1H NMR metabolomics and lipidomics analysis of neutrophils reveals biomarkers of ageing, inflammageing and frailty

ABSTRACT:

Background: Neutrophil function declines with age, but little is known about the changes in neutrophil metabolism that take place in older people and people with frailty. We used 1H-NMR spectroscopy to investigate the metabolic profiles of neutrophils from healthy younger (HY) and older (HO) people and older people with frailty (FR), to identify metabolites and metabolic pathways altered with healthy ageing and ageing with frailty. We also compared FR metabolites to rheumatoid arthritis (RA) neutrophils to identify markers of inflammation in FR neutrophils.

 

Methods: 1H-NMR spectroscopy was performed on polar and lipid metabolites extracted from blood neutrophils. Polar metabolites were annotated using Chenomx prior to univariate (ANOVA, Tukey’s adjusted p-value<0.05) and supervised (partial least square discriminant analysis, PLS-DA) multivariate analyses in R (v4.4.1). Lipid metabolites were analysed as spectral bins. Metabolite enrichment analysis was performed using Metaboanalyst (v6) against the small molecule pathway database (SMPDB).

 

Results: ANOVA identified 17 polar metabolites significantly different across the participant groups (adj. p<0.05). Three polar metabolites were significantly different in FR vs HO neutrophils, with NADP being higher in FR and lysine and choline being lower. NADP was uniquely elevated in FR compared to HO, HY and RA neutrophils. Seven metabolites were significantly different between HO and HY neutrophils, and only 2 metabolites were different between FR and RA neutrophils, identifying underlying similarities between FR and RA that may be driven by inflammation. Four lipid peaks were significantly different between FR and HY neutrophils. These were attributed to total cholesterol and arachidonic acid.

 

Conclusions: This is the first study of polar and lipid metabolism in neutrophils from people with frailty. Our results provide evidence that metabolic signalling pathways involved in neutrophil activation, oxidative stress and lipid metabolism are altered during healthy ageing and ageing with frailty, and we identify NADP as a unique biomarker of altered neutrophil function in people with frailty.

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR) -

PROVIDER: MTBLS6055 | MetaboLights | 2026-03-26

REPOSITORIES: MetaboLights