The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice
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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, p16 Ink4a , and p19 Arf 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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Removal of senescent cells by ABT-737 in the liver enhanced liver regeneration in adult mice without cancer.
“Removal of senescent cells by ABT-737 in the liver also enhanced liver regeneration in adult mice without cancer 211 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [211]
The Results and Discussion section, “ABT-737 treatment improves liver regeneration” (page unavailable), reports increased regenerative capacity after ABT-737 pretreatment in 6–8-month-old mice. But “ABT-737 decreases p21 and SASP expression” (page unavailable) reports no detectable increase in apoptosis in treated livers and suggests the drug may instead interfere with p21 and SASP expression. The improvement is supported; attributing it to removal of senescent cells is not established. (LLM, conf=0.88)
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Inhibition of Polyamine Catabolism Reduces Cellular Senescence
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Cellular Senescence in Acute Liver Injury: What Happens to the Young Liver?
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- Authors
- Ritschka, B., Knauer-Meyer, T., Gonçalves, D. S., Mas, A., Plassat, J.-L., Durik, M., Jacobs, H., Pedone, E., Di Vicino, U., Cosma, M. P., & Keyes, W. M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Barcelona Institute of Science and Technology (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2020-03-05
- Volume
- 34
- Issue
- 7-8
- Pages
- 489-494
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC7111259
- OpenAlex
- W3009846583
- Cited by
- 105
- References
- 34
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 18 · 2023: 20 · 2022: 14 · 2021: 17 · 2020: 9
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genes & Development (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- HAL (submittedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by-nc)
- Funders
- Spanish Ministry for Economy and Competitiveness (SAF2013-49082-P)
- La Fondation Recherche Medicale (AJE20160635985)
- Fondation ARC (PJA20181208104)
- IDEX Attractivité-University of Strasbourg (IDEX2017)
- La Fondation Schlumberger pour l'Education et la Recherche (FSER 19-Year 2018)
- ANR (ANR-19-CE13-0023-03, ANR-10-LABX-0030-INRT)
- Agence Nationale de la Recherche (ANR-10-IDEX-0002-02)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, ABT-737, p21, liver regeneration, partial hepatectomy, p16INK4a, p19ARF, senescence-associated gene expression
- MeSH terms
- Animals, Biphenyl Compounds, Cells, Cultured, Female, Gene Expression Regulation, Liver, Male, Mice, Inbred C57BL, Nitrophenols, Piperazines, Regeneration, Sulfonamides, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Models, Animal, Cyclin-Dependent Kinase Inhibitor p21, Mice
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