Induced pluripotent stem cells, embryonic stem cells and cell passaging. (A
C) Induced pluripotent stem (iPS) cells have a lower DNAm age than corresponding primary cells in (A) data set 77 (Kruskal Wallis P-value 1E-14), (B) data set 78 (P = 8E-10), and (C) data set 79 (P = 0.0062). (A,B) There is no significant difference in DNAm age between ES cells and iPS cells (both restricted to cell passage numbers less than 15) in data sets 77 and 78, respectively. (D,E) DNAm age of human ES cell lines and adult tissues in data sets 80 and 81, respectively. (F-J) Cell passage number (y-axis) is significantly correlated with DNAm age (x-axis). (F) Cell passage number (y-axis) versus DNAm age in data set 77. Points are colored by cell type (black for ES cells, red for iPS cells, blue for somatic cells). (G,H) Analogous results for iPS cells (cor = 0.33, P = 0.025) and embryonic stem cells (cor = 0.28, P = 0.0023) from data set 77. (I,J) Validation of these findings in two independent data sets, 78 and 79, respectively. Panel (J) involves only stem cells. Panels (A-C) involve cells that had undergone fewer than 15 cell passages. Panels (C,J) are restricted to cells that were not irradiated. The bar plots show the mean value ±1 standard error.