;Rodier, Francis;Toussaint, Wendy;Mitchell, James R.;Laberge, Remi-Martin;Vijg, Jan;Van Steeg, Harry;Dolle, Martijn E. T.;Hoeijmakers, Jan H. J.;de Bruin, Alain;Hara, Eiji;Campisi, Judith
通讯作者：
Campisi, Judith
影响因子：
3.9
作者：
Kirkland, James L.
通讯作者：
Kirkland, James L.
影响因子：
82.9
作者：
Chang J;Wang Y;Shao L;Laberge RM;Demaria M;Campisi J;Janakiraman K;Sharpless NE;Ding S;Feng W;Luo Y;Wang X;Aykin-Burns N;Krager K;Ponnappan U;Hauer-Jensen M;Meng A;Zhou D
通讯作者：
Zhou D