Integrative perspective of the healthy aging process considering the metabolome, cardiac autonomic modulation and cardiorespiratory fitness evaluated in age groups

Abstract

The aging process causes changes at all organic levels. Although metabolism, cardiac autonomic modulation (CAM), and cardiorespiratory fitness (CRF) are widely studied as a function of age, they are mainly studied in isolation, thus making it difficult to perceive their concomitant variations. This study aimed to investigate the integrated changes that occur in the metabolome, CAM, and CRF throughout aging in apparently healthy individuals. The subjects (n = 118) were divided into five groups according to age (20–29, 30–39, 40–49, 50–59, and 60–70 years old) and underwent blood collection, autonomic assessment, and a cardiopulmonary exercise test for metabolomics analysis using mass spectrometry and nuclear magnetic resonance, cardiac autonomic modulation analysis, and CRF by peak oxygen consumption analysis, respectively. The Tukey’s post hoc and effect size with confidence interval were used for variables with a significant one-way ANOVA effect (P < 0.01). The main changes were in the oldest age group, where the CRF, valine, leucine, isoleucine, 3-hydroxyisobutyrate, and CAM reduced and hippuric acid increased. The results suggest significant changes in the metabolome, CAM, and CRF after the age of sixty as a consequence of aging impairments, but with some changes in the metabolic profile that may be favorable to mitigate the aging deleterious effects.

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“…All NMR spectra were processed with 0.3 Hz line broadening (lb). The identification of the most significant compounds, initially characterized using Chenomx software, was supported by the utilization of 2D experiments such as Hetero Single Quantum Coherence, Heteronuclear Multiple Bond Correlation, and COrrelated SpectroscopY (COSY), with parameters based on previous studies 17,18 …”

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“…Venous blood samples were collected at rest, after 12 h of fasting, always in the morning (between 7 and 10 a.m.), by puncture of the antecubital vein in vacuum serum separator tubes (S-Monovette 4.9 mL, Sarstedt, Germany). After 30 min at room temperature, the blood samples were centrifuged at 1450× g for 10 min (Sorvall ST Benchtop Centrifuge, Thermo Scientific, Waltham, MA, USA), then serum aliquots were collected and stored at −80 • C until further analysis [61]. All participants were instructed to avoid high-intensity exercises, stimulating foods and drinks (coffee, energy drinks, chocolate, and foods with a lot of sugar), alcoholic beverages, and supplements on the day before blood collection [48].…”

“…The sample preparation for the 1 H NMR-based metabolomics was conducted according previous studies [48,61]. In brief, 3 kDa filters (Amicon Ultra) were washed five times with 500 µL of Milli-Q water, followed by centrifugation at 14,000× g for 5 min at 4 • C, and spinning (filter reverse and rotation at 7500× g for 60 s) to eliminate residual Milli-Q water.…”

“…The sample preparation for the UHPLC-HRMS/MS-based metabolomics was carried out according to previous studies [48,61]. Serum samples, previously stored at −80 • C, were thawed on ice and vortexed for 15 s. Afterwards, 450 µL of cold methanol was added to 150 µL of serum sample in a microtube to induce protein precipitation and metabolite extraction.…”

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