Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.
Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span.
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DOI：
10.1146/annurev-pharmtox-050120-105018
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发表时间：
2021-01-06
影响因子：
12.5
通讯作者：
Niedernhofer LJ
中科院分区：
文献类型：
--
作者：
Robbins PD;Jurk D;Khosla S;Kirkland JL;LeBrasseur NK;Miller JD;Passos JF;Pignolo RJ;Tchkonia T;Niedernhofer LJ
衰老是应激细胞中激活的信号传导机制的结果，以防止损伤细胞的增殖。衰老细胞（Snc）通常会产生衰老相关的分泌表型以促进免疫清除，这会驱动慢性无菌炎症，并在衰老和年龄相关疾病中发挥因果作用。snc随着年龄的增长和疾病的解剖部位而积累。因此，它们被认为是一个合乎逻辑的治疗目标。Senotherapeutics是一类选择性杀死Snc（senolytics）或抑制其致病表型（senomorphics/senostatics）的新型药物。自2015年以来，一些senolytics从鉴定到临床试验。临床前数据表明，senolytics减轻许多器官的疾病，改善身体功能和恢复力，并抑制所有死亡原因，即使是老年人。在这里，我们回顾了Sncs驱动衰老和疾病的证据，识别和优化senotherapeutics的方法，以及senolytics的临床前和临床测试的现状。
Senescence is the consequence of a signaling mechanism activated in stressed cells to prevent proliferation of cells with damage. Senescent cells (Sncs) often develop a senescence-associated secretory phenotype to prompt immune clearance, which drives chronic sterile inflammation and plays a causal role in aging and age-related diseases. Sncs accumulate with age and at anatomical sites of disease. Thus, they are regarded as a logical therapeutic target. Senotherapeutics are a new class of drugs that selectively kill Sncs (senolytics) or suppress their disease-causing phenotypes (senomorphics/senostatics). Since 2015, several senolytics went from identification to clinical trial. Preclinical data indicate that senolytics alleviate disease in numerous organs, improve physical function and resilience, and suppress all causes of mortality, even if administered to the aged. Here, we review the evidence that Sncs drive aging and disease, the approaches to identify and optimize senotherapeutics, and the current status of preclinical and clinical testing of senolytics.
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影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
通讯作者：
Khosla S
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：
Fuhrmann-Stroissnigg H;Ling YY;Zhao J;McGowan SJ;Zhu Y;Brooks RW;Grassi D;Gregg SQ;Stripay JL;Dorronsoro A;Corbo L;Tang P;Bukata C;Ring N;Giacca M;Li X;Tchkonia T;Kirkland JL;Niedernhofer LJ;Robbins PD
通讯作者：
Robbins PD
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
3.9
作者：
Christopher, Lisa J.;Cui, Donghui;Iyer, Ramaswamy A.
通讯作者：
Iyer, Ramaswamy A.