In:
The EMBO Journal, EMBO, Vol. 42, No. 16 ( 2023-08-15)
Abstract:
image Naked mole‐rats are the longest‐lived rodents, known to exhibit resistance to aging and related diseases. This study demonstrates that naked mole‐rat cells have a unique response, undergoing cell death upon induction of cellular senescence, that is not observed in the mouse and could represent a species‐specific method of senescent cell removal. Naked mole‐rat (NMR) fibroblasts undergo progressive cell death upon induction of cellular senescence through activation of the INK4a‐retinoblastoma protein (RB) pathway (INK4a‐RB cell death). INK4a‐RB cell death induction in NMR fibroblasts is independent of p53 activity. NMR fibroblasts uniquely accumulate serotonin and are inherently vulnerable to hydrogen peroxide (H 2 O 2 ). INK4a‐RB pathway activation in NMR fibroblasts leads to monoamine oxidase‐dependent serotonin oxidization and H 2 O 2 production, resulting in an increased oxidative damage and activation of cell death. In the NMR lung, induction of cellular senescence leads to delayed, progressive cell death mediated by monoamine oxidase activity, which contributes to preventing senescent cell accumulation, consistent with in vitro findings.
Type of Medium:
Online Resource
ISSN:
0261-4189
,
1460-2075
DOI:
10.15252/embj.2022111133
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
1467419-1
detail.hit.zdb_id:
586044-1
SSG:
12