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Nat Commun. 2018 Dec 21;9(1):5435. doi: 10.1038/s41467-018-07825-3.

Impaired immune surveillance accelerates accumulation of senescent cells and aging.

Author information

1
Department of Molecular Cell Biology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
2
Department of Immunology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
3
Institute of Molecular Medicine, Stem Cell and Aging, Ulm University, Ulm, 89081, Germany.
4
Department of Internal Medicine I, University Hospital of Ulm, Ulm, 89081, Germany.
5
Department of Veterinary Resources, The Weizmann Institute of Science, 76100, Rehovot, Israel.
6
Experimental Hematology and Cancer Biology Cincinnati Children's Hospital Medical Center, 45229, Cincinnati, OH, USA.
7
Department of Molecular Cell Biology, The Weizmann Institute of Science, 76100, Rehovot, Israel. valery.krizhanovsky@weizmann.ac.il.

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.

PMID:
30575733
PMCID:
PMC6303397
DOI:
10.1038/s41467-018-07825-3
[Indexed for MEDLINE]
Free PMC Article

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