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标题：Gerosuppression in confluent cells
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作者：Olga V. Leontieva ; Mikhail V. Blagosklonny
期刊名称：Aging
出版年度：2014
卷号：6
期号：12
页码：1010-1018
出版社：U.S.Department of Health & Human Service
摘要：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.
关键词：MTOR; rapalogs; sirolimus; aging; cancer; senescence