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Lookup NU author(s): Dr Edward FielderORCiD, Dr Clare Tweedy, Dr Caroline WilsonORCiD, Professor Fiona OakleyORCiD, Dr Fiona LeBeauORCiD, Dr Joao Passos, Professor Derek Mann, Professor Thomas von Zglinicki, Dr Diana JurkORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. Chronic inflammation is a common feature of many age-related conditions including neurodegenerative diseases such as Alzheimer's disease. Cellular senescence is a state of irreversible cell-cycle arrest, thought to contribute to neurodegenerative diseases partially via induction of a chronic pro-inflammatory phenotype. In this study, we used a mouse model of genetically enhanced NF-κB activity (nfκb1−/−), characterized by low-grade chronic inflammation and premature aging, to investigate the impact of inflammaging on cognitive decline. We found that during aging, nfkb1−/− mice show an early onset of memory loss, combined with enhanced neuroinflammation and increased frequency of senescent cells in the hippocampus and cerebellum. Electrophysiological measurements in the hippocampus of nfkb1−/− mice in vitro revealed deficits in gamma frequency oscillations, which could explain the decline in memory capacity. Importantly, treatment with the nonsteroidal anti-inflammatory drug (NASID) ibuprofen reduced neuroinflammation and senescent cell burden resulting in significant improvements in cognitive function and gamma frequency oscillations. These data support the hypothesis that chronic inflammation is a causal factor in the cognitive decline observed during aging.
Author(s): Fielder E, Tweedy C, Wilson C, Oakley F, LeBeau FEN, Passos JF, Mann DA, von Zglinicki T, Jurk D
Publication type: Article
Publication status: Published
Journal: Aging Cell
Year: 2020
Volume: 19
Issue: 10
Print publication date: 01/10/2020
Online publication date: 11/09/2020
Acceptance date: 14/06/2020
Date deposited: 20/11/2020
ISSN (print): 1474-9718
ISSN (electronic): 1474-9726
Publisher: Wiley-Blackwell
URL: https://doi.org/10.1111/acel.13188
DOI: 10.1111/acel.13188
PubMed id: 32915495
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