Dual cognitive and motor training improves cognitive function in aging rats
The combined regimen lowered TMAO accumulation and suppressed inflammatory signaling more effectively than cognitive training alone.
Molecular neurobiology · Zhang R et al. · Paper published 28 Sep 2026
In 18-month-old male Sprague-Dawley rats with D-galactose-induced aging, researchers tested whether combining cognitive and motor training outperforms cognitive training alone. The team divided thirty rats into five groups, using novel object recognition and Morris water maze tests to evaluate cognitive function. They also examined hippocampal tissue and cultured HT22 cells to trace inflammatory pathways. Cognitive training alone alleviated cognitive deficits and reduced hippocampal TXNIP and NLRP3 expression. However, cognitive-motor dual-task training produced greater cognitive gains while also curbing TMAO accumulation and TXNIP overexpression. Cell experiments confirmed that TMAO worsened senescence and inflammation through the TXNIP-NLRP3 cascade, while inhibiting TXNIP reversed this damage. TMAO also increased NLRP3 binding to ASC. Overall, the dual-task regimen showed superior protective efficacy against age-related cognitive decline.
Why it matters
The findings highlight how combining physical and mental exercises may protect the aging brain by simultaneously targeting systemic metabolites and downstream neuroinflammatory cascades.
Caveats
The study relied on a small sample of thirty male rodents subjected to chemically accelerated aging, meaning these findings cannot yet be generalized to naturally aging humans.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Cognitive-Motor Dual Task Training Synergistically Improves Aging-related Cognitive Dysfunction By Reducing TMAO and Suppressing TXNIP/NLRP3 Pathway
Zhang R, Dai T, Zhu Z et al.
Molecular neurobiology · 28 Sep 2026 · Peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Animals
- Status
- Peer-reviewed
More on Brain aging
See allHuman neurons accumulate far more mutations over lifespan than shorter-lived mammals
Cortical neurons gain mutations at similar yearly rates across six species, leaving aged humans with uniquely high mutational burdens and transcriptomic dysregulation.
bioRxiv : the preprint server for biology · Caglayan E et al.
CAR T cells targeting inflammatory bone marrow progenitors restore cognition in aged mice
Clearing these peripheral myeloid cells remodeled brain macrophages and improved cognitive performance without requiring the engineered immune cells to enter the brain.
bioRxiv · Harris AS et al.
Extracellular cGAMP drives neuroinflammation and premature aging phenotypes in mice
Loss of the cGAMP-degrading enzyme ENPP1 allows microglia-derived signaling molecules to trigger STING-dependent inflammation across multiple brain cell types.
bioRxiv · R. Carvalho D et al.
Directly converted human neuronal spheroids preserve donor age and model Alzheimer disease
The three-dimensional cell platform maintains biological aging markers while spontaneously developing hallmark pathologies of sporadic Alzheimer disease.
bioRxiv · Alsolami S et al.
Auditory nerve myelin degeneration defines a subtype of age-related hearing loss
Researchers linked poor auditory nerve synchrony and myelin degradation to amplified communication difficulties in older humans, beyond standard hearing thresholds.
medRxiv : the preprint server for health sciences · Harris KC et al.