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

Genes & Development
Birgit RitschkaWilliam M Keyes

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.

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Citations

Apr 3, 2020·Genes & Development·Jodie Birch, Jesus Gil
Jun 25, 2020·Hepatology International·Matias J CaldezPhilipp Kaldis
Oct 21, 2020·Cellular and Molecular Life Sciences : CMLS·Severin MühlederRui Benedito
Jan 27, 2021·Cells·Dilara DemirciSerif Senturk
Dec 31, 2020·Neuropathology and Applied Neurobiology·Gabriela CarrenoJuan Pedro Martinez-Barbera
Mar 26, 2021·Seminars in Liver Disease·Sofia Ferreira-GonzalezStuart J Forbes
Mar 26, 2021·Seminars in Liver Disease·Raquel Maeso-Díaz, Jordi Gracia-Sancho
Apr 4, 2021·International Journal of Molecular Sciences·Abhishek Chandra, Jyotika Rajawat
Jun 12, 2021·JHEP Reports : Innovation in Hepatology·Abraham Stijn MeijnikmanAlbert Kornelis Groen
Jun 29, 2021·Mechanisms of Ageing and Development·Lucía Antelo-IglesiasManuel Collado
Jul 19, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Ulises Ahumada-CastroJ Cesar Cardenas
Nov 3, 2021·Cell Death & Disease·Jiayin DengLaura Senovilla
Nov 11, 2021·ELife·Diogo Paramos-de-CarvalhoLeonor Saúde

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