Repair, regeneration and rejuvenation require un-entangling pluripotency from senescence.

There is a notion that pluripotency and senescence, represent two extremes of life of cells. Pluripotent cells display epigenetic youth, unlimited proliferative capacity and pluripotent differentiating potential whereas cells that reach the Hayflick limit, transit to senescence, undergo permanent inhibition of cell replication and create an aging tissue landscape. However, pluripotency and senescence appear to be intimately linked and are jointly generated in many different contexts such as during embryogenesis or formation of tissue spheroids, in stem cell niches, cancer, or by induction of a pluripotent state (induced pluripotency). Tissue damage and senescence provide signals that are critical to generation of a pluripotent state and, in turn, pluripotency, induces senescence. Thus, it follows, that precisely timed control of senescence is required for harnessing the full benefits of both senescence and its associated pluripotency during tissue regeneration or rejuvenation.