Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types.
Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types.
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DOI：
10.1016/j.isci.2022.103848
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发表时间：
2022-02-18
期刊：
影响因子：
5.8
通讯作者：
Melov S
中科院分区：
文献类型：
--
作者：
Limbad C;Doi R;McGirr J;Ciotlos S;Perez K;Clayton ZS;Daya R;Seals DR;Campisi J;Melov S
细胞衰老是许多与年龄相关的病理的驱动因素。人们正在积极寻找一种名为老年降解剂的药物，这种药物可以通过靶向促进衰老细胞存活的基因来减轻或消除体内的衰老细胞。我们利用单细胞RNA测序确定了CryAB是一个强大的衰老诱导基因和潜在的衰老降解靶点。通过对CryAB的化学抑制物筛选，我们鉴定出胆固醇生物合成的内源性代谢物25-羟基胆固醇(25HC)是一种有效的感受性物质。然后，我们在培养的小鼠和人类细胞中以及在小鼠骨骼肌的体内验证了25HC是一种感觉剂。因此，25HC代表了一类潜在的衰老物质，它可能在对抗细胞衰老是关键驱动因素的疾病或生理方面有用。单细胞测序可用于促进发现感受性分解靶标CryAB是多种人和小鼠细胞类型的感觉性靶标25-羟基胆固醇是一种天然产生的感受性25-羟基胆固醇感受性在小鼠身上使用生物标记物15-dPGJ2生物科学；分子生物学；细胞生物学；转录组学进行验证
Cellular senescence is a driver of many age-related pathologies. There is an active search for pharmaceuticals termed senolytics that can mitigate or remove senescent cells in vivo by targeting genes that promote the survival of senescent cells. We utilized single-cell RNA sequencing to identify CRYAB as a robust senescence-induced gene and potential target for senolysis. Using chemical inhibitor screening for CRYAB disruption, we identified 25-hydroxycholesterol (25HC), an endogenous metabolite of cholesterol biosynthesis, as a potent senolytic. We then validated 25HC as a senolytic in mouse and human cells in culture and in vivo in mouse skeletal muscle. Thus, 25HC represents a potential class of senolytics, which may be useful in combating diseases or physiologies in which cellular senescence is a key driver. Single cell sequencing can be used to facilitate discovery of senolytic targets CRYAB is a senolytic target in multiple human and mouse cell types 25-hydroxycholesterol is a naturally produced senolytic 25-hydroxycholesterol senolysis was validated in mice using the biomarker 15-dPGJ2 Biological sciences; Molecular biology; Cell biology; Transcriptomics
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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：
10.1073/pnas.1404271111
发表时间：
2014-07-22
影响因子：
11.1
作者：
Gold, Elizabeth S.;Diercks, Alan H.;Aderem, Alan
通讯作者：
Aderem, Alan
影响因子：
7.8
作者：
Gonzalez-Gualda, Estela;Paez-Ribes, Marta;Munoz-Espin, Daniel
通讯作者：
Munoz-Espin, Daniel
影响因子：
11.1
作者：
Hickson, LaTonya J.;Prata, Larissa G. P. Langhi;Kirkland, James L.
通讯作者：
Kirkland, James L.
基于咪唑的新化合物对血红素加氧酶-1（HO-1）抑制剂的新结构见解： 生化和体外抗癌活性评估。
DOI：
10.3390/molecules23051209
发表时间：
2018-05-18
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Greish KF;Salerno L;Al Zahrani R;Amata E;Modica MN;Romeo G;Marrazzo A;Prezzavento O;Sorrenti V;Rescifina A;Floresta G;Intagliata S;Pittalà V
通讯作者：
Pittalà V