Longevity-Promoting Compounds Enhance Pluripotent Stem Cell Generation

An interesting discovery: "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 (non-insertional) 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 mTOR (mammalian target of rapamycin) 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 AMPK (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 on the basis of the regulation of cellular reprogramming."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21615676


Make me curious -- Is pluripotency lost more quickly in cells of species with short life spans? If so, is the propensity of stem cells toward differentiation correlated with species' longevity?

Posted by: Lou Pagnuco at June 3rd, 2011 9:53 AM

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