Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.
Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.
复制标题
DOI：
10.1111/jgs.17416
复制
发表时间：
2021-11
影响因子：
6.3
通讯作者：
Kirkland JL
中科院分区：
文献类型：
--
作者：
Verdoorn BP;Evans TK;Hanson GJ;Zhu Y;Langhi Prata LGP;Pignolo RJ;Atkinson EJ;Wissler-Gerdes EO;Kuchel GA;Mannick JB;Kritchevsky SB;Khosla S;Rizza SA;Walston JD;Musi N;Lipsitz LA;Kiel DP;Yung R;LeBrasseur NK;Singh RJ;McCarthy T;Puskarich MA;Niedernhofer LJ;Robbins PD;Sorenson M;Tchkonia T;Kirkland JL
在老年人和慢性病患者中，衰老细胞(SNC)的负担增加，SNC不分裂，但在新陈代谢中活跃，并通过细胞凋亡抵抗死亡。这些人也是感染SARS-CoV-2的发病率和死亡率最高的人群。SARS-CoV-2的并发症包括细胞因子风暴和多器官衰竭，这些因素通常是由SNCs通过其衰老相关分泌表型(SASP)所产生的。SASP可被感染相关病原体相关分子谱因子扩增。感觉剂，如非瑟素，选择性地消除SNCs，并延迟、预防或缓解老年实验动物和人类慢性疾病动物模型的多种疾病，包括肥胖、糖尿病和呼吸系统疾病。感觉剂目前正在进行临床试验，用于治疗与SNC有关的多种疾病，包括虚弱、肥胖/糖尿病、骨质疏松症以及心血管、肾脏和肺部疾病，这些疾病也是SARS-CoV-2发病率和死亡率的风险因素。一项临床试验正在进行中，以测试感觉剂是否能降低住院老年人中SARS-CoV-2的进展和发病率。在这里，我们描述了一项由美国国立卫生研究院资助的、多中心、安慰剂对照的针对已经或成为SARS-CoV-2 RT-PCR阳性的老年熟练护理设施(SNF)居民的非赛汀临床试验，包括针对这类患者基本衰老机制的理由。我们考虑了在SARS-CoV-2时代在长期护理环境中进行试验的后勤挑战，包括限制进入、同意程序、获取生物标本和临床数据的方法、人员配备、研究产品管理问题以及针对这些挑战的潜在解决方案。我们建议建立一个从事介入性临床试验的全国SNF网络。
The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS‐CoV‐2 infection. SARS‐CoV‐2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence‐associated secretory phenotype (SASP). The SASP can be amplified by infection‐related pathogen‐associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS‐CoV‐2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS‐CoV‐2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health‐funded, multicenter, placebo‐controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS‐CoV‐2 rtPCR‐positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long‐term care settings in the SARS‐CoV‐2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.
登录
查看更多内容
影响因子：
39.2
作者：
Fisher, Kimberly A.;Bloomstone, Sarah J.;Mazor, Kathleen M.
通讯作者：
Mazor, Kathleen M.
DOI：
10.1111/j.1532-5415.2010.03032.x
发表时间：
2010-09-01
影响因子：
6.3
作者：
Cherubini, Antonio;Del Signore, Susanna;Michel, Jean-Pierre
通讯作者：
Michel, Jean-Pierre
影响因子：
13.8
作者：
Fisman, David N.;Bogoch, Isaac;Tuite, Ashleigh R.
通讯作者：
Tuite, Ashleigh R.
影响因子：
2.5
作者：
Kennedy-Martin T;Curtis S;Faries D;Robinson S;Johnston J
通讯作者：
Johnston J
影响因子：
17.1
作者：
Mannick, Joan B.;Del Giudice, Giuseppe;Klickstein, Lloyd B.
通讯作者：
Klickstein, Lloyd B.