| First Author | Fielder E | Year | 2020 |
| Journal | Aging Cell | Volume | 19 |
| Issue | 10 | Pages | e13188 |
| PubMed ID | 32915495 | Mgi Jnum | J:296943 |
| Mgi Id | MGI:6469380 | Doi | 10.1111/acel.13188 |
| Citation | Fielder E, et al. (2020) Anti-inflammatory treatment rescues memory deficits during aging in nfkb1(-/-) mice. Aging Cell 19(10):e13188 |
| abstractText | 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-kappaB activity (nfkappab1(-/-) ), 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. |
