Dietary geroprotective peptides: structural determinants, AI-driven discovery, and synthetic biology production for...

Ageing is characterised by progressive physiological decline, driving global interest in interventions that target its fundamental mechanisms. Dietary bioactive peptides are emerging as a promising class of natural geroprotectors, yet a consolidated understanding of their structure-activity relationships and the advanced technologies enabling their discovery and production is needed. This review consolidates recent advances concerning food-derived geroprotective peptides. We systematically evaluate their dietary sources, structural characteristics governing bioactivity, and multi-mechanistic actions against core ageing hallmarks. Furthermore, we explore the transformative potential of food synthetic biology for sustainable production and artificial intelligence (AI) for the accelerated discovery of these peptides. Evidence demonstrates that peptides sourced from plants, animals, and marine organisms can extend healthspan and lifespan in model systems. Their bioactivity is governed by key structural determinants such as low molecular weight and specific amino acid sequences, which promote bioavailability and enable targeted modulation of conserved longevity networks, including Nrf2, IIS, and mTOR signalling. A significant mechanism of action involves the beneficial remodelling of gut microbiota, which mediates systemic improvements in metabolic, inflammatory, and cognitive health. Critically, AI-driven platforms are now overcoming traditional discovery barriers, while engineered microbial biosystems offer a viable route for scaled-up synthesis of these peptides. In conclusion, food-derived peptides represent compelling candidates for development into functional foods and nutraceuticals. Harnessing these peptides through modern technologies offers a strategic, mechanism-based approach to promote healthspan and redefine the role of nutrition in healthy ageing.