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


ABSTRACT:

Background

Altered monocyte NF-?B signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-?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-?B phosphorylation (pNF-?B p65/RelA; Ser529) and induction of pNF-?B following stimulation with LPS or TNF-? in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-?, 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-?B levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90, p ConclusionsIncreased basal pNF-?B activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-?B activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

SUBMITTER: Tavenier J 

PROVIDER: S-EPMC7938715 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Tavenier Juliette J   Rasmussen Line Jee Hartmann LJH   Houlind Morten Baltzer MB   Andersen Aino Leegaard AL   Panum Inge I   Andersen Ove O   Petersen Janne J   Langkilde Anne A   Nehlin Jan O JO  

Immunity & ageing : I & A 20200904 1


<h4>Background</h4>Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults.<h4>Methods</h4>We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- a  ...[more]

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