• Nelly Olova, Daniel J Simpson, Riccardo E Marioni, and Tamir Chandra.
• MRC Human Genetics Unit, MRC, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
• Aging Cell. 2019 Feb 1; 18 (1): e12877.

AbstractInduced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age-related decline. However, attempts to realize in vivo iPSC have invariably resulted in the formation of teratomas. Partial reprogramming in prematurely aged mice has shown promising results in alleviating age-related symptoms without teratoma formation. Does partial reprogramming lead to rejuvenation (i.e., "younger" cells), rather than dedifferentiation, which bears the risk of cancer? Here, we analyse the dynamics of cellular age during human iPSC reprogramming and find that partial reprogramming leads to a reduction in the epigenetic age of cells. We also find that the loss of somatic gene expression and epigenetic age follows different kinetics, suggesting that they can be uncoupled and there could be a safe window where rejuvenation can be achieved with a minimized risk of cancer.© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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