Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state

  1. Jean-Marc Lemaitre1,6
  1. 1Laboratory of Plasticity of the Genome and Aging, Institute of Functional Genomics, 34094 Montpellier Cedex 05, France;
  2. 2Laboratory of Neurological Disorders and Stem Cells, Institute of Human Genetics, 34396 Montpellier Cedex 05, France;
  3. 3Laboratory of Chromosomal Genetics, Medical Genetics Department, Hôpital CHRU Arnaud de Villeneuve, 34295 Montpellier Cedex 5, France;
  4. 4Laboratory of Early Embryo Development and Human Pluripotent Stem Cells, Institute for Research in Biotherapy, CHU Saint-Eloi Hospital, 34295 Montpellier Cedex 05, France
    • 5 Present address: Laboratory of Plasticity of the Genome and Aging, Institute of Functional Genomics, 141 Rue de la Cardonille, 34094 Montpellier Cedex 05, France.

    Abstract

    Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible. Thus, we show that our iPSCs generated from senescent and centenarian cells have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESCs. Finally, we show that senescent and centenarian-derived pluripotent stem cells are able to redifferentiate into fully rejuvenated cells. These results provide new insights into iPSC technology and pave the way for regenerative medicine for aged patients.

    Keywords

    Footnotes

    • Received July 7, 2011.
    • Accepted September 21, 2011.
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