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. NMR fibroblasts uniquely accumulated serotonin and were inherently vulnerable to hydrogen peroxide (H2O2). After activation of the INK4a-RB pathway, NMR fibroblasts increased monoamine oxidase levels, leading to serotonin oxidization and H2O2 prod

SUBMITTER: Dr. Yoshimi Kawamura 

PROVIDER: S-SCDT-10_15252-EMBJ_2022111133 | biostudies-other |

REPOSITORIES: biostudies-other