The whole-genome assemblies of mortal and immortal cnidarians are presented in the Proceedings of the National Academy of Sciences this week, providing insights into how certain species of these aquatic invertebrates are able to rejuvenate to overcome the aging process. One cnidarian, the jellyfish Turritopsis dohrnii, is capable of repeated rejuvenation after sexual reproduction, hinting at biological immortality. To investigate this phenomenon, a team led by scientists from the Universidad de Oviedo sequenced and analyzed the genomes of T. dohrnii and Turritopsis rubra, a jellyfish that is incapable of rejuvenation, and compared their findings to other cnidarians. They uncover candidate genes and pathways related to genomic instability, telomere attrition, mitochondrial dysfunction, stem cell exhaustion, cellular senescence, and intercellular communication. The researchers also find that two of the main mechanisms for cell reprogramming — silencing of PRC2 targets and activation of pluripotency targets — are involved in T. dohrnii life cycle reversal, which suggests these transcription factors may mediate the activation of pluripotency signaling in the immortal jellyfish. "Altogether, this work provides insights into the molecular mechanisms giving T. dohrnii the remarkable capacity to rejuvenate and escape death," the study's authors write.