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Impaired immune surveillance accelerates accumulation of senescent cells and aging

Author

Listed:
  • Yossi Ovadya

    (The Weizmann Institute of Science)

  • Tomer Landsberger

    (The Weizmann Institute of Science)

  • Hanna Leins

    (Ulm University
    University Hospital of Ulm)

  • Ezra Vadai

    (The Weizmann Institute of Science)

  • Hilah Gal

    (The Weizmann Institute of Science)

  • Anat Biran

    (The Weizmann Institute of Science)

  • Reut Yosef

    (The Weizmann Institute of Science)

  • Adi Sagiv

    (The Weizmann Institute of Science)

  • Amit Agrawal

    (The Weizmann Institute of Science)

  • Alon Shapira

    (The Weizmann Institute of Science)

  • Joseph Windheim

    (The Weizmann Institute of Science)

  • Michael Tsoory

    (The Weizmann Institute of Science)

  • Reinhold Schirmbeck

    (University Hospital of Ulm)

  • Ido Amit

    (The Weizmann Institute of Science)

  • Hartmut Geiger

    (Ulm University
    Experimental Hematology and Cancer Biology Cincinnati Children’s Hospital Medical Center)

  • Valery Krizhanovsky

    (The Weizmann Institute of Science)

Abstract

Cellular senescence is a stress response that imposes stable cell-cycle arrest in damaged cells, preventing their propagation in tissues. However, senescent cells accumulate in tissues in advanced age, where they might promote tissue degeneration and malignant transformation. The extent of immune-system involvement in regulating age-related accumulation of senescent cells, and its consequences, are unknown. Here we show that Prf1−/− mice with impaired cell cytotoxicity exhibit both higher senescent-cell tissue burden and chronic inflammation. They suffer from multiple age-related disorders and lower survival. Strikingly, pharmacological elimination of senescent-cells by ABT-737 partially alleviates accelerated aging phenotype in these mice. In LMNA+/G609G progeroid mice, impaired cell cytotoxicity further promotes senescent-cell accumulation and shortens lifespan. ABT-737 administration during the second half of life of these progeroid mice abrogates senescence signature and increases median survival. Our findings shed new light on mechanisms governing senescent-cell presence in aging, and could motivate new strategies for regenerative medicine.

Suggested Citation

  • Yossi Ovadya & Tomer Landsberger & Hanna Leins & Ezra Vadai & Hilah Gal & Anat Biran & Reut Yosef & Adi Sagiv & Amit Agrawal & Alon Shapira & Joseph Windheim & Michael Tsoory & Reinhold Schirmbeck & I, 2018. "Impaired immune surveillance accelerates accumulation of senescent cells and aging," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07825-3
    DOI: 10.1038/s41467-018-07825-3
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    Cited by:

    1. Carlos Anerillas & Allison B. Herman & Rachel Munk & Amanda Garrido & Kwan-Wood Gabriel Lam & Matthew J. Payea & Martina Rossi & Dimitrios Tsitsipatis & Jennifer L. Martindale & Yulan Piao & Krystyna , 2022. "A BDNF-TrkB autocrine loop enhances senescent cell viability," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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