1:Universidad de Sevilla

The revolutionary concept of nuclear cell reprogramming has redefined regenerative medicine in the 21st century. This new technology has emerged as a method of reversing the age and identity of virtually any cell to that of an embryonic-like stage. Under the action of the four reprogramming factors Oct4, Sox2, Klf4 and cMyc, known as the Yamanaka Factors, cells undergo significant changes on the epigenome and chromatin architecture. This genomic reorganization leads to a gradual shut-down of the somatic program and the reactivation of pluripotency genes. During the reprogramming process, multiple hallmarks associated with aging appear to “reverse” such as telomere size, epigenetic marks, DNA damage, levels of oxidative stress, mitochondrial dysfunction, and gene expression profiles. This rejuvenation has been confirmed in a variety of cells and tissues, including those of human origin. Importantly, the transient expression of the Yamanaka Factors, known as partial reprogramming, performs a first phase of epigenetic erasure without reaching pluripotency, which has been shown to be sufficient to promote rejuvenation and the appearance of intermediate progenitors. In vivo partial reprogramming has beneficial effects on organismal aging, including lifespan extension and tissue regeneration capacity. Furthermore, in vivo direct reprogramming from one cell type to another can be achieved through the action of lineage-specific transcription factors. We will discuss how cell reprogramming offers interesting possibilities to be explored for regenerative and healthy aging purposes.