Cellular senescence induction leads to progressive cell death via the INK4a-RB pathway in naked mole-rats.

ABSTRACT: Naked mole-rats (NMRs) have exceptional longevity and are resistant to age-related physiological decline and diseases. Given the role of cellular senescence in aging, we postulated that NMRs possess unidentified species-specific mechanisms to prevent senescent cell accumulation. Here, we show that upon induction of cellular senescence, NMR fibroblasts underwent delayed and progressive cell death that required activation of the INK4a-retinoblastoma protein (RB) pathway (termed "INK4a-RB cell death"), a phenomenon not observed in mouse fibroblasts. Naked mole-rat fibroblasts uniquely accumulated serotonin and were inherently vulnerable to hydrogen peroxide (H₂ O₂ ). After activation of the INK4a-RB pathway, NMR fibroblasts increased monoamine oxidase levels, leading to

SUBMITTER: Kawamura Y 

PROVIDER: S-EPMC10425838 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature