Metabolomics analysis of human plasma metabolites reveals the age- and sex-specific associations

Abstract

Objectives: The objective of this study was the investigation of age- and sex-associations in a set of blood plasma metabolites in healthy male and female subjects.

Methods: A comparison study design with male and female subjects of various ages was used. Metabolic profiling was performed using electrospray ionization tandem mass spectrometry that yielded 186 metabolite concentrations for each study participant. The key age-related metabolites were identified using an integrative analysis of absolute concentrations, metabolite ratios and the differential correlation of pairwise metabolite concentrations. All of the age-associated metabolites were adjusted prior to the analysis to account for differences in Body Mass Index (BMI).

Results: A total of 236 plasma samples from 140 female and 96 male subjects aged 20 to 82 years-old were collected and analyzed in the study. 13 and 14 age-associated metabolites (|r| > 0.33 and p < 6.6×10⁻⁵), 438 and 337 age-associated metabolite ratios (|r| > 0.37 and p < 3.5×10⁻⁶), and 5 and 10 core metabolites were discovered in the female and male groups, respectively. 80% of the metabolites displaying associations with age belonged to sphingolipids and phosphatidylcholines, and the two sexes shared less than 50% of the age-associated metabolites.

Conclusion: The study found that changes in metabolite concentrations, metabolite ratios and differential correlations were age and sex-specific.

Graphical Abstract

Keywords:

• Ageing
• differential correlation network
• metabolic biomarker
• metabolomics
• sex
• metabolite ratios

Ethical approval

This study received ethical approval from Health Research Ethics Authority of the Faculty of Medicine of Memorial University, St. John’s, Newfoundland, Canada. Written informed consent was obtained from all volunteers.

Author contributions

WDZ: conceptualized and designed the study, oversaw the sample collection, data analyses, and contributed to the drafting of the final manuscript; YXW, GSW and TH contributed to data analyses and critical comments on the final manuscript; SL and ED contributed to the metabolic profiling, data analyses and critical comments on the final manuscript; GS contributed to the data collection and critical comments on the final manuscript；RNJ, GHJ and TMY contributed to the data analyses and critical comments on the final manuscript. All authors approved the final manuscript as submitted.

Acknowledgments

We thank all the study participants who made this study possible, and all the staff in the hospital operation theaters who helped us in collecting samples.

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

The present work was financially supported by Science and Technology Development Plan of Jilin Province [20180101302JC], Youth Technology Backbone Training Program of Health Department of Jilin Province [2017Q020], Bethune Project of Jilin University [2018A08], Education Department of Jilin Province [JJKH20190107KJ].