Senescent cell death as an aging resistance mechanism in naked mole-rat

Yoshimi Kawamura, Kaori Oka, Mayuko Takamori, Yuki Sugiura, Yuki Oiwa, Shusuke Fujioka, Sayuri Homma, Shingo Miyawaki, Minoru Narita, Takaichi Fukuda, Makoto Suematsu, Hidemasa Bono, Hideyuki Okano, Kyoko Miura

Research output: Contribution to journalArticlepeer-review

Abstract

Naked mole-rats (NMRs) are the longest-lived rodents, showing minimal aging phenotypes. An unsolved paradox is that NMRs exhibit low intracellular anti-oxidant defence despite minimal aging. Here, we explained a link between these “contradicting” features by a phenomenon termed “senescent cell death (SCD)”—Senescence induced cell death in NMR cells due to their inherent vulnerability to reactive oxygen species and unique metabolic system. In NMR skin, we observed few senescent cells during aging or after ultraviolet irradiation, suggesting suppression of senescent cell accumulation in NMR tissue. We discovered that senescent NMR-fibroblasts induce SCD through retinoblastoma protein activation accompanied by autophagy dysregulation, increased oxidative damage and accelerated H2O2-releasing metabolic pathways. During senescence, NMR cells showed resistance to metabolic remodelling unlike mice. Our findings provide mechanistic insights into how extraordinary aging resistance is accomplished in NMR. This will contribute to the development of senolytic drugs to regulate age-related diseases.

Original languageEnglish
JournalUnknown Journal
DOIs
Publication statusPublished - 2020 Jul 3

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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