ArticleScientific reports2026
Exercise training mitigates age-related cognitive decline by attenuating TMAO-induced inflammation.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Exercise-Mediated Modulation of the NLRP3 Inflammasome in Aging and Neurodegenerative Diseases: Mechanisms, Microglial Crosstalk, and Translational Perspectives.Molecular neurobiology · 2026Review
- GW9508-Induced Activation of GPR40 in Thymic Epithelial Cells: A Therapeutic Strategy to Delay Thymic Aging.Aging cell · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The metabolites produced by the gut microbiota play a role in age-related cognitive decline through the gut-brain axis. Within this axis, trimethylamine N-oxide (TMAO) permeates the intestinal epithelial barrier and enters systemic circulation, triggering inflammation in the central nervous system and ultimately leading to cognitive decline. However, it remains unclear whether exercise training's specific mechanism for delaying age-related cognitive decline is associated with TMAO regulation and inhibition of neuroinflammation. The aging rat model was established by intraperitoneal injection of D-galactose in SD rats, while simultaneous exercise training and TMAO interventions were conducted. The effects of exercise on cognitive function were evaluated using the new object recognition (NOR) test, the Morris water maze (MWM) test, and the radial arm maze (RAM) test. Additionally, the expression levels of TMAO and NLRP3 inflammasome-related proteins in aging rats were measured using enzyme-linked immunosorbent assays (ELISA) and Western blotting (WB), respectively. A D-galactose-induced senescence model was established in HT22 cells. Following TMAO/DMB intervention, SPiDER-β-galactosidase (SPiDER-β-gal)-positive cells and NLRP3 inflammasome-related proteins were analyzed. To validate the regulatory role of TXNIP in TMAO-induced senescence-inflammation phenotypes, knockdown/overexpression experiments were conducted. Trx1-C32S mutant cells were utilized to verify that TMAO enhances the disulfide bond binding affinity between TXNIP and Trx1. Exercise training effectively delayed the cognitive dysfunction induced by D-galactose in aging rats, as evidenced by a 22.6% increase in the discrimination index in the NOR test, an 11.2% prolongation of time in the target quadrant and a 50% enhancement in the number of platform crossings in the MWM test, and a 41.8% improvement in working memory in the RAM test. This neuroprotective effect is potentially mediated through the inhibition of the intestinal metabolite TMAO (with plasma TMAO levels reduced by 40.3%) and subsequent modulation of the TXNIP-NLRP3-Caspase-1-GSDMD inflammatory pathway. The cellular experiments revealed that TMAO/DMB intervention modulates cellular senescence-inflammation phenotypes, with TXNIP acting as a positive regulator of the NLRP3 pathway. TMAO enhances TXNIP-mediated inhibition of the redox system by promoting disulfide bond formation at Trx1-C32, providing cellular-level evidence for the underlying mechanism.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.