Abstract
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.
Original language | English (US) |
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Article number | e13188 |
Journal | Aging Cell |
Volume | 19 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2020 |
Keywords
- aging
- cognitive decline
- hippocampus
- memory
- neuroinflammation
- senescence
ASJC Scopus subject areas
- Aging
- Cell Biology