ReviewFrontiers in physiology2026
The lactate shuttle in ageing: a metabolic bridge between muscle fatigue and brain resilience.
Review in Frontiers in physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Traditionally, lactate was considered a glycolytic byproduct that causes muscle fatigue, but now its biological role is undergoing a significant paradigm shift. Emerging evidence suggests that lactate acts as an inter-organ metabolic and signaling mediator linking exercise-induced peripheral metabolic stress to central nervous system adaptation. This review explores how exercise drives lactate pulses and delivers them to the brain through the circulatory system and blood-brain barrier (BBB). Lactate has a dual function in the brain, serving not only as the preferred energy substrate for active neurons but also as a core signaling molecule. Through pathways involving G protein coupled receptor 81 (GPR81) and histone lactylation, lactate regulates neuroplasticity, cerebrovascular function, neuroinflammation, and antioxidant defense, thereby establishing cognitive resilience. During aging, multiple components of this proposed lactate signaling axis may become compromised, including skeletal muscle lactate production, circulatory and blood-brain barrier transport, and cellular responsiveness within the brain. Such multi-level impairment may contribute to neuromuscular co-aging and may increase vulnerability to neurodegenerative disorders, including Alzheimer's disease. Ultimately, we explored the translational potential of restoring the lactate signaling axis through multimodal strategies to promote healthy aging, including precise exercise prescriptions, GPR81 targeted therapy, metabolic interventions, and biomarker development. This review aims to combine metabolic science with evidence of neuroaging, providing a new theoretical framework for determining the primacy of exercise-driven brain health and advancing anti-aging interventions.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.