A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice.

Overview

1. Dongguan Key Laboratory of Public Health Laboratory Science, the First Dongguan Affiliated Hospital, School of Public Health Guangdong Medical University Dongguan China
2. Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, School of Medical Technology Guangdong Medical University Dongguan China
3. Fogang County People's Hospital Qingyuan Guangdong China
4. Dongguan Key Laboratory of Sepsis Translational Medicine, the First Dongguan Affiliated Hospital Guangdong Medical University Dongguan China

Abstract

Aging disrupts systemic metabolism, but the mechanisms by which gut microbial metabolites drive tissue‐specific decline remain unclear. We conducted a multi‐organ, multi‐omics atlas across the gut, serum, liver, lung, and cortex in young and early‐aged mice to address this. We identified a conserved aging signature marked by the microbiota‐associated depletion of protective circulating metabolites, such as lysophosphatidylcholines (LPCs), concurrently with the systemic accumulation of pro‐oxidative microbial catabolites, specifically trimethylamine N‐oxide (TMAO) and indole‐3‐acetic acid (IAA). This microbial‐metabolic drift disrupted systemic lipid transport and redox balance, leading to distinct organ‐level vulnerabilities: hepatic lipid retention and ferroptosis susceptibility, pulmonary immune‐redox activation, and cortical neurochemical dysregulation. To establish functional relevance, we conducted an integrated meta‐analysis of 40 independent studies encompassing natural aging models, fecal microbiota transplantation (FMT), and probiotic interventions. This quantitative synthesis provided convergent evidence that microbial remodeling is a functionally relevant correlate associated with systemic aging phenotypes by restoring intestinal barrier integrity (upregulating ZO‐1, MUC2), suppressing tissue inflammatory factors (IL‐6, IL‐1β, TNF‐α), and mitigating oxidative stress (reducing MDA and restoring SOD/GSH). Together, our findings highlight gut‐derived metabolic reprogramming as a modifiable, upstream driver of systemic aging, offering tractable targets for therapeutic intervention.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• doi:10.17632/9ys25jktgw.2, at the source; found in “Data Availability Statement”

Data Availability Statement

The raw metabolomics and meta‐analysis datasets generated and analyzed in this study are publicly available in the Mendeley Data repository at https://data.mendeley.com with the identifier DOI: 10.17632/9ys25jktgw.2 (https://doi.org/10.17632/9ys25jktgw.2). All additional data supporting the findings of this study are available within the article and its Supporting Information files.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 8 MeSH terms, 3 funders, 43 references.

Cite

This paper

Sajid, S., Huang, J., Kong, S., Lai, C., Tan, Z., Shao, Y., & Guo, L. (2026). A Multi-Organ Atlas Links Gut Microbial Metabolites to Systemic Redox Changes in Aging Mice. Aging cell, 25(3), e70433. https://doi.org/10.1111/acel.70433

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