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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Lapasset L,Milhavet O,Prieur A,Besnard E,Babled A,Aït-Hamou N,Leschik J,Pellestor F,Ramirez JM,De Vos J,Lehmann S,Lemaitre JM

doi

10.1101/gad.173922.111

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

2248-53

issue

21

eissn

0890-9369

issn

1549-5477

pii

25/21/2248

journal_volume

25

pub_type

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