Aging vs. rejuvenation: reprogramming to iPSCs does not turn back the clock for somatic mitochondrial DNA mutations

The process of cellular reprogramming is believed to be able to “turn back the developmental clock” by allowing somatic cells to acquire a state that is normally associated only with embryonic stem cells (ESCs) (1). Indeed, human induced pluripotent stem cells (iPSCs) can be obtained from aged individuals and still show the key properties of ESCs, including self-renewal, elongated telomeres, and round-shaped mitochondria with underdeveloped cristae (2). However, it remained to be determined whether reprogramming to pluripotency could actually erase aging-associated signatures and thus represent a rejuvenation route. A new paper by Mitalipov and colleagues (3) now clearly demonstrates that iPSCs not only do not erase the signs of aging but, due to their clonal origin, may even reveal aging-related defects in the mitochondrial DNA (mtDNA) that were not detectable in the whole parental tissues.