PMID- 21615676
OWN - NLM
STAT- MEDLINE
DCOM- 20120109
LR  - 20211203
IS  - 1474-9726 (Electronic)
IS  - 1474-9718 (Linking)
VI  - 10
IP  - 5
DP  - 2011 Oct
TI  - Rapamycin and other longevity-promoting compounds enhance the generation of mouse 
      induced pluripotent stem cells.
PG  - 908-11
LID - 10.1111/j.1474-9726.2011.00722.x [doi]
AB  - Reprogramming of somatic cells to a pluripotent state was first accomplished 
      using retroviral vectors for transient expression of pluripotency-associated 
      transcription factors. This seminal work was followed by numerous studies 
      reporting alternative (noninsertional) reprogramming methods and various 
      conditions to improve the efficiency of reprogramming. These studies have 
      contributed little to an understanding of global mechanisms underlying 
      reprogramming efficiency. Here we report that inhibition of the mammalian target 
      of rapamycin (mTOR) pathway by rapamycin or PP242 enhances the efficiency of 
      reprogramming to induced pluripotent stem cells (iPSCs). Inhibition of the 
      insulin/IGF-1 signaling pathway, which like mTOR is involved in control of 
      longevity, also enhances reprogramming efficiency. In addition, the small 
      molecules used to inhibit these pathways also significantly improved longevity in 
      Drosophila melanogaster. We further tested the potential effects of six other 
      longevity-promoting compounds on iPSC induction, including two sirtuin activators 
      (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K 
      (phosphoinositide 3-kinase) inhibitor (LY294002), an antioxidant (curcumin), and 
      an activating adenosine monophosphate-activated protein kinase activator 
      (metformin). With the exception of metformin, all of these chemicals promoted 
      somatic cell reprogramming, though to different extents. Our results show that 
      the controllers of somatic cell reprogramming and organismal lifespan share some 
      common regulatory pathways, which suggests a new approach for studying aging and 
      longevity based on the regulation of cellular reprogramming.
CI  - (c) 2011 The Authors. Aging Cell (c) 2011 Blackwell Publishing Ltd/Anatomical Society 
      of Great Britain and Ireland.
FAU - Chen, Taotao
AU  - Chen T
AD  - Laboratory of Molecular Cell Biology and Center of Cell Signaling, Institute of 
      Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, 
      Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai, China.
FAU - Shen, Li
AU  - Shen L
FAU - Yu, Jie
AU  - Yu J
FAU - Wan, Hongjiang
AU  - Wan H
FAU - Guo, Ao
AU  - Guo A
FAU - Chen, Jiekai
AU  - Chen J
FAU - Long, Yuan
AU  - Long Y
FAU - Zhao, Jian
AU  - Zhao J
FAU - Pei, Gang
AU  - Pei G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110614
PL  - England
TA  - Aging Cell
JT  - Aging cell
JID - 101130839
RN  - 0 (Chromones)
RN  - 0 (Flavonoids)
RN  - 0 (Flavonols)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - OO2ABO9578 (fisetin)
RN  - U87FK77H25 (Spermidine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Cellular Reprogramming
MH  - Chromones/pharmacology
MH  - Flavonoids/pharmacology
MH  - Flavonols
MH  - Induced Pluripotent Stem Cells/*drug effects
MH  - *Longevity
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Signal Transduction
MH  - Sirolimus/*pharmacology
MH  - Spermidine/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2011/05/28 06:00
MHDA- 2012/01/10 06:00
CRDT- 2011/05/28 06:00
PHST- 2011/05/28 06:00 [entrez]
PHST- 2011/05/28 06:00 [pubmed]
PHST- 2012/01/10 06:00 [medline]
AID - 10.1111/j.1474-9726.2011.00722.x [doi]
PST - ppublish
SO  - Aging Cell. 2011 Oct;10(5):908-11. doi: 10.1111/j.1474-9726.2011.00722.x. Epub 
      2011 Jun 14.