Targeting senescent cells in translational medicine

被引:210
作者
Paez-Ribes, Marta [1 ]
Gonzalez-Gualda, Estela [1 ]
Doherty, Gary J. [2 ]
Munoz-Espin, Daniel [1 ]
机构
[1] Univ Cambridge, Dept Oncol, CRUK Cambridge Ctr Early Detect Programme, Hutchison MRC Res Ctr, Cambridge, England
[2] Cambridge Univ Hosp NHS Fdn Trust, Dept Oncol, Cambridge Biomed Campus, Cambridge, England
基金
英国医学研究理事会;
关键词
age-related disorders; cellular senescence; SASP; senolytic drugs; senoprobes; ACTIVATED STELLATE CELLS; CELLULAR SENESCENCE; SECRETORY PHENOTYPE; BETA-GALACTOSIDASE; DNA-DAMAGE; FLUORESCENT-PROBE; BCL-2; FAMILY; CANCER; INHIBITORS; COMBINATION;
D O I
10.15252/emmm.201810234
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs during ageing, contribute to tissue dysfunction and give rise to pathological manifestations. Senescence is therefore a defining feature of a variety of human age-related disorders, including cancer, and targeted elimination of these cells has recently emerged as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration. In addition, in vivo identification of senescent cells has significant potential for early diagnosis of multiple pathologies. Here, we review existing senolytics, small molecules and drug delivery tools used in preclinical therapeutic strategies involving cellular senescence, as well as probes to trace senescent cells. We also review the clinical research landscape in senescence and discuss how identifying and targeting cellular senescence might positively affect pathological and ageing processes.
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页数:19
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