Front Aging Neurosci. 2025 Nov 19;17:1676926. doi: 10.3389/fnagi.2025.1676926. eCollection 2025.

ABSTRACT

INTRODUCTION: Cognitive decline advances with age, increasing the risk of dementia and Alzheimer’s disease among older adults. Medium-chain triglyceride (MCT) ketogenic diets have shown potential in slowing down age-related cognitive decline; however, the exact neuroprotective roles of MCT components, specifically decanoic acid and octanoic acid, remain unclear.

METHODS: Swiss Albino mice were subjected to D-galactose to trigger accelerated aging, or to a combination of D-galactose and aluminium chloride to mimic Alzheimer’s disease-like neurotoxicity. The animals received treated with decanoic acid, octanoic acid, or both. Cognitive function was assessed using the Morris water maze, while brain tissues were examined for oxidative stress markers, autophagy indicators, senescence activity, and amyloid-β levels.

RESULTS: Decanoic acid significantly improved learning and memory performance, enhanced antioxidant enzyme activity (superoxide dismutase, reduced glutathione, catalase), promoted autophagy by inhibiting mTOR, reduced cellular senescence (β-galactosidase-positive cells), and decreased amyloid-β toxicity. In contrast, octanoic acid showed no significant mechanistic effects, though it slightly improved cognitive behaviour.

DISCUSSION: This study demonstrates that decanoic acid, unlike octanoic acid, exhibits significant neuroprotective effects against accelerated aging and neurotoxicity, similar to Alzheimer’s disease. These findings highlight the differences in the neuroprotective mechanisms of decanoic and octanoic acids, implying that MCT-based diets should be re-evaluated as a preventive strategy for cognitive decline and neurodegenerative diseases.

PMID:41346437 | PMC:PMC12672871 | DOI:10.3389/fnagi.2025.1676926

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