Abstract
BackgroundInflammaging is a condition of chronic low-grade inflammation due to the aging process and is associated with a variety of chronic diseases. Monocytes are innate immune cells which contribute to inflammation and are dysregulated during aging, demonstrated reduced phagocytosis, increased inflammation, and alterations in subset proportions. Metabolism is known to determine immune cell function, with quiescent and anti-inflammatory cells primarily relying on fatty acid oxidation, while activated and inflammatory cells primarily rely on glycolysis. We have previously shown an age-related decrease in mitochondrial respiratory capacity in monocytes, so we hypothesized here that a compensatory shift toward glycolysis would occur which would also exacerbate inflammation.ResultsUsing Seahorse assays, we profiled glycolysis in classical monocytes isolated from older (60–80 yr) and younger (18–35 yr) adults. Aging did not affect parameters of basal glycolysis in the glycolysis stress test, nor did it alter glycolytic activation early (2 h) or later (24 h) post-LPS stimulation. Cytokine gene expression was unchanged between aged and young subjects at 2 h post-LPS but was reduced in older subjects at 24 h post-LPS either significantly (IL1B) or near-significantly (IL6, IL10).ConclusionsAging appears not to affect glycolytic metabolism ex vivo in classical monocytes, but may reduce cytokine expression at later timepoints. Studies examining monocytes stimulated with age-altered circulating factors or with other pattern recognition receptor agonists may shed further light on monocyte metabolism as a determinant of immunosenescence and inflammaging.
Highlights
The adult population of the United States is aging at an increasing rate, with nearly 20% of U.S adults expected to be over age 65 by 2030 [1]
Extracellular flux assays and cytokine expression To determine the effect of aging on parameters of glycolysis absent stimulation, we conducted a Seahorse
We have previously demonstrated that aging impairs mitochondrial respiratory capacity in classical monocytes [16]
Summary
The adult population of the United States is aging at an increasing rate, with nearly 20% of U.S adults expected to be over age 65 by 2030 [1]. A key player in age-related innate immune dysfunction is the monocyte, a circulating cell with important functions including antigen presentation, phagocytosis, and cytokine production [6]. Dysregulation of monocyte phenotype and/or function is associated with chronic diseases including but not limited to various cancers [7] and cardiovascular and renal diseases [8, 9]. Aging alters monocyte subpopulation proportions and integrin expression patterns and increases basal cytokine production [10, 11]. Monocytes are innate immune cells which contribute to inflammation and are dysregulated during aging, demonstrated reduced phagocytosis, increased inflammation, and alterations in subset proportions. We have previously shown an age-related decrease in mitochondrial respiratory capacity in monocytes, so we hypothesized here that a compensatory shift toward glycolysis would occur which would exacerbate inflammation
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