Abstract
Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and phosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.
Highlights
The concept of frailty is gaining traction as an independent clinical syndrome to explain differential outcomes in older adults 1
The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission
We propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults
Summary
The concept of frailty is gaining traction as an independent clinical syndrome to explain differential outcomes in older adults 1. Slowness, and poor balance are some of the main physical manifestations of frailty, which is associated with adverse events that can lead to a dramatic decline in the quality of life and independence 2. Identifying populations at-risk and exploratively identifying potential early and/or predictive biomarkers of age-associated changes that could guide effective health promotion interventions are especially relevant 4. One of these strategies has been the investigation of the metabolome, the complete set of molecular weight molecules (metabolites) present in a biological sample. Metabolomic approaches that analyze changes in metabolite levels seem promising for the development of non-invasive diagnostic biomarkers of the frailty phenotype, yet data from older adults at hospital admission are sparse
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