Summary: Main takeaway – continuing partial cellular reprogramming a bit further than most previous attempts seems to result in more substantial rejuvenation.
Usually, scientists stop partial reprogramming in the initiation phase, when cells still have not lost their cell identity, and have not yet started expressing any pluripotency genes. In this study, the authors went one step further (into the maturation phase) before stopping expression of the reprogramming factors. This resulted in temporary loss of some features of fibroblast cell identity, but cells reacquired their identity within a few weeks. What was the upside, you might ask? Well, the fibroblasts were rejuvenated by approximately 30 years at the epigenetic and transcriptomic level, and had some measurable improvements in collagen production and movement speed. The data collected also suggested that cells “remembered” their cell type during the maturation phase via epigenetic marks at gene enhancers (rather than promoters), and via persistent expression of some fibroblast genes.
Caveat: While the results sound very impressive (30 years of rejuvenation is nothing to be laughed at), they should be taken with a pinch of salt. For example, the sample sizes for the experiments backing up some of the claims (e.g., the epigenetic rejuvenation) are quite small, which makes making strong statements about how strong the rejuvenation was difficult. Despite this, the rejuvenation is still likely to have been quite substantial, and this method of partial cellular reprogramming is definitely worth exploring further
Original Article: https://elifesciences.org/articles/71624