Metabolomic response to acute resistance exercise in healthy older adults by 1H-NMR

Abstract

Background: The favorable health-promoting adaptations to exercise result from cumulative responses to individual bouts of physical activity. Older adults often exhibit anabolic resistance; a phenomenon whereby the anabolic responses to exercise and nutrition are attenuated in skeletal muscle. The mechanisms contributing to age-related anabolic resistance are emerging, but our understanding of how chronological age influences responsiveness to exercise is incomplete. The objective was to determine the effects of healthy aging on peripheral blood metabolomic response to a single bout of resistance exercise and whether any metabolites in circulation are predictive of anabolic response in skeletal muscle.

Methods: Thirty young (20-35 years) and 49 older (65-85 years) men and women were studied in a cross-sectional manner. Participants completed a single bout of resistance exercise consisting of eight sets of 10 repetitions of unilateral knee extension at 70% of one-repetition maximum. Blood samples were collected before exercise, immediately post exercise, and 30-, 90-, and 180-minutes into recovery. Proton nuclear magnetic resonance spectroscopy was used to profile circulating metabolites at all timepoints. Serial muscle biopsies were collected for measuring muscle protein synthesis rates.

Results: Our analysis revealed that one bout of resistance exercise elicits significant changes in 26 of 33 measured plasma metabolites, reflecting alterations in several biological processes. Furthermore, 12 metabolites demonstrated significant interactions between exercise and age, including organic acids, amino acids, ketones, and keto-acids, which exhibited distinct responses to exercise in young and older adults. Pre-exercise histidine and sarcosine were negatively associated with muscle protein synthesis, as was the pre/post-exercise fold change in plasma histidine.

Conclusions: This study demonstrates that while many exercise-responsive metabolites change similarly in young and older adults, several demonstrate age-dependent changes even in the absence of evidence of sarcopenia or frailty.

Trial registration: Clinical trial registry: ClinicalTrials.gov NCT03350906.

Fig 1. Changes in plasma carbohydrate, TCA cycle intermediates, and ketone body metabolites in young (n = 30) and older (n = 49) adults pre and post resistance exercise.

Values are shown as mean and 95% CIs of non-transformed data, with (θ) denoting significant (p-value < 0.05) difference between young and older groups at baseline, (*) representing significant effect of time from baseline, (φ) representing age and time interaction, found by LMM. Pre-ex: pre-exercise, IPE: immediately post exercise.

Fig 2. Changes in plasma glucogenic and biogenic amines in young (n = 30) and older (n = 49) adults pre and post resistance exercise.

Values are shown as mean and 95% CIs of non-transformed data, with (θ) denoting significant (p-value < 0.05) difference between young and older groups at baseline, (*) representing significant effect of time from baseline, (φ) representing age and time interaction, found by LMM. Pre-ex: pre-exercise, IPE: immediately post exercise.

Fig 3

Changes in other amino acids and metabolites (A-E), and fold-change (F) pre and post resistance exercise in young (n = 30) and older (n = 49) adults. Values are shown as mean and 95% CIs of non-transformed data, with (θ) denoting significant (p-value < 0.05) difference between young and older groups at baseline, (*) representing significant effect of time from baseline, (φ) representing age and time interaction, found by LMM. Pre-ex: pre-exercise, IPE: immediately post exercise.

Fig 4. Correlation between muscle protein synthesis rates and plasma metabolite levels.

The heatmap in panel A provides the correlation coefficients between muscle fractional synthesis rate (FSR) and metabolite concentrations at each timepoint. Of these, sarcosine (B) and histidine (C) concentrations at rest were significantly negatively associated with FSR. There was also a significant negative association between FSR and the fold change (FC) in plasma histidine from pre-exercise to immediate post-exercise (D). Red color represents positive Pearson correlation coefficients while blue color represents negative correlation. Dotted lines represent 95% confidence intervals for regression analyses in panels B, C, and D.