Fig. 1

Cellular reprogramming experiments that induce epigenetic rejuvenation. A Fluorescent recovery of heterochromatin protein 1β (HP1β) in senescent cells was restored to the same level as non-senescent cells after nine days of OSKML treatment [119]. B OSKM treatment increased lifespan of progeria mice, improved the regenerative capacity of muscle and pancreas, as well as glucose tolerance [74]. C Overlaid summary of iPSC reprogramming time-course experiments by [118] and [73]. Upper panel: Horvath multi-tissue age predictor applied to OSKM-expressing adult fibroblasts [118]. The experimental setup of Gill et al. includes OSKM-free culturing at the time points in red for a minimum of four weeks. Day 13 was identified by Gill et al. as most suitable for OSKM withdrawal, where highest stable rejuvenation (eAge reduction) can be achieved: approximately 30 years, same as shown before OSKM withdrawal by Olova et al. Lower panel: The bars align with the time-course and summarise phases and patterns of gene expression as reported in Olova et al. “eAge drop onset” and “Point of no return” cannot be attributed to a precise day in the presented data as they occur between actual experimental time points. D OSKMNL-treatment of aged fibroblasts and endothelial cells results in a significant decrease in eAge (according to the Horvath clock), and a transcription profile resembling that of young fibroblasts/endothelial cells [125]. E 4 weeks of OSK treatment of 12 month old mice resulting in improved DNA methylation ageing signature, rejuvenation of age-related gene expression, and improved visual performance [127]