Causal relationship between gut microbiota and ageing: A multi-omics Mendelian randomization study

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Archives of gerontology and geriatrics Pub Date : 2025-01-20 DOI:10.1016/j.archger.2025.105765

Guolin Zhang , Yuqing Lu , Zhen Wang , Ruicong Ma , Hongjin Jin , Jingsi Zhang , Fengyi Liu , Yanchun Ding

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引用次数: 0

Abstract

Introduction

Observational studies and clinical trials have suggested a connection between gut microbiota and aging. However, the causal relationship between them remains undetermined.

Objectives

This study aimed to use bidirectional two-sample Mendelian randomization (TSMR) analysis to explore the causal relationship between gut microbiota and aging.

Methods

Summary statistics from genome-wide association studies (GWAS) on gut microbiota and seven aging-related phenotypes were employed for TSMR analysis. Reverse Mendelian randomization (MR) analysis was performed to assess the potential for reverse causality. Additionally, the relationship between Akkermansia muciniphila and inflammation-related proteins and metabolites was further investigated. The effects of Akkermansia muciniphila on aging were also examined in Caenorhabditis elegans by measuring both lifespan and healthspan.

Results

MR analysis of 207 microbial taxa and seven aging phenotypes revealed 44 causal relationships between the gut microbiota and aging. Akkermansia muciniphila was found to be causally linked to several aging-related traits, including mvAge, appendicular lean mass, and grip strength (P < 0.05). Reverse MR analysis identified 23 causal relationships, but no bidirectional causality was observed. Moreover, Akkermansia muciniphila is causally related to ST1A1, taurine bile acid, and mannose (P < 0.05). In Caenorhabditis elegans, treatment with Akkermansia muciniphila significantly extended lifespan (P < 0.05) and improved mobility in aging nematodes.

Conclusion

TSMR analysis uncovers multiple potential causal links between gut microbiota and aging, particularly Akkermansia muciniphila. Experimental results support its role in alleviating aging. This study provides a strong foundation for future research on gut microbiota's role in aging.

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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.