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The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice.


ABSTRACT: Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16Ink4a, and p19Arf become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a senescence-inhibiting drug improves regeneration, by disrupting aberrantly prolonged p21 expression. This work suggests that senescence may initially develop from heterogeneous cellular responses, and that senotherapeutic drugs might be useful in promoting organ regeneration.

SUBMITTER: Ritschka B 

PROVIDER: S-EPMC7111259 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice.

Ritschka Birgit B   Knauer-Meyer Tania T   Gonçalves Daniel Sampaio DS   Mas Alba A   Plassat Jean-Luc JL   Durik Matej M   Jacobs Hugues H   Pedone Elisa E   Di Vicino Umberto U   Cosma Maria Pia MP   Keyes William M WM  

Genes & development 20200305 7-8


Young mammals possess a limited regenerative capacity in some tissues, which is lost upon maturation. We investigated whether cellular senescence might play a role in such loss during liver regeneration. We found that following partial hepatectomy, the senescence-associated genes p21, p16<sup>Ink4a</sup>, and p19<sup>Arf</sup> become dynamically expressed in different cell types when regenerative capacity decreases, but without a full senescent response. However, we show that treatment with a se  ...[more]

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