Rejuvenating Senescent and Centenarian Human Cells by Reprogramming Through the Pluripotent State

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2011 Nov 8

PMID 22056670

Citations 266

Authors

Laure Lapasset

Ollivier Milhavet

Alexandre Prieur

Emilie Besnard

Amelie Babled

Nafissa Ait-Hamou

Julia Leschik

Franck Pellestor

Jean-Marie Ramirez

John De Vos

Sylvain Lehmann

Jean-Marc Lemaitre

Affiliations

Soon will be listed here.

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.

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