NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence

Tabata, Sho; Matsuda, Keita; Soeda, Shou et al.

FEBS Journal, 2024, 291(22), 4951-4968

Number of Access:1,006（2025-07-18 17:14 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98127

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Title
NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence
Creator
CreatorName
Tabata, Sho
CreatorName
Matsuda, Keita
NRID
1000040783858 1000040783858
researchmap permalink
shou-soeda shou-soeda
CreatorName
Soeda, Shou
CreatorName
Nagai, Kenshiro
NRID
1000070622166 1000070622166
CreatorName
Izumi, Yoshihiro
NRID
1000030844419 1000030844419
CreatorName
Takahashi, Masatomo
NRID
1000010587794 1000010587794
ORCID
0000-0003-1088-9985 0000-0003-1088-9985
researchmap permalink
yasutaka_motomura yasutaka_motomura
Scopus Author ID
23036180600 23036180600
CreatorName
Motomura, Yasutaka
NRID
1000070869106 1000070869106
researchmap permalink
a-ichikawa-nagasato a-ichikawa-nagasato
CreatorName
Ichikawa Nagasato, Ayaka
NRID
1000090468489 1000090468489
ORCID
0000-0002-7377-1303 0000-0002-7377-1303
researchmap permalink
kazuyomoro kazuyomoro
Scopus Author ID
16638841900 16638841900
CreatorName
Moro, Kazuyo
NRID
1000010432444 1000010432444
researchmap permalink
read0090438 read0090438
CreatorName
Bamba, Takeshi
NRID
1000010342833 1000010342833
ORCID
0000-0002-6210-8223 0000-0002-6210-8223
researchmap permalink
mariko_okada mariko_okada
Scopus Author ID
57194562293 57194562293
CreatorName
Okada, Mariko
Subject
cellular senescence
inflammatory aging
NFκB
nuclear dynamics
SASP
Description
Tabata S., Matsuda K., Soeda S., et al. NFκB dynamics-dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence. FEBS Journal , (2024); https://doi.org/10.1111/febs.17227.
Abstract
Upregulation of nuclear factor κB (NFκB) signaling is a hallmark of aging and a major cause of age-related chronic inflammation. However, its effect on cellular senescence remains unclear. Here, we show that alteration of NFκB nuclear dynamics from oscillatory to sustained by depleting a negative feedback regulator of NFκB pathway, NFκB inhibitor alpha (IκBα), in the presence of tumor necrosis factor α (TNFα) promotes cellular senescence. Sustained NFκB activity enhanced inflammatory gene expression through increased NFκB-DNA binding and slowed the cell cycle. IκBα protein was decreased under replicative or oxidative stress in vitro. Furthermore, a decrease in IκBα protein and an increase in DNA-NFκB binding at the transcription start sites of age-associated genes in aged mouse hearts suggested that nuclear NFκB dynamics may play a critical role in the progression of aging. Our study suggests that nuclear NFκB dynamics-dependent epigenetic changes regulated over time in a living system, possibly through a decrease in IκBα, enhance the expression of inflammatory genes to advance the cells to a senescent state.
Publisher
John Wiley and Sons Inc
Source Title
FEBS Journal
Volume (Issue)
291(22)
Page
4951-4968
Date of Issued
2024-07-16
Language
English
Handle URL
https://hdl.handle.net/11094/98127
PISSN
1742464X
eISSN
17424658
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1111/febs.17227
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article