title: Gerosuppression in confluent cells.
abstract: The most physiological type of cell cycle arrest - namely, contact inhibition in dense culture - is the least densely studied. Despite cell cycle arrest, confluent cells do not become senescent. We recently described that mTOR (target of rapamycin) is inactive in contact-inhibited cells. Therefore, conversion from reversible arrest to senescence (geroconversion) is suppressed. I this Perspective, we further extended the gerosuppression model. While causing senescence in regular cell density, etoposide failed to cause senescence in contact-inhibited cells. A transient reactivation of mTOR favored geroconversion in etoposide-treated confluent cells. Like p21, p16 did not cause senescence in high cell density. We discuss that suppression of geroconversion in confluent and contact-inhibited cultures mimics gerosuppression in the organism. We confirmed that levels of p-S6 were low in murine tissues in the organism compared with mouse embryonic fibroblasts in cell culture, whereas p-Akt was reciprocally high in the organism.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elms and Carlson Streets, Buffalo, NY 14263, USA.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Leontieva
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Elms and Carlson Streets, Buffalo, NY 14263, USA.
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Blagosklonny
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000187:drug effects; D003260:Contact Inhibition / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005047:Etoposide; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases