Metabolic Clues to Aging: Exploring the Role of Circulating Metabolites in Frailty, Sarcopenia and Vascular Aging Related Traits and Diseases

Overview

Journal Front Genet

Date 2024 Feb 28

PMID 38415056

Authors

Zonghao Qian

Yuzhen Huang

Yucong Zhang

Ni Yang

Ziwei Fang

Cuntai Zhang

Le Zhang

Affiliations

Soon will be listed here.

Abstract

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. 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. 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. Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.

Citing Articles

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