Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice.
Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice.
复制标题
用衰老清除药物达沙替尼和槲皮素长期治疗可改善小鼠年龄依赖性椎间盘退变。
DOI：
10.1038/s41467-021-25453-2
复制
发表时间：
2021-09-03
影响因子：
16.6
通讯作者：
Risbud MV
中科院分区：
文献类型：
--
作者：
Novais EJ;Tran VA;Johnston SN;Darris KR;Roupas AJ;Sessions GA;Shapiro IM;Diekman BO;Risbud MV
Intervertebral disc degeneration is highly prevalent within the elderly population and is a leading cause of chronic back pain and disability. Due to the link between disc degeneration and senescence, we explored the ability of the Dasatinib and Quercetin drug combination (D + Q) to prevent an age-dependent progression of disc degeneration in mice. We treated C57BL/6 mice beginning at 6, 14, and 18 months of age, and analyzed them at 23 months of age. Interestingly, 6- and 14-month D + Q cohorts show lower incidences of degeneration, and the treatment results in a significant decrease in senescence markers p16INK4a, p19ARF, and SASP molecules IL-6 and MMP13. Treatment also preserves cell viability, phenotype, and matrix content. Although transcriptomic analysis shows disc compartment-specific effects of the treatment, cell death and cytokine response pathways are commonly modulated across tissue types. Results suggest that senolytics may provide an attractive strategy to mitigating age-dependent disc degeneration. Intervertebral disc degeneration is a leading cause of chronic back pain and disability. Here the authors show that long term treatment with senolytic compounds Dasatinib and Quercetin reduces disc senescence burden and ameliorates age-dependent degeneration in mice.
登录
查看更多内容
影响因子：
82.9
作者：
Farr JN;Xu M;Weivoda MM;Monroe DG;Fraser DG;Onken JL;Negley BA;Sfeir JG;Ogrodnik MB;Hachfeld CM;LeBrasseur NK;Drake MT;Pignolo RJ;Pirtskhalava T;Tchkonia T;Oursler MJ;Kirkland JL;Khosla S
通讯作者：
Khosla S
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
15.9
作者：
Guignabert, Christophe;Phan, Carole;Humbert, Marc
通讯作者：
Humbert, Marc
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.
影响因子：
3.9
作者：
Cherif, Hosni;Bisson, Daniel G.;Haglund, Lisbet
通讯作者：
Haglund, Lisbet