Open AccessAge‐associated changes in long‐chain fatty acid profile during healthy aging promote pro‐inflammatory monocyte polarization via PPAR γ
Author(s) -
Pararasa Chathyan,
Ikwuobe John,
Shigdar Shahjahan,
Boukouvalas Alexis,
Nabney Ian T.,
Brown James E.,
Devitt Andrew,
Bailey Clifford J.,
Bennett Stuart J.,
Griffiths Helen R.
Publication year - 2016
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12416
Subject(s) - endocrinology , medicine , biology , monocyte , inflammation , ceramide , saturated fatty acid , tumor necrosis factor alpha , oxidative stress , fatty acid , immunology , biochemistry , apoptosis
Summary Differences in lipid metabolism associate with age‐related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids ( FA s) initiate pro‐inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age‐associated changes in individual FA s in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FA s by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FA s, age and cytokines. We showed that plasma saturated, poly‐ and mono‐unsaturated FA s increase with age. Circulating TNF ‐α and IL ‐6 concentrations increased with age, whereas IL ‐10 and TGF ‐β1 concentrations decreased. Oxidation of Mito SOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FA s, indicative of their metabolic relationships. Higher levels of the saturated FA s C18:0 and C24:0 were associated with lower TGF ‐β1 concentrations, and higher C16:0 were associated with higher TNF ‐α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP 1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro‐inflammatory cytokines in response to phorbol myristate acetate‐induced differentiation through ceramide‐dependent inhibition of PPAR γ activity. Conversely, C18:1 primed a pro‐resolving macrophage which was PPAR γ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti‐inflammatory macrophages through metabolic reprogramming.