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Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study.

ABSTRACT: Age-related declines in physical performance predict cognitive impairment, disability, chronic disease exacerbation, and mortality. We conducted a metabolome-wide association study of physical performance among Bogalusa Heart Study participants. Bonferroni corrected multivariate-adjusted linear regression was employed to examine cross-sectional associations between single metabolites and baseline gait speed (N=1,227) and grip strength (N=1,164). In a sub-sample of participants with repeated assessments of gait speed (N=282) and grip strength (N=201), significant metabolites from the cross-sectional analyses were tested for association with change in physical performance over 2.9 years of follow-up. Thirty-five and seven metabolites associated with baseline gait speed and grip strength respectively, including six metabolites that associated with both phenotypes. Three metabolites associated with preservation or improvement in gait speed over follow-up, including: sphingomyelin (40:2) (P=2.6×10-4) and behenoyl sphingomyelin (d18:1/22:0) and ergothioneine (both P<0.05). Seven metabolites associated with declines in gait speed, including: 1-carboxyethylphenylalanine (P=8.8×10-5), and N-acetylaspartate, N-formylmethionine, S-adenosylhomocysteine, N-acetylneuraminate, N2,N2-dimethylguanosine, and gamma-glutamylphenylalanine (all P<0.05). Two metabolite modules reflecting sphingolipid and bile acid metabolism associated with physical performance (minimum P=7.6×10-4). These results add to the accumulating evidence suggesting an important role of the human metabolome in physical performance and specifically implicate lipid, nucleotide, and amino acid metabolism in early physical performance decline.

SUBMITTER: Nierenberg JL

PROVIDER: S-EPMC7343486 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study.

Nierenberg Jovia L JL He Jiang J Li Changwei C Gu Xiaoying X Shi Mengyao M Razavi Alexander C AC Mi Xuenan X Li Shengxu S Bazzano Lydia A LA Anderson Amanda H AH He Hua H Chen Wei W Guralnik Jack M JM Kinchen Jason M JM Kelly Tanika N TN

Aging 20200601 12

Age-related declines in physical performance predict cognitive impairment, disability, chronic disease exacerbation, and mortality. We conducted a metabolome-wide association study of physical performance among Bogalusa Heart Study participants. Bonferroni corrected multivariate-adjusted linear regression was employed to examine cross-sectional associations between single metabolites and baseline gait speed (N=1,227) and grip strength (N=1,164). In a sub-sample of participants with repeated asse ...[more]

PMID: 32482911

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Project description:Background and aimsDyslipidemia has been identified as a major risk factor for cardiovascular disease. We aimed to identify metabolites and metabolite modules showing novel association with lipids among Bogalusa Heart Study (BHS) participants using untargeted metabolomics.Methods and resultsUntargeted ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to quantify serum metabolites of 1 243 BHS participants (816 whites and 427 African-Americans). The association of single metabolites with lipids was assessed using multiple linear regression models to adjust for covariables. Weighted correlation network analysis was utilized to identify modules of co-abundant metabolites and examine their covariable adjusted correlations with lipids. All analyses were conducted according to race and using Bonferroni-corrected α-thresholds to determine statistical significance. Thirteen metabolites with known biochemical identities showing novel association achieved Bonferroni-significance, p < 1.04 × 10-5, and showed consistent effect directions in both whites and African-Americans. Twelve were from lipid sub-pathways including fatty acid metabolism (arachidonoylcholine, dihomo-linolenoyl-choline, docosahexaenoylcholine, linoleoylcholine, oleoylcholine, palmitoylcholine, and stearoylcholine), monohydroxy fatty acids (2-hydroxybehenate, 2-hydroxypalmitate, and 2-hydroxystearate), and lysoplasmalogens [1-(1-enyl-oleoyl)-GPE (P-18:1) and 1-(1-enyl-stearoyl)-GPE (P-18:0)]. The gamma-glutamylglutamine, peptide from the gamma-glutamyl amino acid sub-pathway, were also identified. In addition, four metabolite modules achieved Bonferroni-significance, p < 1.39 × 10-3, in both whites and African-Americans. These four modules were largely comprised of metabolites from lipid sub-pathways, with one module comprised of metabolites which were not identified in the single metabolite analyses.ConclusionThe current study identified 13 metabolites and 4 metabolite modules showing novel association with lipids, providing new insights into the physiological mechanisms regulating lipid levels.

Project description:IntroductionEffective connectivity (EC), the causal influence that functional activity in a source brain location exerts over functional activity in a target brain location, has the potential to provide different information about brain network dynamics than functional connectivity (FC), which quantifies activity synchrony between locations. However, head-to-head comparisons between EC and FC from either task-based or resting-state functional MRI (fMRI) data are rare, especially in terms of how they associate with salient aspects of brain health.MethodsIn this study, 100 cognitively-healthy participants in the Bogalusa Heart Study aged 54.2 ± 4.3years completed Stroop task-based fMRI, resting-state fMRI. EC and FC among 24 regions of interest (ROIs) previously identified as involved in Stroop task execution (EC-task and FC-task) and among 33 default mode network ROIs (EC-rest and FC-rest) were calculated from task-based and resting-state fMRI using deep stacking networks and Pearson correlation. The EC and FC measures were thresholded to generate directed and undirected graphs, from which standard graph metrics were calculated. Linear regression models related graph metrics to demographic, cardiometabolic risk factors, and cognitive function measures.ResultsWomen and whites (compared to men and African Americans) had better EC-task metrics, and better EC-task metrics associated with lower blood pressure, white matter hyperintensity volume, and higher vocabulary score (maximum value of p = 0.043). Women had better FC-task metrics, and better FC-task metrics associated with APOE-ε4 3-3 genotype and better hemoglobin-A1c, white matter hyperintensity volume and digit span backwards score (maximum value of p = 0.047). Better EC rest metrics associated with lower age, non-drinker status, and better BMI, white matter hyperintensity volume, logical memory II total score, and word reading score (maximum value of p = 0.044). Women and non-drinkers had better FC-rest metrics (value of p = 0.004).DiscussionIn a diverse, cognitively healthy, middle-aged community sample, EC and FC based graph metrics from task-based fMRI data, and EC based graph metrics from resting-state fMRI data, were associated with recognized indicators of brain health in differing ways. Future studies of brain health should consider taking both task-based and resting-state fMRI scans and measuring both EC and FC analyses to get a more complete picture of functional networks relevant to brain health.

Project description:Sarcopenia and obesity have been independently associated with physical function decline, however little information is currently available on the relationship between sarcopenic obesity and physical performance, mainly in middle aged women. The present study aims to estimate the prevalence of sarcopenic obesity and to explore the relationship between sarcopenic obesity and physical performance in middle-aged women from Northeast Brazil.A cross-sectional study of women (40-65 years) living in Parnamirim, a city in Northeast Brazil (n = 491). Physical performance was assessed by grip strength, knee extensor and flexor strength (isometric dynamometry), gait speed, and chair stands. Using bioelectrical impedance analysis (BIA), appendicular skeletal muscle mass divided by height squared (kg / m(2)) was used to define sarcopenia. Waist circumference ≥ 88 cm was defined as abdominal obesity. Sarcopenic obesity was defined as the coexistence of obesity and sarcopenia. The physical performance outcomes were regressed in four groups defined by combinations of sarcopenia and obesity, adjusting for potential confounders (age, education and menopausal status).Prevalence rates of the four obesity-sarcopenia groups were: Sarcopenic obesity (7.1 %), obesity (67.4 %), sarcopenia (12.4 %) and normal (13 %). Women with sarcopenic obesity had significantly lower grip strength, weaker knee extension and flexion and longer time to raise from a chair compared with non-obese and non-sarcopenic women (p.values < 0.001). Except for the chair stands, these statistically significant differences were also found between sarcopenic obese and obese women. There was no significant difference for gait speed across the four groups (p = 0.50).Sarcopenic obesity was present in 7 % of this population of middle-aged women from Northeast Brazil and it was associated with poor physical performance. Sarcopenic obesity may occur in middle-aged women with performance limitations beyond pure sarcopenia-related muscle mass or obesity alone.

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Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study.

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Serum metabolites associate with physical performance among middle-aged adults: Evidence from the Bogalusa Heart Study.

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