Alterations of monocyte NF-kappa B p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults

Research output: Contribution to journalJournal articleResearchpeer-review

  • Juliette Tavenier
  • Line Jee Hartmann Rasmussen
  • Morten Baltzer Houlind
  • Aino Leegaard Andersen
  • Inge Panum
  • Andersen, Ove
  • Petersen, Janne
  • Anne Langkilde
  • Jan O. Nehlin

Background: Altered monocyte NF-kappa B signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-kappa B signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults.

Methods: We used data from: 52 older (>= 65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20-35 years). Using flow cytometry, we assessed basal NF-kappa B phosphorylation (pNF-kappa B p65/RelA; Ser529) and induction of pNF-kappa B following stimulation with LPS or TNF-alpha in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-alpha, and soluble urokinase plasminogen activator receptor.

Results: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-kappa B levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90,p <0.0001), and reduced pNF-kappa B induction in response to LPS (mean pNF-kappa B MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15,p = 0.05) and TNF-alpha stimulation (0.02, 95% CI: - 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12,p <0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-kappa B MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70-86;p = 0.72). Older Controls had reduced pNF-kappa B induction in response to LPS and TNF-alpha compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44,p <0.0001; and TNF-alpha: 0.33, 95% CI: 0.27 to 0.40,p <0.0001). In Older Controls, basal pNF-kappa B MFI was associated with FI-OutRef (p = 0.02).

Conclusions: Increased basal pNF-kappa B activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-kappa B activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

Original languageEnglish
Article number25
JournalImmunity and Ageing
Volume17
Issue number1
Number of pages16
ISSN1742-4933
DOIs
Publication statusPublished - 2020

    Research areas

  • Aging, Monocyte, NF-kappa B, Immunosenescence, Chronic inflammation, Inflammaging, NECROSIS-FACTOR-ALPHA, HLA-DR EXPRESSION, DENDRITIC CELLS, CHRONIC INFLAMMATION, FUNCTIONAL DECLINE, UNITED-STATES, PHOSPHORYLATION, EMERGENCY, RESPONSES, DISEASE

ID: 248935970