细胞生物学
细胞凋亡
下调和上调
表皮(动物学)
毛囊
生物
DNA损伤
衰老
干细胞
转基因
Bcl xL型
程序性细胞死亡
化学
DNA
生物化学
基因
解剖
作者
Reut Yosef,Noam Pilpel,Ronit Tokarsky-Amiel,Anat Biran,Yossi Ovadya,Seymour S. Cohen,Ezra Vadai,Liat Dassa,Elisheva Shahar,Reba Condiotti,Ittai Ben-Porath,Valery Krizhanovsky
摘要
Senescent cells, formed in response to physiological and oncogenic stresses, facilitate protection from tumourigenesis and aid in tissue repair. However, accumulation of such cells in tissues contributes to age-related pathologies. Resistance of senescent cells to apoptotic stimuli may contribute to their accumulation, yet the molecular mechanisms allowing their prolonged viability are poorly characterized. Here we show that senescent cells upregulate the anti-apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent cells induced by DNA damage in the lungs as well as senescent cells formed in the epidermis by activation of p53 through transgenic p14(ARF). Elimination of senescent cells from the epidermis leads to an increase in hair-follicle stem cell proliferation. The finding that senescent cells can be eliminated pharmacologically paves the way to new strategies for the treatment of age-related pathologies.
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