is the only metazoan able to rejuvenate repeatedly after its medusae reproduce, hinting at biological immortality and challenging our understanding of aging. We present and compare whole-genome assemblies of and the nonimmortal using automatic and manual annotations, together with the transcriptome of life cycle reversal (LCR) process of We have identified variants and expansions of genes associated with replication, DNA repair, telomere maintenance, redox environment, stem cell population, and intercellular communication. Moreover, we have found silencing of polycomb repressive complex 2 targets and activation of pluripotency targets during LCR, which points to these transcription factors as pluripotency inducers in . Accordingly, we propose these factors as key elements in the ability of to undergo rejuvenation.