Rapamycin decelerates cellular senescence.
When the cell cycle is arrested but cellular growth is not, then cells senesce, permanently losing proliferative potential. Here we demonstrated that the duration of cell cycle arrest determines a progressive loss of proliferative capacity. In human and rodent cell lines, rapamycin (an inhibitor of mTOR) dramatically decelerated loss of proliferative potential caused by ectopic p21, p16 and sodium butyrate-induced p21. Thus, when the cell cycle was arrested by these factors in the presence of rapamycin, cells retained the capacity to resume proliferation, once p21, p16 or sodium butyrate were removed. While rapamycin prevented the permanent loss of proliferative potential in arrested cells, it did not force the arrested cells into proliferation. During cell cycle arrest, rapamycin transformed the irreversible arrest into a reversible condition. Our data demonstrate that senescence can be pharmacologically suppressed.
Demidenko
Zoya N
ZN
Oncotarget, Albany, NY, USA.
Zubova
Svetlana G
SG
Bukreeva
Elena I
EI
Pospelov
Valery A
VA
Pospelova
Tatiana V
TV
Blagosklonny
Mikhail V
MV
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D002087:Butyrates; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009363:Neoplasm Proteins; D007544:Isopropyl Thiogalactoside; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus