RT alterations in physiological and premature aging are not linked to cellular senescence. (a) Schematic depiction of the distinct cell samples analyzed: fibroblasts from distinct-age donors and from HGPS patients. (b) Correlation matrix of genome-wide RT programs from human ES cell lines (ESC_BG01, ESC_BG02, ESC_H1, ESC_H7, ESC_H9) and fibroblasts of distinct-age donors (Fibro IMR90, post-natal BJ, 74 yr, 92 yr and 96 yr) and HGPS patients (Prog_2yr, Prog_8yr_A and Prog_8yr_B). (c-f) RT profiles of a representative chromosome segment comparing normal IMR90 fibroblasts with HGPS cells (c); normal IMR90 fibroblasts with fibroblasts of distinct age donors (D); proliferative and pre-senescent cells from fetal fibroblasts (e); and proliferative and pre-senescent cells from fibroblasts of 74 yr old donor (f). (g) Overlap between the RT changes observed in HGPS, natural aging and cellular senescence. (h) Percentage of changes from early to late replication (EtoL) or late to early (LtoE) in HGPS and natural aging.