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Metabolic phenotyping using kinetic measurements in young and older healthy adults.

ABSTRACT: BACKGROUND:The aging process is often associated with the presence of sarcopenia. Although changes in the plasma concentration of several amino acids have been observed in older adults, it remains unclear whether these changes are related to disturbances in whole body production and/or interconversions. METHODS:We studied 10 healthy young (~22.7y) and 17 older adults (~64.8y) by administering a mixture of stable amino acid tracers in a pulse and in a primed constant infusion. We calculated whole body production (WBP) and metabolite to metabolite interconversions. In addition, we measured body composition, muscle function, and provided questionnaires to assess daily dietary intake, physical activity, mood (anxiety, depression) and markers of cognitive function. Plasma enrichments and metabolite concentrations were measured by GC- and LC-MS/MS and statistics were performed by student t-test. RESULTS:Older adults had a 11% higher body mass index (p=0.04) and 27% reduced peak leg extension force (p=0.02) than the younger group, but comparable values for muscle mass, mood and cognitive function. Although small differences in several plasma amino acid concentrations were observed, we found older adults had about 40% higher values of WBP for glutamine (221±27 vs. 305±21?mol/kgffm/h, p=0.03) and tau-methylhistidine (0.15±0.01 vs. 0.21±0.02?mol/kgffm/h, p=0.04), 26% lower WBP value for arginine (59±4 vs. 44±4?mol/kgffm/h, p=0.02) and a reduction in WBP (50%; 1.23±0.15 vs. 0.69±0.06?mol/kgffm/h, p=0.001) and concentration (25%; 3.5±0.3?mol/l vs. 2.6±0.2?mol/l, p=0.01) for ?-Hydroxy ?-Methylbutyrate. No differences were observed in protein catabolism. Clearance of arginine was decreased (27%, p=0.03) and clearance of glutamine (58%, p=0.01), leucine (67%, p=0.001) and KIC (76%, p=0.004) were increased in older adults. CONCLUSIONS:Specific differences exist between young and older adults in amino acid metabolism.

SUBMITTER: Deutz NEP

PROVIDER: S-EPMC5732887 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Metabolic phenotyping using kinetic measurements in young and older healthy adults.

Deutz Nicolaas E P NEP Thaden John J JJ Ten Have Gabriella A M GAM Walker Dillon K DK Engelen Mariëlle P K J MPKJ

Metabolism: clinical and experimental 20171003

<h4>Background</h4>The aging process is often associated with the presence of sarcopenia. Although changes in the plasma concentration of several amino acids have been observed in older adults, it remains unclear whether these changes are related to disturbances in whole body production and/or interconversions.<h4>Methods</h4>We studied 10 healthy young (~22.7y) and 17 older adults (~64.8y) by administering a mixture of stable amino acid tracers in a pulse and in a primed constant infusion. We c ...[more]

PMID: 28986165

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Project description:BackgroundWhereas cardiovascular disease (CVD) metrics define risk in individuals >40 years of age, the earliest lesions of CVD appear well before this age. Despite the role of metabolism in CVD antecedents, studies in younger, biracial populations to define precise metabolic risk phenotypes are lacking.MethodsWe studied 2330 White and Black young adults (mean age, 32 years; 45% Black) in the CARDIA study (Coronary Artery Risk Development in Young Adults) to identify metabolite profiles associated with an adverse CVD phenome (myocardial structure/function, fitness, vascular calcification), mechanisms, and outcomes over 2 decades. Statistical learning methods (elastic nets/principal components analysis) and Cox regression generated parsimonious, metabolite-based risk scores validated in >1800 individuals in the Framingham Heart Study.ResultsIn the CARDIA study, metabolite profiles quantified in early adulthood were associated with subclinical CVD development over 20 years, specifying known and novel pathways of CVD (eg, transcriptional regulation, brain-derived neurotrophic factor, nitric oxide, renin-angiotensin). We found 2 multiparametric, metabolite-based scores linked independently to vascular and myocardial health, with metabolites included in each score specifying microbial metabolism, hepatic steatosis, oxidative stress, nitric oxide modulation, and collagen metabolism. The metabolite-based vascular scores were lower in men, and myocardial scores were lower in Black participants. Over a nearly 25-year median follow-up in CARDIA, the metabolite-based vascular score (hazard ratio, 0.68 per SD [95% CI, 0.50-0.92]; P=0.01) and myocardial score (hazard ratio, 0.60 per SD [95% CI, 0.45-0.80]; P=0.0005) in the third and fourth decades of life were associated with clinical CVD with a synergistic association with outcome (Pinteraction=0.009). We replicated these findings in 1898 individuals in the Framingham Heart Study over 2 decades, with a similar association with outcome (including interaction), reclassification, and discrimination. In the Framingham Heart Study, the metabolite scores exhibited an age interaction (P=0.0004 for a combined myocardial-vascular score with incident CVD), such that young adults with poorer metabolite-based health scores had highest hazard of future CVD.ConclusionsMetabolic signatures of myocardial and vascular health in young adulthood specify known/novel pathways of metabolic dysfunction relevant to CVD, associated with outcome in 2 independent cohorts. Efforts to include precision measures of metabolic health in risk stratification to interrupt CVD at its earliest stage are warranted.

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Metabolic phenotyping using kinetic measurements in young and older healthy adults.

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Metabolic phenotyping using kinetic measurements in young and older healthy adults.

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