TY - JOUR

T1 - Rapamycin induces pluripotent genes associated with avoidance of replicative senescence

AU - Pospelova, T.V.

AU - Bykova, T.V.

AU - Zubova, D.G.

AU - Katolikova, N.V.

AU - Yartzeva, N.M.

AU - Pospelov, V.A.

PY - 2013

Y1 - 2013

N2 - Primary rodent cells undergo replicative senescence, independent from telomere shortening. We have recently shown that treatment with rapamycin during passages 3-7 suppressed replicative senescence in rat embryonic fibroblasts (REFs), which otherwise occurred by 10-14 passages. Here, we further investigated rapamycin-primed cells for an extended number of passages. Rapamycin-primed cells continued to proliferate without accumulation of senescent markers. Importantly, these cells retained the ability to undergo serum starvation- and etoposide-induced cell cycle arrest. The p53/p21 pathway was functional. This indicates that rapamycin did not cause either transformation or loss of cell cycle checkpoints. We found that rapamycin activated transcription of pluripotent genes, oct-4, sox-2, nanog, as well as further upregulated telomerase (tert) gene. The rapamycin-derived cells have mostly non-rearranged, near-normal karyotype, Still, when cultivated for a higher number of passages, these cells acquired a chromoso

AB - Primary rodent cells undergo replicative senescence, independent from telomere shortening. We have recently shown that treatment with rapamycin during passages 3-7 suppressed replicative senescence in rat embryonic fibroblasts (REFs), which otherwise occurred by 10-14 passages. Here, we further investigated rapamycin-primed cells for an extended number of passages. Rapamycin-primed cells continued to proliferate without accumulation of senescent markers. Importantly, these cells retained the ability to undergo serum starvation- and etoposide-induced cell cycle arrest. The p53/p21 pathway was functional. This indicates that rapamycin did not cause either transformation or loss of cell cycle checkpoints. We found that rapamycin activated transcription of pluripotent genes, oct-4, sox-2, nanog, as well as further upregulated telomerase (tert) gene. The rapamycin-derived cells have mostly non-rearranged, near-normal karyotype, Still, when cultivated for a higher number of passages, these cells acquired a chromoso

KW - aging

KW - senescence

KW - mTOR

KW - gerosuppression

KW - rapalogs

U2 - 10.4161/cc.27396

DO - 10.4161/cc.27396

M3 - Article

VL - 12

SP - 3841

EP - 3851

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 24

ER -