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The universal senescence paradigm sees senescence as inevitable in all cells. Damage accumulates. The potential immortality paradigm sees some cells as potentially immortal, especially unicellular organisms, germ cells and cancerous cells. Recent research with animal cells, yeasts and bacteria show that damaged cell constituents do in fact build up, but can be diluted by growth and cell division, especially by asymmetric cell division. By contrast, mammalian embryonic stem cells and many cancerous and \u2018immortalized\u2019 cell lines divide symmetrically, and yet replicate indefinitely. How do they acquire their potential immortality? I suggest they are rejuvenated by excreting damaged cell constituents in extracellular vesicles. If so, our understanding of cellular senescence, rejuvenation and potential immortality could be brought together in a new synthesis, which I call the cellular rejuvenation hypothesis: damaged cell constituents build up in all cells, but cells can be rejuvenated either by growth and cell division or, in \u2018immortal\u2019 cell lines, by excreting damaged cell constituents. In electronic supplementary material, appendix, I outline nine ways in which this hypothesis could be tested.<\/jats:p>","DOI":"10.1098\/rspb.2021.2434","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T03:12:18Z","timestamp":1646190738000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Cellular senescence, rejuvenation and potential immortality"],"prefix":"10.1098","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-4014","authenticated-orcid":true,"given":"A. 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