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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

Author

Listed:
  • Darren J. Baker

    (Mayo Clinic College of Medicine
    Molecular Biology and Biochemistry, Mayo Clinic College of Medicine
    Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine)

  • Tobias Wijshake

    (Mayo Clinic College of Medicine
    University Medical Center Groningen, Groningen University)

  • Tamar Tchkonia

    (Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine)

  • Nathan K. LeBrasseur

    (Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine
    Physical Medicine and Rehabilitation, Mayo Clinic College of Medicine)

  • Bennett G. Childs

    (Mayo Clinic College of Medicine)

  • Bart van de Sluis

    (University Medical Center Groningen, Groningen University)

  • James L. Kirkland

    (Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine)

  • Jan M. van Deursen

    (Mayo Clinic College of Medicine
    Molecular Biology and Biochemistry, Mayo Clinic College of Medicine
    Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine)

Abstract

Role of cell senescence in ageing Senescent cells accumulate in tissues with age, but it is not known whether they actually cause age-related dysfunction or whether their removal is beneficial. Using a mouse model with a transgene named INK-ATTAC, which allows for the inducible elimination of cells carrying the senescence biomarker p16Ink4a, Baker et al. demonstrate that life-long removal of senescent cells delays the onset of age-related phenotypes. Furthermore, late-life clearance attenuated the progression of already established age-related disorders. This indicates that senescent cells do cause age-related phenotypes and that their removal can prevent or delay age-related tissue dysfunction.

Suggested Citation

  • Darren J. Baker & Tobias Wijshake & Tamar Tchkonia & Nathan K. LeBrasseur & Bennett G. Childs & Bart van de Sluis & James L. Kirkland & Jan M. van Deursen, 2011. "Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders," Nature, Nature, vol. 479(7372), pages 232-236, November.
    • Handle: RePEc:nat:nature:v:479:y:2011:i:7372:d:10.1038_nature10600
    DOI: 10.1038/nature10600
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    Cited by:

    1. Gorshkov, Vyacheslav & Privman, Vladimir & Libert, Sergiy, 2016. "Lattice percolation approach to 3D modeling of tissue aging," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 462(C), pages 207-216.
    2. Jielu Hao Robichaud & Yingyi Zhang & Chuan Chen & Kai He & Yan Huang & Xu Zhang & Xiaobo Sun & Xiaoyu Ma & Gary Hardiman & Ciaran G. Morrison & Zheng Dong & Nathan K. LeBrasseur & Kun Ling & Jinghua H, 2024. "Transiently formed nucleus-to-cilium microtubule arrays mediate senescence initiation in a KIFC3-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Young Hwa Kim & Young-Kyoung Lee & Soon Sang Park & So Hyun Park & So Yeong Eom & Young-Sam Lee & Wonhee John Lee & Juhee Jang & Daeha Seo & Hee Young Kang & Jin Cheol Kim & Su Bin Lim & Gyesoon Yoon , 2023. "Mid-old cells are a potential target for anti-aging interventions in the elderly," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Cox, Lynne S., 2022. "Therapeutic approaches to treat and prevent age-related diseases through understanding the underlying biological drivers of ageing," The Journal of the Economics of Ageing, Elsevier, vol. 23(C).
    5. He Cao & Panpan Yang & Jia Liu & Yan Shao & Honghao Li & Pinglin Lai & Hong Wang & Anling Liu & Bin Guo & Yujin Tang & Xiaochun Bai & Kai Li, 2023. "MYL3 protects chondrocytes from senescence by inhibiting clathrin-mediated endocytosis and activating of Notch signaling," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Yudong Fu & Fan Jiang & Xiao Zhang & Yingyi Pan & Rui Xu & Xiu Liang & Xiaofen Wu & Xingqiang Li & Kaixuan Lin & Ruona Shi & Xiaofei Zhang & Dominique Ferrandon & Jing Liu & Duanqing Pei & Jie Wang & , 2024. "Perturbation of METTL1-mediated tRNA N7- methylguanosine modification induces senescence and aging," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    7. Seoyeon Lee & Mohammad Naimul Islam & Kaveh Boostanpour & Dvir Aran & Guangchun Jin & Stephanie Christenson & Michael A. Matthay & Walter L. Eckalbar & Daryle J. DePianto & Joseph R. Arron & Liam Mage, 2021. "Molecular programs of fibrotic change in aging human lung," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    8. Madison L. Doolittle & Dominik Saul & Japneet Kaur & Jennifer L. Rowsey & Stephanie J. Vos & Kevin D. Pavelko & Joshua N. Farr & David G. Monroe & Sundeep Khosla, 2023. "Multiparametric senescent cell phenotyping reveals targets of senolytic therapy in the aged murine skeleton," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. Xu Zhang & Vesselina M. Pearsall & Chase M. Carver & Elizabeth J. Atkinson & Benjamin D. S. Clarkson & Ethan M. Grund & Michelle Baez-Faria & Kevin D. Pavelko & Jennifer M. Kachergus & Thomas A. White, 2022. "Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Jie Sun & Ming Wang & Yaqi Zhong & Xuan Ma & Shimin Sun & Chenzhong Xu & Linyuan Peng & Guo Li & Liting Zhang & Zuojun Liu & Ding Ai & Baohua Liu, 2022. "A Glb1-2A-mCherry reporter monitors systemic aging and predicts lifespan in middle-aged mice," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Eirini Lionaki & Ilias Gkikas & Ioanna Daskalaki & Maria-Konstantina Ioannidi & Maria I. Klapa & Nektarios Tavernarakis, 2022. "Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    13. Benjamin Assouline & Rachel Kahn & Lutfi Hodali & Reba Condiotti & Yarden Engel & Ela Elyada & Tzlil Mordechai-Heyn & Jason R. Pitarresi & Dikla Atias & Eliana Steinberg & Tirza Bidany-Mizrahi & Esthe, 2024. "Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Sascha Schäuble & Karolin Klement & Shiva Marthandan & Sandra Münch & Ines Heiland & Stefan Schuster & Peter Hemmerich & Stephan Diekmann, 2012. "Quantitative Model of Cell Cycle Arrest and Cellular Senescence in Primary Human Fibroblasts," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-14, August.

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