Partial reprogramming induces a steady decline in epigenetic age before loss of somatic identity

Induced pluripotent stem cells (IPSCs), with their unlimited regenerative capacity, carry the promise for tissue replacement to counter age-related decline. However, attempts to realise 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 cellular age during iPSC reprogramming and find that partial reprogramming leads to a reduction in the biological age of cells. We also find that the loss of somatic gene expression and epigenetic age follow different kinetics, suggesting that rejuvenation can be achieved with a minimised risk of cancer.