Unraveling the protein-metabolite network of sarcopenia in plasma: A large-scale Mendelian randomization study

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Archives of gerontology and geriatrics Pub Date : 2025-02-17 DOI:10.1016/j.archger.2025.105788

Wenhang Zuo, Jin Peng, Wen Guo, Jinhui Wu

{"title":"Unraveling the protein-metabolite network of sarcopenia in plasma: A large-scale Mendelian randomization study","authors":"Wenhang Zuo, Jin Peng, Wen Guo, Jinhui Wu","doi":"10.1016/j.archger.2025.105788","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Some plasma molecules may have an effect on sarcopenia, but it is not fully understood. We aimed to comprehensively explore the causal effects of plasma proteins and metabolites on sarcopenia traits, and to unravel their network.</div></div><div><h3>Methods</h3><div>A two-sample Mendelian randomization design was adopted. The levels of 4,907 plasma proteins from 35,559 Icelanders, and 1,400 plasma metabolites from 8,299 Europeans, were set as exposures. Low handgrip strength, appendicular lean mass, and usual walking pace from Europeans were set as outcomes. Inverse-variance weighted (IVW) and four other methods, along with sensitivity analyzes, were performed to estimate the causal effects. Enrichment and pathway analyzes were conducted to present their characteristics. IVW was used to estimate the bidirectional relationships between sarcopenia-related proteins and metabolites, and to visualize them within a network.</div></div><div><h3>Results</h3><div>We identified 76 relationships between proteins and sarcopenia traits. The absolute values of causal effects (β<sub>IVW</sub>) ranging from 0.01 to 0.35. IL2, AIF1, GDNF, CXCL13, LRRTM3, and SLPI were the top six proteins ranked by causal effects. Additionally, 22 relationships between metabolites and sarcopenia traits were identified, with absolute values of β<sub>IVW</sub> ranging from 0.02 to 0.22. Sulfate and serine/pyruvate ratio had the highest values. The network diagram showed some key nodes, such as ISOC1, GSTA1, tryptophan and 5α-androstan-3α,17β-diol monosulfate.</div></div><div><h3>Conclusions</h3><div>This work unraveled a molecular network of sarcopenia in plasma for the first time and identified some key proteins and metabolites. It may help to understand the mechanisms of sarcopenia, providing new insights for predicting, diagnosing and treating sarcopenia.</div></div>","PeriodicalId":8306,"journal":{"name":"Archives of gerontology and geriatrics","volume":"132 ","pages":"Article 105788"},"PeriodicalIF":3.5000,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of gerontology and geriatrics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167494325000469","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Some plasma molecules may have an effect on sarcopenia, but it is not fully understood. We aimed to comprehensively explore the causal effects of plasma proteins and metabolites on sarcopenia traits, and to unravel their network.

Methods

A two-sample Mendelian randomization design was adopted. The levels of 4,907 plasma proteins from 35,559 Icelanders, and 1,400 plasma metabolites from 8,299 Europeans, were set as exposures. Low handgrip strength, appendicular lean mass, and usual walking pace from Europeans were set as outcomes. Inverse-variance weighted (IVW) and four other methods, along with sensitivity analyzes, were performed to estimate the causal effects. Enrichment and pathway analyzes were conducted to present their characteristics. IVW was used to estimate the bidirectional relationships between sarcopenia-related proteins and metabolites, and to visualize them within a network.

Results

We identified 76 relationships between proteins and sarcopenia traits. The absolute values of causal effects (β_IVW) ranging from 0.01 to 0.35. IL2, AIF1, GDNF, CXCL13, LRRTM3, and SLPI were the top six proteins ranked by causal effects. Additionally, 22 relationships between metabolites and sarcopenia traits were identified, with absolute values of β_IVW ranging from 0.02 to 0.22. Sulfate and serine/pyruvate ratio had the highest values. The network diagram showed some key nodes, such as ISOC1, GSTA1, tryptophan and 5α-androstan-3α,17β-diol monosulfate.

Conclusions

This work unraveled a molecular network of sarcopenia in plasma for the first time and identified some key proteins and metabolites. It may help to understand the mechanisms of sarcopenia, providing new insights for predicting, diagnosing and treating sarcopenia.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Archives of gerontology and geriatrics 医学-老年医学

CiteScore

7.30

自引率

5.00%

发文量

198

审稿时长

16 days

期刊介绍： Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.