Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases

Zonghao Qian; Yuzhen Huang; Yucong Zhang; Ni Yang; Ziwei Fang; Cuntai Zhang; Le Zhang

doi:10.3389/fgene.2024.1353908

Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases

Front Genet. 2024 Feb 13:15:1353908. doi: 10.3389/fgene.2024.1353908. eCollection 2024.

Authors

Zonghao Qian^#^{1

2}, Yuzhen Huang^#^{1

2}, Yucong Zhang^{1

2}, Ni Yang^{1

2}, Ziwei Fang^{1

2}, Cuntai Zhang^{1

2}, Le Zhang^{1

2}

Affiliations

¹ Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

^# Contributed equally.

Abstract

Background: Physical weakness and cardiovascular risk increase significantly with age, but the underlying biological mechanisms remain largely unknown. This study aims to reveal the causal effect of circulating metabolites on frailty, sarcopenia and vascular aging related traits and diseases through a two-sample Mendelian Randomization (MR) analysis. Methods: Exposures were 486 metabolites analyzed in a genome-wide association study (GWAS), while outcomes included frailty, sarcopenia, arterial stiffness, atherosclerosis, peripheral vascular disease (PAD) and aortic aneurysm. Primary causal estimates were calculated using the inverse-variance weighted (IVW) method. Methods including MR Egger, weighted median, Q-test, and leave-one-out analysis were used for the sensitive analysis. Results: A total of 125 suggestive causative associations between metabolites and outcomes were identified. Seven strong causal links were ultimately identified between six metabolites (kynurenine, pentadecanoate (15:0), 1-arachidonoylglycerophosphocholine, androsterone sulfate, glycine and mannose) and three diseases (sarcopenia, PAD and atherosclerosis). Besides, metabolic pathway analysis identified 13 significant metabolic pathways in 6 age-related diseases. Furthermore, the metabolite-gene interaction networks were constructed. Conclusion: Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.

Keywords: frailty; human blood metabolites; mendelian randomization; sarcopenia; vascular aging.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Key Research and Development Program of China (2020YFC2008000) and the Key Research and Development Program of Hubei Province (2022BCA001) to Cuntai Zhang; the National Key Research and Development Program of China (2023YFC3605100), the Hubei Provincial Natural Science Foundation of China (2023AFB685) and the National Natural Science Foundation of China (81873533) to LZ.