Aging and reprogramming: A two-way street

Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Current opinion in cell biology (Impact Factor: 8.47). 11/2012; 24(6). DOI: 10.1016/
Source: PubMed


Aging is accompanied by the functional decline of cells, tissues, and organs, as well as a striking increase in a wide range of diseases. The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) opens new avenues for the aging field and has important applications for therapeutic treatments of age-related diseases. Here we review emerging studies on how aging and age-related pathways influence iPSC generation and property. We discuss the exciting possibility that reverting to a pluripotent stem cell stage erases several deficits associated with aging and offers new strategies for rejuvenation. Finally, we argue that reprogramming provides a unique opportunity to model aging and perhaps exceptional longevity.

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    • "By contrast, the modeling of late-onset disorders has often failed to faithfully recapitulate the late-stage features of the disease phenotypes, such as macromolecular protein aggregates ( plaques) or the progressive deterioration of neuronal structures resulting in cell death (Srikanth and Young-Pearse, 2014). The difficulties in modeling late-onset disease phenotypes may be related to the reset of donor age in human pluripotent stem cells (hPSCs) following reprogramming (Suhr et al., 2010; Lapasset et al., 2011; Mahmoudi and Brunet, 2012; Frobel et al., 2014). The resulting hPSCs give rise to cells that typically show the behavior of fetal stage cells following in vitro differentiation. "
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    • "Research article variety of different reprogramming factors, reprogramming enhancers, and cell types have been evaluated (Liao et al., 2008; Judson et al., 2009; Mali et al., 2010; Cheng et al., 2011; Niibe et al., 2011; Szablowska-Gadomska et al., 2011; Zhang et al., 2011; Li and Rana, 2012; Lin et al., 2012; Liu et al., 2012; Mahmoudi and Brunet, 2012; Okita et al., 2013; Zhang and Wu, 2013). Of the accessible cell types used for iPSC generation, the reprogramming of keratinocytes has been shown to be as much as 100-fold more efficient and at least twofold faster than the reprogramming of dermal fibroblasts (Aasen et al., 2008). "
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    • "It is now clear that reprogramming efficiency is sensitive to various factors, among them the genetic background of the source of cells, the tissue source, the reprogramming method, and the combination of the reprogramming factors. In addition, recent high impact studies suggested that aging is a direct barrier to the generation of iPSCs (Banito et al. 2009; Mahmoudi and Brunet 2012). "
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