Strategies for Targeting Senescent Cells in Human Disease.
Strategies for Targeting Senescent Cells in Human Disease.
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DOI：
10.1038/s43587-021-00121-8
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Xu M
中科院分区：
文献类型：
--
作者：
Gasek NS;Kuchel GA;Kirkland JL;Xu M
细胞衰老代表了一种独特的细胞命运，其特征是对一系列外在和内在应激反应的复制停滞。衰老在发育和伤口愈合过程中提供编程，同时限制肿瘤的发生。然而，衰老细胞的病理性堆积与一系列疾病和跨器官系统的年龄相关疾病有关。衰老细胞产生不同的旁分泌和内分泌信号，导致局部组织功能障碍，并产生有害的全身影响。在老年性衰退和慢性病的临床前和临床模型中，通过诱导凋亡的“衰老”药物或抑制衰老相关分泌表型的治疗方法SASP抑制剂去除衰老细胞，表明衰老细胞是缓解基本衰老过程影响的药理学靶点。然而，衰老细胞群在形式、功能、组织分布上是不同的，甚至在不同物种之间也不同，这可能解释了当前临床试验中从床到床的转换问题。在这里，我们回顾了衰老细胞的特征和针对它们的策略，包括免疫学方法，以及关键的细胞内信号通路。此外，我们还对目前人体试验中的感光疗法进行了综述。总体而言，需要研究开发有针对性的老年疗法，以满足老龄化和慢性病患者的需求。
Cellular senescence represents a distinct cell fate characterized by replicative arrest in response to a host of extrinsic and intrinsic stresses. Senescence provides programming during development and wound healing, while limiting tumorigenesis. However, pathologic accumulation of senescent cells is implicated in a range of diseases and age-associated morbidities across organ systems. Senescent cells produce distinct paracrine and endocrine signals, causing local tissue dysfunction and exerting deleterious systemic effects. Senescent cell removal by apoptosis-inducing “senolytic” agents or therapies that inhibit the senescence-associated secretory phenotype, SASP inhibitors, have demonstrated benefit in both pre-clinical and clinical models of geriatric decline and chronic diseases, suggesting senescent cells represent a pharmacologic target for alleviating effects of fundamental aging processes. However, senescent cell populations are heterogeneous in form, function, tissue distribution, and even differ among species, possibly explaining issues of bench-to-bedside translation in current clinical trials. Here, we review features of senescent cells and strategies for targeting them, including immunologic approaches, as well as key intracellular signaling pathways. Additionally, we survey current senolytic therapies in human trials. Collectively, there is demand for research to develop targeted senotherapeutics that address the needs of the aging and chronically-ill.
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影响因子：
2.6
作者：
通讯作者：
--
影响因子：
64.5
作者：
Burd CE;Sorrentino JA;Clark KS;Darr DB;Krishnamurthy J;Deal AM;Bardeesy N;Castrillon DH;Beach DH;Sharpless NE
通讯作者：
Sharpless NE
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：
14.9
作者：
Casella, Gabriel;Munk, Rachel;Gorospe, Myriam
通讯作者：
Gorospe, Myriam
影响因子：
3.9
作者：
Cherif, Hosni;Bisson, Daniel G.;Haglund, Lisbet
通讯作者：
Haglund, Lisbet