title: Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state.
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.
authors: Laboratory of Plasticity of the Genome and Aging, Institute of Functional Genomics, Montpellier Cedex, France.
authors: Laure
authors: L
authors: Lapasset
authors: Ollivier
authors: O
authors: Milhavet
authors: Alexandre
authors: A
authors: Prieur
authors: Emilie
authors: E
authors: Besnard
authors: Amelie
authors: A
authors: Babled
authors: Nafissa
authors: N
authors: Aït-Hamou
authors: Julia
authors: J
authors: Leschik
authors: Franck
authors: F
authors: Pellestor
authors: Jean-Marie
authors: JM
authors: Ramirez
authors: John
authors: J
authors: De Vos
authors: Sylvain
authors: S
authors: Lehmann
authors: Jean-Marc
authors: JM
authors: Lemaitre
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008928:Mitochondria / Q000378:metabolism; D012060:Rejuvenation; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology
chemical_list: D014157:Transcription Factors