Age, Sex, Body Mass Index, Diet and Menopause Related Metabolites in a Large Homogeneous Alpine Cohort

Abstract

Metabolomics in human serum samples provide a snapshot of the current metabolic state of an individuum. Metabolite concentrations are influenced by both genetic and environmental factors. Concentrations of certain metabolites can further depend on age, sex, menopause, and diet of study participants. A better understanding of these relationships is pivotal for the planning of metabolomics studies involving human subjects and interpretation of their results. We generated one of the largest single-site targeted metabolomics data sets consisting of 175 quantified metabolites in 6872 study participants. We identified metabolites significantly associated with age, sex, body mass index, diet, and menopausal status. While most of our results agree with previous large-scale studies, we also found novel associations including serotonin as a sex and BMI-related metabolite and sarcosine and C2 carnitine showing significantly higher concentrations in post-menopausal women. Finally, we observed strong associations between higher consumption of food items and certain metabolites, mostly phosphatidylcholines and lysophosphatidylcholines. Most, and the strongest, relationships were found for habitual meat intake while no significant relationships were found for most fruits, vegetables, and grain products. Summarizing, our results reconfirm findings from previous population-based studies on an independent cohort. Together, these findings will ultimately enable the consolidation of sets of metabolites which are related to age, sex, BMI, and menopause as well as to participants’ diet.

Sex-specificity of the C. elegans metabolome

“…UHPLC-HRMS data were analyzed using Metaboseek software after file conversion to the mzXML format via MSConvert (v3.0, ProteoWizard) 1,2 . A total of 41,795 features were detected in ESI-and 68,389 features in ESI + .…”

“…Recent studies of metabolism and related physiological responses in humans and rodent models have revealed dramatic differences between sexes [1][2][3][4][5] . For example, targeted metabolomic analysis of human serum revealed significant differences for one-third of annotated metabolites 6 .…”

The metabolomics of human aging: Advances, challenges, and opportunities

“…Since then, several dozen such studies have been published with a variety of populations, age ranges, sample types, study designs, and underlying metabolomics technologies ( Fig. 1 and Table 1 ) ( 24 – 59 ). The number of participants has reached the thousands in several studies [including two studies with 20,000 or more participants ( 34 , 48 )], a feat that has become more common with the presence of ongoing, population-scale cohorts with biobanked samples and commercially available platforms for standardized metabolite quantification.…”

“…In human metabolomics cohorts, methionine itself has been associated with age repeatedly, including in plasma ( 40 , 43 ), serum ( 37 ), and CSF ( 53 ). A decrease in arginine and an increase in ornithine was also observed in serum, both of which can feed into the polyamine synthesis pathway ( 41 ), and several ratios between serum levels of ornithine, arginine, putrescine, and spermidine were associated with age ( 59 ). Glutathione was observed to be associated with age ( 39 , 52 , 55 ), which might indicate aging-related changes involving the transsulfuration pathway.…”

Whole Exome Sequencing Enhanced Imputation Identifies 85 Metabolite Associations in the Alpine CHRIS Cohort

“…Measurement, data normalization and quality assessment of the targeted metabolomics data are described in [ 49 ]. In brief, the AbsoluteIDQ p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) was used to determine absolute concentrations for 188 metabolites in serum samples from participants of the CHRIS study.…”