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Targeting FABP4 Improves Healthy Aging by Rejuvenating Liver Metabolism

ABSTRACT: Aging is characterized by progressive metabolic dyshomeostasis that increases morbidity and mortality. It remains underexplored whether metabolic aging is a targetable process to improve healthy aging. Here, we performed a proteomic analysis in a cohort of young and elderly adults. Among 9 aging-sensitive proteins shared by both female and male, fatty acid binding protein 4 (FABP4) was identified as a reliable biomarker that was consistently upregulated in aged mice. Silencing FABP4 in the elderly mice by adeno-associated virus significantly rejuvenated metabolic activity, and improved glucose intolerance and steatosis. Transcriptome analysis revealed a restoration of the pro-aging gene reprogramming towards inflammation and metabolic disorders in the liver after FABP4 knockdown. Specifically, FABP4 knockdown promoted degradation of cholesterol and fatty acids, while repressing gluconeogenesis. Furthermore, administration of an FABP4 inhibitor BMS309403 delivered similar metabolic benefits in the elderly mice. Thus, FABP4 is a practicable target to improve metabolic aging in the elderly.

ORGANISM(S): Mus musculus

PROVIDER: GSE215378 | GEO | 2025/10/13

REPOSITORIES: GEO

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Targeting FABP4 Improves Healthy Aging by Rejuvenating Liver Metabolism

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