作者
LaTonya J Hickson, Larissa GP Langhi Prata, Shane A Bobart, Tamara K Evans, Nino Giorgadze, Shahrukh K Hashmi, Sandra M Herrmann, Michael D Jensen, Qingyi Jia, Kyra L Jordan, Todd A Kellogg, Sundeep Khosla, Daniel M Koerber, Anthony B Lagnado, Donna K Lawson, Nathan K LeBrasseur, Lilach O Lerman, Kathleen M McDonald, Travis J McKenzie, João F Passos, Robert J Pignolo, Tamar Pirtskhalava, Ishran M Saadiq, Kalli K Schaefer, Stephen C Textor, Stella G Victorelli, Tammie L Volkman, Ailing Xue, Mark A Wentworth, Erin O Wissler Gerdes, Yi Zhu, Tamara Tchkonia, James L Kirkland
发表日期
2019/9/1
期刊
EBioMedicine
卷号
47
页码范围
446-456
出版商
Elsevier
简介
Background
Senescent cells, which can release factors that cause inflammation and dysfunction, the senescence-associated secretory phenotype (SASP), accumulate with ageing and at etiological sites in multiple chronic diseases. Senolytics, including the combination of Dasatinib and Quercetin (D + Q), selectively eliminate senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment. In the first clinical trial of senolytics, D + Q improved physical function in patients with idiopathic pulmonary fibrosis (IPF), a fatal senescence-associated disease, but to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans.
Methods
In an open label Phase 1 pilot study, we administered 3 days of oral D 100 mg and Q 1000 mg to subjects with diabetic kidney disease (N = 9; 68·7 ± 3·1 years old; 2 female; BMI:33 …
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