Therapeutic potential of chlorogenic acid in age-associated metabolic and neurodegenerative disorders

Abstract Chlorogenic acid (CGA), a polyphenolic compound abundant in coffee and various plants, exhibits broad therapeutic potential in age-related metabolic and neurodegenerative disorders. CGA exerts potent antioxidant, anti-inflammatory, and metabolic regulatory effects by modulating key signaling pathways such as AMPK, SIRT1, mTOR, FOXO, and Nrf2. Preclinical studies demonstrate its ability to mitigate oxidative stress, regulate autophagy, improve lipid and glucose metabolism, and protect against neurodegeneration. Moreover, CGA enhances mitochondrial function and preserves cellular homeostasis. However, emerging evidence suggests that under conditions of low folate or B-vitamin availability, CGA may increase plasma homocysteine levels, raising concerns about its effects on methylation and vascular health. This review provides a comprehensive analysis of CGA’s molecular targets and mechanisms of action, with particular emphasis on its implications in redox regulation, autophagy, metabolic homeostasis, and neurodegeneration. Collectively, current evidence positions CGA as a promising nutraceutical candidate for integrative strategies aimed at preventing or mitigating chronic degenerative diseases and promoting healthy aging.