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Programmed Cells from Basic Neuroscience to Therapy pp 119–130Cite as

On the Search for Reliable Human Aging Models: Understanding Aging by Nuclear Reprogramming

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Part of the book series: Research and Perspectives in Neurosciences ((NEUROSCIENCE,volume 20))

Abstract

Reprogramming technologies, and particularly the generation of induced pluripotent stem cells (iPSCs), have demonstrated the possibility of personalized disease modeling in a dish. Importantly, the fact that pluripotent stem cells can give rise to all cell types of an organism, along with the technical progress allowing for their isolation, brings to mind fantasies like the fountain of youth and eternal regeneration and represents one of the most promising scientific fields with clinical implications. Furthermore, increasing evidence indicates that aging “defects” observed in patient somatic cells could be erased or alleviated by direct reprogramming towards pluripotency and rapidly recapitulated upon directed differentiation to specific cell lineages (Liu et al., Nature 472:221–225, 2011a). Thus, iPSC models of aging facilitate human aging studies by shortening the time required for physiological manifestation of aging-related defects from years, in the case of a human being, to days when stem cell models are applied. Moreover, the combination of gene-editing and iPSC models of aging will also allow for the generation of precisely targeted reporter cell lines of high value for studying normal differentiation processes and high throughput screens. However, a major concern regarding the use of iPSCs for disease modeling has to be taken into account prior to their broad application in drug discovery studies, which is that the use of patient-derived iPSCs bears another important experimental limitation, the lack of appropriate genetically matched control lines (Soldner et al., Cell 146:318–331, 2011; Liu et al., Cell Stem Cell 8:688–694, 2011b).

In this chapter we will discuss the most recent advancements in the use of pluripotent stem cells as models of disease with special emphasis on their use, alongside gene editing, for the study of human aging and its associated pathologies.

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Acknowledgments

Work in the laboratory of J.C.I.B. was supported by grants from MINECO, Fundacion Cellex, G. Harold and Leila Y. Mathers Charitable Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, The Ellison Medical Foundation and IPSEN Foundation.

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Authors and Affiliations

  1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Ignacio Sancho-Martinez, Emmanuel Nivet & Juan Carlos Izpisua Belmonte

  2. Center for Regenerative Medicine in Barcelona, Dr. Aiguader 88, Barcelona, 08003, Spain

    Juan Carlos Izpisua Belmonte

Authors
  1. Ignacio Sancho-Martinez
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  2. Emmanuel Nivet
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  3. Juan Carlos Izpisua Belmonte
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Correspondence to Juan Carlos Izpisua Belmonte .

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Editors and Affiliations

  1. , Laboratory of Genetics, The Salk Institute f. Biological Studies, North Torrey Pines Road 10010, La Jolla, 92037, California, USA

    Fred H. Gage

  2. Fondation Ipsen, Quai George Gorse 65, Boulogne Billancourt, 92650, France

    Yves Christen

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Sancho-Martinez, I., Nivet, E., Belmonte, J.C.I. (2013). On the Search for Reliable Human Aging Models: Understanding Aging by Nuclear Reprogramming. In: Gage, F., Christen, Y. (eds) Programmed Cells from Basic Neuroscience to Therapy. Research and Perspectives in Neurosciences, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36648-2_11

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