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3 thoughts on “Cellular Senescence in Regeneration”

  1. I don’t understand why the appearance of senescent cells in regenerating limb suggests that they positively contribute to the regeneration process.
    Doesn’t the fact that clearance of senescent cells improve regeneration support the opposite conclusion?

  2. Dear Manuel, thank you for your comment. The reason for stressing this possibility is that the timing and distribution of senescent cells in the regenerate suggest that these cells could be actively induced during the process (rather than being just a result of the initial tissue injury), and the fact that these senescent cells secrete a variety of compounds as part of their senescent phenotype (such as growth factors, MMPs, TIMPS and chemokines) that affect their microenvironment and could promote tissue remodelling. Indeed, transient positive functions for senescent cells have been reported during mouse development. However, these cells need to be eventually cleared, as their persistence leads to tissue disruption and malfunction – for example, their secretory phenotype can lead to permanent inflammation and ‘constant’ tissue remodelling. Basically, the evidence that is gradually accumulating suggests that senescent cells can act as a double-edged sword: they can have positive functions, when transient, but lead to negative effects in tissues, when permanent. This is why, in light of our observations during regeneration of complex structures, I suggest that the senescent cells that appear during regeneration of complex structures could play a positive role, but then they need to be eliminated by this highly efficient mechanism of immunesurveillance so they do not exert any negative effects in the new structure or future regeneration rounds. Yet, whether they contribute to the process is still in the realm of the hypothetical – I hope I will be able to tell you more on this soon, as it is an issue that I am currently addressing.

    1. Hi,
      Regarding the regeneration (took place in your experiment) it would not be really part or due to the previous senescence stage. Senescence and senescent cells are not able to induce regeneration of the skin fibroblasts in the aged person who will be keeping the wrinkles until death.

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