Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice.
Dasatinib plus quercetin attenuates some frailty characteristics in SAMP10 mice.
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DOI：
10.1038/s41598-022-06448-5
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发表时间：
2022-02-14
影响因子：
4.6
通讯作者：
Kodama A
中科院分区：
文献类型：
--
作者：
Ota H;Kodama A
Senolytics是一类选择性去除衰老细胞的药物。已经发现了达沙替尼和槲皮素，并且它们的组合已经显示出各种抗衰老效果。SAMP 10小鼠品系是大脑老化的模型。在这里，我们研究了组合对SAMP 10中脆弱特征的影响。以SAMP 10和SAMR 1小鼠作为正常衰老对照，研究了SAMP 10和SAMR 1小鼠的一些虚弱特征。在18-38周龄时用临床虚弱指数评估虚弱。采用行为学实验评价这些小鼠的运动和认知功能。将SAMP 10小鼠分为赋形剂组和联合组，研究这些功能和脑海马的组织学变化。最后，研究了组合对氧化应激诱导的衰老肌肉和神经元细胞的体外作用。结果发现，SAMP 10的脆弱指数高于SAMR 1。运动和认知功能SAMP 10比SAMR 1差。此外，在SAMP 10中，与载体相比，联合治疗改善了虚弱、运动和认知功能以及海马的衰老表型。总之，SAMP 10显示出比SAMR 1更明显的脆弱特征，达沙替尼和槲皮素在SAMP 10中减弱了它们。从我们的研究结果来看，衰老清除疗法可能有助于对虚弱的保护作用。
Senolytics are a class of drugs that selectively remove senescent cells. Dasatinib and quercetin have been discovered, and their combination has shown various anti-ageing effects. The SAMP10 mouse strain is a model of brain ageing. Here, we investigated the effect of combination on frailty characteristics in SAMP10. By comparing SAMP10 with SAMR1 mice as normal ageing controls, we investigated some frailty characteristics. Frailty was assessed at 18–38 weeks of age with a clinical frailty index. Motor and cognitive function of these mice were evaluated using behavioral experiments. SAMP10 mice were divided into vehicle and combination, and these functions and histological changes in the brain hippocampus were investigated. Finally, the in vitro effects of combination on oxidative stress-induced senescent muscle and neuronal cells were investigated. As a result, we found that frailty index was higher in SAMP10 than SAMR1. Motor and cognitive function were worse in SAMP10 than SAMR1. Furthermore, combination therapy improved frailty, motor and cognitive function, and the senescent phenotype of the hippocampus compared with vehicle in SAMP10. In summary, SAMP10 showed more marked frailty characteristics than SAMR1, and dasatinib and quercetin attenuated them in SAMP10. From our results, senolytic therapy might contribute protective effects against frailty.
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影响因子：
7.8
作者：
Zhu Y;Tchkonia T;Pirtskhalava T;Gower AC;Ding H;Giorgadze N;Palmer AK;Ikeno Y;Hubbard GB;Lenburg M;O'Hara SP;LaRusso NF;Miller JD;Roos CM;Verzosa GC;LeBrasseur NK;Wren JD;Farr JN;Khosla S;Stout MB;McGowan SJ;Fuhrmann-Stroissnigg H;Gurkar AU;Zhao J;Colangelo D;Dorronsoro A;Ling YY;Barghouthy AS;Navarro DC;Sano T;Robbins PD;Niedernhofer LJ;Kirkland JL
通讯作者：
Kirkland JL
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：
1.7
作者：
Jeong, SJ;Kim, K;Suh, YH
通讯作者：
Suh, YH
影响因子：
3.5
作者：
LUKACS, H;HIATT, ES;RAO, CV
通讯作者：
RAO, CV
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J