Fig. 3

Nuclear reprogramming depicted as a multi-layered process. Nuclear reprogramming can be separated into age and developmental reprogramming. Age reprogramming itself consists of several separate elements the most important of which are the nine hallmarks of ageing [9]. In bold are those hallmarks that have been age-reprogrammed experimentally. These include epigenetic rejuvenation [20, 26, 28], DNA damage [28], cellular senescence [28] and mitochondrial dysfunction [28]. It remains to be seen if the other hallmarks (grey) can be age-reprogrammed without developmental reprogramming. Developmental reprogramming is also depicted as being multi-layered, consisting of many different developmental pathways (1 to n) that have the potential of being reprogrammed independently. In essence, the multi-layered nature of nuclear reprogramming reflects the restriction in developmental and ageing potential that takes place during the transition from egg to adult to old age, where each restriction is reprogrammed to reacquire the potential it once had