AUTHOR=Jain Shreshta , Vohora Divya 

TITLE=Decanoic acid, an MCT dietary component, alleviates cognitive impairment, cellular senescence, and promotes autophagy in accelerated aging and neurotoxic mouse models induced by chronic administration of D-galactose and D-galactose/AlCl3

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 17 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1676926

DOI=10.3389/fnagi.2025.1676926

ISSN=1663-4365

ABSTRACT=IntroductionCognitive 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.MethodsSwiss 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.ResultsDecanoic 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.DiscussionThis 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.