Differential plasma protein expression after ingestion of essential amino acid-based dietary supplement verses whey protein in low physical functioning older adults

Abstract

In a recent randomized, double-blind, placebo-controlled trial, we were able to demonstrate the superiority of a dietary supplement composed of essential amino acids (EAAs) over whey protein, in older adults with low physical function. In this paper, we describe the comparative plasma protein expression in the same subject groups of EAAs vs whey. The plasma proteomics data was generated using SOMA scan assay. A total of twenty proteins were found to be differentially expressed in both groups with a 1.5-fold change. Notably, five proteins showed a significantly higher fold change expression in the EAA group which included adenylate kinase isoenzyme 1, casein kinase II 2-alpha, Nascent polypeptide-associated complex subunit alpha, peroxiredoxin-1, and peroxiredoxin-6. These five proteins might have played a significant role in providing energy for the improved cardiac and muscle strength of older adults with LPF. On the other hand, fifteen proteins showed slightly lower fold change expression in the EAA group. Some of these 15 proteins regulate metabolism and were found to be associated with inflammation or other comorbidities. Gene Ontology (GO) enrichment analysis showed the association of these proteins with several biological processes. Furthermore, protein-protein interaction network analysis also showed distinct networks between upregulated and downregulated proteins. In conclusion, the important biological roles of the upregulated proteins plus better physical function of participants in the EAAs vs whey group demonstrated that EAAs have the potential to improve muscle strength and physical function in older adults. This study was registered with ClinicalTrials.gov: NCT03424265 "Nutritional interventions in heart failure."

Keywords: Aging; Essential amino acids; Nutrition; Protein expression; Whey protein.

Fig. 1

Volcano plot showed the differential protein expression in the blood plasma samples obtained from older adults after 12 weeks of EAAs vs whey protein consumption using a 1.5-fold change expression. Red dots on the right-hand side indicate upregulation and on the left-hand side indicate downregulation and black dots indicate no significant change in protein expression levels based on an absolute log2 fold change greater than 0.585 or less than − 0.585, indicates 1.5-fold change expression with − log10 p-value greater than 1.3

Fig. 2

Heat map plot for the expression of the differentially expressed proteins in EAAs and whey group in which red color represents the high value and blue color as low value

Fig. 3

Dendrogram showing clustered analysis of significantly expressed proteins in EAAs and whey group

Fig. 4

Pie Chart showing the functional classification of differentially expressed proteins in EAAs vs whey group using Gene Ontology (GO) enrichment analysis through PANTHER-classification system

Fig. 5

Protein–protein interactions using STRING database among all the 20 differentially expressed proteins extracted from 1.5-fold change expression among EAAs vs whey groups

Fig. 6

6 MW (ft) Change from baseline: mean ± SE. *p < 0.05 by the one-sample t test for the whey group’s 6 MW (ft) change from baseline 12 weeks. **p < 0.01 by the signed rank test for the EAA group’s 6 MW (ft) change from baseline 12 weeks. + p < 0.01 by the Mann–Whitney U test for the group comparison of change from baseline at 12 weeks

Fig. 7

Schematic illustrating the process by which EAA supplementation improved physical functioning in older adults