The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
The senotherapeutic drug ABT-737 disrupts aberrant p21 expression to restore liver regeneration in adult mice
Open accessPublished version of a preprint
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 also enhanced liver regeneration in adult mice without cancer 211 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [211]
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Cites
Naturally occurring p16Ink4a-positive cells shorten healthy lifespan
Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., A. Saltness, R., Jeganathan, K. B., Verzosa, G. C., Pezeshki, A., et al. (2016) · Nature · doi:10.1038/nature16932 · Cited by 2,876
Self-citationCellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818
Transient Regenerative Potential of the Neonatal Mouse Heart
Porrello, E. R., Mahmoud, A. I., Simpson, E., Hill, J. A., Richardson, J. A., Olson, E. N., & Sadek, H. A. (2011) · Science · doi:10.1126/science.1200708 · Cited by 2,545
Cellular senescence in aging and age-related disease: from mechanisms to therapy
Childs, B. G., Durik, M., Baker, D. J., & van Deursen, J. M. (2015) · Nature Medicine · doi:10.1038/nm.4000 · Cited by 2,363
Self-citationSenolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
Senescence of Activated Stellate Cells Limits Liver Fibrosis
Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., Yee, H., Zender, L., & Lowe, S. W. (2008) · Cell · doi:10.1016/j.cell.2008.09.015 · Cited by 2,027
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice
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Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline
Bussian, T. J., Aziz, A., Meyer, C. F., Swenson, B. L., van Deursen, J. M., & Baker, D. J. (2018) · Nature · doi:10.1038/s41586-018-0543-y · Cited by 1,289
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Integrating senotherapeutics into transplantation: liver reconditioning in an aging donor pool
Buch, M. L., Esser, H., Perera, H., Zheng, R., Ferreira-González, S., & Forbes, S. J. (2026) · Transplant International · doi:10.3389/ti.2026.16347
Therapeutic priming of liver regeneration: from mechanisms to ex vivo machine perfusion
Tropp, S. Y., Jaishankar, D., Atkinson, C., & Nadig, S. N. (2026) · Frontiers in Transplantation · doi:10.3389/frtra.2026.1841091 · Cited by 1
Senescence targeting re-enables injury-responsive repair in a human RPE aging modelPreprint
Ritschka, B., Etl, C., Perez, F. B., Ishihara, K., Almedawar, S., Leyva‐González, M. A., Neubauer, H., Bakker, R. A., & Tanaka, E. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.26.722664
Self-citationYu-Tong, C. H. E. N., & Zheng-Wei, X. I. E. (2026) · Shengming kexue · doi:10.3724/cbls.2026096
Cellular senescence: six decades of discovery and reinvention
Klaver, M., Steeneken, L. S., Veeningen, N., Altulea, A., & Demaria, M. (2026) · The EMBO Journal · doi:10.1038/s44318-026-00922-w
Metadata
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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