Synergistic Natural Products in Anti-Ageing: Mechanistic Insights, Experimental Evidence, and Translational Perspectives

Ageing is characterised by a progressive decline in physiological function driven by oxidative stress, chronic inflammation, and metabolic imbalance. Natural products contain diverse bioactive compounds capable of regulating these interconnected processes through convergent molecular pathways. This review synthesises current evidence across six major classes of natural bioactives, including polyphenols, terpenoids, polyamines, polysaccharides, fatty acids, and bioactive peptides, and examines their roles within metabolic, redox, inflammatory, and epigenetic networks. Individually, these compounds enhance mitochondrial function, modulate AMP-activated protein kinase (AMPK)–sirtuin 1 (SIRT1)–mechanistic target of rapamycin complex 1 (mTORC1) signalling, activate the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) antioxidant pathway, suppress nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation, and improve cellular stress resilience. When used in combination, they exhibit synergistic interactions that amplify antioxidant, anti-inflammatory, and metabolic benefits, resulting in measurable improvements in lifespan and healthspan. Quantitative analyses demonstrate that rationally designed combinations achieve approximately 20–35 percent greater efficacy than single agents, reflecting coordinated multi-target reinforcement rather than simple additive effects. Overall, these insights highlight the mechanistic rationale, experimental evidence, and translational potential of synergistic natural bioactives as promising strategies for promoting healthy ageing and mitigating age-related decline.