Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury

Nature Aging (2024)Cite this article

Subjects

Abstract

Excessive amounts of reactive oxygen species (ROS) lead to macromolecular damage and high levels of cell death with consequent pathological sequelae. We hypothesized that switching cell death to a tissue regenerative state could potentially improve the short-term and long-term detrimental effects of ROS-associated acute tissue injury, although the mechanisms regulating oxidative stress-induced cell fate decisions and their manipulation for improving repair are poorly understood. Here, we show that cells exposed to high oxidative stress enter a poly (ADP-ribose) polymerase 1 (PARP1)-mediated regulated cell death, and that blocking PARP1 activation promotes conversion of cell death into senescence (CODIS). We demonstrate that this conversion depends on reducing mitochondrial Ca2+ overload as a consequence of retaining the hexokinase II on mitochondria. In a mouse model of kidney ischemia–reperfusion damage, PARP inhibition reduces necrosis and increases transient senescence at the injury site, alongside improved recovery from damage. Together, these data provide evidence that converting cell death into transient senescence can therapeutically benefit tissue regeneration.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PARP1 signaling has a major role in the decision between senescence and death in response to oxidative stress.
Fig. 2: PARP activation regulates Ca2+ signaling induced by oxidative stress.
Fig. 3: Hexokinase is a downstream effector of PARP that modulates Ca2+ signaling.
Fig. 4: PARP inhibition reduces necrotic kidney injury, promotes senescence and limits long-term kidney pathology.

Similar content being viewed by others

Data availability

The RNA-seq dataset generated in this study is publicly accessible at the NCBI as BioProject no. PRJNA945397. The public dataset41 analyzed in this study has been deposited under accession no. GSE130727. All other data supporting the findings of this study are available as source data files or from the corresponding author upon reasonable request (m.demaria@umcg.nl).

References

  1. Sies, H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: oxidative eustress. Redox Biol. 11, 613–619 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sies, H. & Jones, D. P. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat. Rev. Mol. Cell Biol. 21, 363–383 (2020).

    Article  CAS  PubMed  Google Scholar 

  3. Abdulle, A. E. et al. Serum free thiols predict cardiovascular events and all-cause mortality in the general population: a prospective cohort study. BMC Med. 18, 130 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tang, D., Kang, R., Berghe, T. V., Vandenabeele, P. & Kroemer, G. The molecular machinery of regulated cell death. Cell Res. 29, 347–364 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Vanden Berghe, T., Linkermann, A., Jouan-Lanhouet, S., Walczak, H. & Vandenabeele, P. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat. Rev. Mol. Cell Biol. 15, 135–147 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Kers, J., Leemans, J. C. & Linkermann, A. An overview of pathways of regulated necrosis in acute kidney injury. Semin. Nephrol. 36, 139–152 (2016).

    Article  CAS  PubMed  Google Scholar 

  7. Granger, D. N. & Kvietys, P. R. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol. 6, 524–551 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gorlach, A., Bertram, K., Hudecova, S. & Krizanova, O. Calcium and ROS: a mutual interplay. Redox Biol. 6, 260–271 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Criddle, D. N. et al. Calcium signalling and pancreatic cell death: apoptosis or necrosis? Cell Death Differ. 14, 1285–1294 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Giorgi, C., Marchi, S. & Pinton, P. The machineries, regulation and cellular functions of mitochondrial calcium. Nat. Rev. Mol. Cell Biol. 19, 713–730 (2018).

    Article  CAS  PubMed  Google Scholar 

  11. Hernandez-Segura, A., Nehme, J. & Demaria, M. Hallmarks of cellular senescence. Trends Cell Biol. 28, 436–453 (2018).

    Article  CAS  PubMed  Google Scholar 

  12. Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019).

    Article  CAS  PubMed  Google Scholar 

  13. Borghesan, M., Hoogaars, W. M. H., Varela-Eirin, M., Talma, N. & Demaria, M. A senescence-centric view of aging: implications for longevity and disease. Trends Cell Biol. 30, 777–791 (2020).

    Article  CAS  PubMed  Google Scholar 

  14. Walters, H. E. & Yun, M. H. Rising from the ashes: cellular senescence in regeneration. Curr. Opin. Gen. Dev. 64, 94–100 (2020).

    Article  CAS  Google Scholar 

  15. Sasaki, M., Kumazaki, T., Takano, H., Nishiyama, M. & Mitsui, Y. Senescent cells are resistant to death despite low Bcl-2 level. Mech. Ageing Dev. 122, 1695–1706 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Childs, B. G., Baker, D. J., Kirkland, J. L., Campisi, J. & van Deursen, J. M. Senescence and apoptosis: dueling or complementary cell fates?. EMBO Rep. 15, 1139–1153 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ciscato, F. et al. Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+-dependent death of cancer cells. EMBO Rep. 21, e49117 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fouquerel, E. et al. ARTD1/PARP1 negatively regulates glycolysis by inhibiting hexokinase 1 independent of NAD+ depletion. Cell Rep. 8, 1819–1831 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Andrabi, S. A. et al. Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis. Proc. Natl Acad. Sci. USA 111, 10209–10214 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. del Moral, R. M. et al. PARP inhibition attenuates histopathological lesion in ischemia/reperfusion renal mouse model after cold prolonged ischemia. ScientificWorldJournal 2013, 486574 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bonventre, J. V. & Yang, L. Cellular pathophysiology of ischemic acute kidney injury. J. Clin. Invest. 121, 4210–4221 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Fatokun, A. in Apoptosis and Beyond: the Many Ways Cells Die (ed. Radosevich, J.) 535–558 (John Wiley & Sons, 2018).

  23. Andersson, A. et al. PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation. Nucleic Acids Res. 44, 7630–7645 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li, Y. et al. Astragaloside IV reduces neuronal apoptosis and parthanatos in ischemic injury by preserving mitochondrial hexokinase-II. Free Radic. Biol. Med. 131, 251–263 (2019).

    Article  CAS  PubMed  Google Scholar 

  25. Pastorino, J. G. & Hoek, J. B. Regulation of hexokinase binding to VDAC. J. Bioenerg. Biomembr. 40, 171–182 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Murata, M. M. et al. NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival. Mol. Biol. Cell 30, 2584–2597 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Malyala, S., Zhang, Y., Strubbe, J. O. & Bazil, J. N. Calcium phosphate precipitation inhibits mitochondrial energy metabolism. PLoS Comput. Biol. 15, e1006719 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wu, R. et al. Reduction in hexokinase II levels results in decreased cardiac function and altered remodeling after ischemia/reperfusion injury. Circ. Res. 108, 60–69 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Wang, L., Lankhorst, L. & Bernards, R. Exploiting senescence for the treatment of cancer. Nat. Rev. Cancer 22, 340–355 (2022).

    Article  CAS  PubMed  Google Scholar 

  30. Jang, H. R. et al. Poly (ADP-ribose) polymerase inhibitor treatment as a novel therapy attenuating renal ischemia-reperfusion injury. Front. Immunol. 11, 564288 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Berger, N. A. et al. Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. Br. J. Pharmacol. 175, 192–222 (2018).

    Article  CAS  PubMed  Google Scholar 

  32. Melk, A., Schmidt, B. M. W., Vongwiwatana, A., Rayner, D. C. & Halloran, P. F. Increased expression of senescence-associated cell cycle inhibitor p16INK4a in deteriorating renal transplants and diseased native kidney. Am. J. Transplant. 5, 1375–1382 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Kim, S. R. et al. Progressive cellular senescence mediates renal dysfunction in ischemic nephropathy.J. Am. Soc. Nephrol. 32, 1987–2004 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Melk, A. et al. Effects of donor age and cell senescence on kidney allograft survival. Am. J. Transplant. 9, 114–123 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Li, C., Shen, Y., Huang, L., Liu, C. & Wang, J. Senolytic therapy ameliorates renal fibrosis postacute kidney injury by alleviating renal senescence. FASEB J. 35, e21229 (2021).

    CAS  PubMed  Google Scholar 

  36. Megyesi, J., Andrade, L., Vieira, J. M. Jr., Safirstein, R. L. & Price, P. M. Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure. Kidney Int. 60, 2164–2172 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Sieben, C. J., Sturmlechner, I., van de Sluis, B. & van Deursen, J. M. Two-step senescence-focused cancer therapies. Trends Cell Biol. 28, 723–737 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dimri, G. P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Olive, P. L. & Banáth, J. P. The comet assay: a method to measure DNA damage in individual cells. Nat. Protoc. 1, 23–29 (2006).

    Article  CAS  PubMed  Google Scholar 

  40. Bonora, M. et al. Comprehensive analysis of mitochondrial permeability transition pore activity in living cells using fluorescence-imaging-based techniques. Nat. Protoc. 11, 1067–1080 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. Casella, G. et al. Transcriptome signature of cellular senescence. Nucleic Acids Res. 47, 11476 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank M. Koster (UMCG) for helping with the immunostaining, A. Van Oosten (UMCG) for helping with the mouse experiments and the sequencing facility (UMCG) for performing the RNA-seq. This work was supported by grants from the Dutch Cancer Foundation KWF (research grant no. 10989 to M.D.), a Dutch Research Council Vidi Grant no. 09150172010029 (to M.D.) and the Lebanese National Council for Scientific Research-Lebanese University scholarship (to J.N.).

Author information

Authors and Affiliations

  1. European Research Institute for the Biology of Ageing (ERIBA), University of Groningen (RUG), University Medical Center Groningen, Groningen, the Netherlands

    Jamil Nehme, Marta Varela-Eirin, Simone Brandenburg, Abdullah Altulea, Yao Lin & Marco Demaria

  2. Department of Biology, Lebanese University, Beirut, Lebanon

    Jamil Nehme, Lina Mesilmany & Haidar Akl

  3. Université de Lille, Inserm, U1003-PHYCEL-Physiologie Cellulaire, Lille, France

    Lina Mesilmany, Natacha Prevarskaya & Valerio Farfariello

  4. Laboratory of Excellence, Ion Channels Science and Therapeutics, Villeneuve d’Ascq, France

    Lina Mesilmany, Natacha Prevarskaya & Valerio Farfariello

  5. Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

    Mariana Gaya da Costa & Marc Seelen

  6. Department of Pathology & Medical Biology, Pathology Division, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Jan-Luuk Hillebrands & Harry van Goor

  7. Department of Pediatrics, Stanford University, Stanford, CA, USA

    Raya Saab

  8. Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon

    Haidar Akl

Authors
  1. Jamil Nehme
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lina Mesilmany
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marta Varela-Eirin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Simone Brandenburg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdullah Altulea
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yao Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mariana Gaya da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marc Seelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jan-Luuk Hillebrands
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harry van Goor
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Raya Saab
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Haidar Akl
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Natacha Prevarskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Valerio Farfariello
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Marco Demaria
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.N. and M.D. conceptualized the study. J.N., L.M., V.F., J.-L.H., H.G., N.P. and M.D. devised the methodology. J.N., L.M., M.V.-E., A.A., S.B., Y.L., M.G.C. and V.F. carried out the investigation. J.N., L.M., M.V.-E., Y.L., M.G.C. and V.F. visualized the data. M.D. acquired the funding and managed the project. M.S., R.S., N.P., H.A. and M.D. supervised the project. J.N. and M.D. wrote the original paper draft. J.N., J.-L.H., H.G., R.S., N.P., H.A., V.F. and M.D. reviewed and edited the paper.

Corresponding author

Correspondence to Marco Demaria.

Ethics declarations

Competing interests

M.D. is founder and shareholder of Cleara Biotech and an adviser for Oisin Biotechnologies. Neither Cleara Biotech nor Oisin Biotechnologies were involved in the study. The other authors declare no competing interests.

Peer review

Peer review information

Nature Aging thanks David Ferenbach, Valery Krizhanovsky and Satomi Miwa for their contributions to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 PARP1 is downregulated in senescence.

a, The heatmap represents expression levels of genes implicated in oxidative stress induced cell death in multiple types of senescence. b-c, IMR90 human fibroblasts were irradiated for senescence induction or sham treated. 7 days later, cells were analyzed using b, qRT-PCR or c, western blot for the expression of PAPR1 relative to housekeeping; n = 3. d-e, Senescent (irradiated), and proliferating IMR-90 cells were treated with H2O2 (1 mM). d, Cells were stained for PAR polymers after 15 min H2O2 exposure. Quantification was performed on images taken from multiple microscopic fields of view. Scale bar; 150 µm. e, cell survival was measured by using an MTS assay 24 hours after 1 h H2O2 treatment; n = 3. Unpaired two-tailed t-test, data are means ± SD (b, c, d, and e). Dox, doxorubicin. IR, irradiated, Onco, Oncogene-induced. Rep, replicative.

Source data

Extended Data Fig. 2 PARP1 is implicated in cell fate decision upon oxidative stress.

a, IMR90 cells were incubated with the indicated PARP inhibitor or vehicle for 2 hours, followed by H2O2 treatment. Cell survival was measured using MTS assay 24 hours after 1 hour H2O2 treatment; n = 3. b-c, IMR-90 cells were transfected with siRNA against PARP1, PARP2, or control. b, the expression levels of PARP1 and PARP2 were evaluated in the siRNA-transfected cells; n = 3. c, cell survival was measured using MTS assay 24 hours after 1 hour H2O2 treatment; n = 3. d, IMR90 cells were pre-incubated with either PJ34 or a vehicle control for a duration of 2 hours, followed by exposure to 500 µM of peroxynitrite (ONOO-). Subsequently, cell viability was assessed 24 hours after the treatment using MTS assay. e, IMR90 cells were treated with H2O2 then incubated with 5 mM NAD + . 24 h later, cell survival was measured using MTS assay; n = 3. f-g, Cells treated with PJ34 followed by H2O2 or sham, 10 days after the treatment, were either; f, harvested for Western blot analysis to assess p16 protein expression, or g, replated and subjected to γH2AX staining; n = 253 from 3 independent experiments (Scale bar; 50 µm). h-i, cells transfected with siRNA PARP1 were treated with H2O2 or sham. 10 days after the treatment, cells were re-plated and h, incubated with EdU for 24 h hours and stained (n = 3, Scale bar; 150 µm) or i, stained for SA-β-gal (n = 3, Scale bar; 150 µm). j-k, remaining cells from a lethal dose of H2O2, 10 days after the treatment, were re-plated and j, incubated with EdU for 24 hours and stained (n = 3, Scale bar: 150 µm), or k, stained for SA-β-gal (n = 3, Scale bar: 150 µm). One-way ANOVA, data are means ± SD (a,b). Unpaired two-tailed t-test, data are means ± SD (c, d, e, f, h, i, j, and k). Two-tailed Mann-whiteney test, data are means ± SD (g).

Source data

Extended Data Fig. 3 Ca2+ signaling is implicated in the decision between senescence and death.

a, Mean traces of the Fura-2am fluorescence ratio (F340/F380) measured in IMR-90 fibroblast exposed to 125 μM, 500 μM, or 1 mM H2O2. n = 163, 107, and 156 respectively, from 4 biological replicates. b, the bar diagram plot compares the mean rates of Ca2+ uptake in the cytosol, calculated as signal mass per second in cells treated as in a. c-d, IMR-90 human fibroblast cells treated with BAPTA-am followed by H2O2 or sham were re-plated 10 days after the treatment for further analysis. c, cells were analyzed using qRT-PCR for the expression of senescence-associated mRNAs relative to housekeeping (tubulin); n = 6. d, γH2AX staining for detecting persistent DNA damage foci; n = 185. IMR-90 cells were treated with different H2O2 concentrations and for e, incubated with EdU for 24 h hours, and stained (n = 3, Scale bar; 150 µm) or f, stained for SA-β-gal (n = 3, Scale bar; 150 µm), 10 days after treatment; n = 3. g, MTS viability measurement after the treatment with the indicated concentrations of H2O2 in cells pretreated with the Ca2+ ionophore calcimycine (10uM) or sham; n = 3. h, MTS viability measurement following treatment with the specified concentration of peroxynitrite (ONOO-) in cells that were either pretreated with the Ca2+ ionophore calcimycine (10uM) or sham; n = 3. One-way ANOVA, data are means ± SEM (a) and ±SD (e, f, and g). Multiple Two-tailed Mann-Whiteney test, data are mean ± SD (c). Two-tailed Mann-Whiteney test, data are mean ± SD (d). Unpaired two-tailed t-test, data means ± SD (h). BA, BAPTA-AM.

Source data

Extended Data Fig. 4 Hexokinase is involved in PARP-modulated Ca2+ signaling.

a, immunoblot analysis of HK2, along with control proteins VDAC for the mitochondrial fraction and tubulin for the cytosol fraction, using IMR-90 cells treated with the indicated treatments. b, bar diagram comparing the mean of mitochondrial Ca2+ basal levels, calculated as signal mass per second; n = 153 for Control and 203 for HKII overexpressing cells (IMR-90). IMR-90 cells treated with PJ34 or sham for 2 hours were analyzed either c, using qRT-PCR to measure the expression of SERCA2 mRNAs relative to the housekeeping gene (tubulin); n = 6, or d, Immunoblotting to detect the protein levels of SERCA; n = 3. Unpaired two-tailed t-test, data are means ± SD (a, b, and c).

Source data

Extended Data Fig. 5 PARP inhibition promotes early senescence and limits long-term kidney pathology.

a-d, mice were subjected to unilateral kidney IR, either receiving the PARP inhibitor PJ34 (10 mg/kg) or a vehicle control. a, 3 days following the induction of IR, kidney tissues were harvested for subsequent histological staining for the proliferation marker ki-67, n = 6. Scale bar; 100 µm. b, Dual staining with p21 and Periodic Acid-Schiff (PAS). Left panel, representative images. Right panel, quantification of the percentage of p21+ cells with epithelial morphology, n = 4 for vehicle and 5 for PJ34 treated. Scale bar; 10 µm. c-d, kidney tissues were collected 35 days after the initiation of IR to investigate the long-term effects of PARP inhibition following IR. qRT-PCR was used to assess the expression of c, kidney fibrosis markers (n = 10) and d, senescence markers (n = 5). Data were normalized to the corresponding control, with actin serving as the housekeeping gene. Unpaired two-tailed t-test, data are means ± SD (a, b, c and d). IR, ischemia-reperfusion.

Source data

Supplementary information

Supplementary Information

Supplementary Table (primers).

Reporting Summary

Source data

Source Data Fig. 1

Statistical source data.

Source Data Fig. 2

Statistical source data.

Source Data Fig. 3

Statistical source data.

Source Data Fig. 4

Statistical source data.

Source Data Extended Data Fig. 1

Statistical source data.

Source Data Extended Data Fig. 1

Unprocessed immunoblots.

Source Data Extended Data Fig. 2

Statistical source data.

Source Data Extended Data Fig. 2

Unprocessed immunoblots.

Source Data Extended Data Fig. 3

Statistical source data.

Source Data Extended Data Fig. 4

Statistical source data.

Source Data Extended Data Fig. 4a

Unprocessed immunoblots.

Source Data Extended Data Fig. 4b

Unprocessed immunoblots.

Source Data Extended Data Fig. 5

Statistical source data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nehme, J., Mesilmany, L., Varela-Eirin, M. et al. Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00627-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s43587-024-00627-x

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing