Abstract
Ageing, death, and potential immortality lie at the heart of biology, but two seemingly incompatible paradigms coexist in different research communities and have done since the nineteenth century. 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 ‘immortalized’ 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 ‘immortal’ cell lines, by excreting damaged cell constituents. In electronic supplementary material, appendix, I outline nine ways in which this hypothesis could be tested.
Highlights
Since the late nineteenth century, there have been two principal schools of thought about cellular ageing
The other paradigm assumes that some cells are potentially immortal and immune to senescence, namely unicellular organisms, the germ cells of multicellular organisms and ‘immortal’ cell lines grown in laboratories
The patterns of cell division in plants are consistent with the idea that damaged cell constituents (DCC) build up in all cells over time, but some cells can be rejuvenated by asymmetrical cell division (ACD) or by the dilution of DCC by multiple fission
Summary
Death, and potential immortality lie at the heart of biology, but two seemingly incompatible paradigms coexist in different research communities and have done since the nineteenth century. Recent research with animal cells, yeasts and bacteria show that damaged cell constituents do build up, but can be diluted by growth and cell division, especially by asymmetric cell division. Mammalian embryonic stem cells and many cancerous and ‘immortalized’ cell lines divide symmetrically, and yet replicate indefinitely. How do they acquire their potential immortality? 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 ‘immortal’ cell lines, by excreting damaged cell constituents. Appendix, I outline nine ways in which this hypothesis could be tested
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