Impaired immune surveillance accelerates accumulation of senescent cells and aging

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, Ido Amit, Hartmut Geiger, Valery Krizhanovsky

Research output: Contribution to journalArticlepeer-review

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 senescentcell presence in aging, and could motivate new strategies for regenerative medicine.

Original languageEnglish
Article number5435
Number of pages15
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 21 Dec 2018

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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