Hormesis and health: molecular mechanisms and the key role of polyphenols

Hormesis is a fundamental adaptive mechanism in response to moderate stress stimuli. This phenomenon underlies many preventive and therapeutic strategies, particularly in the context of chronic-degenerative diseases. The aim of the current article is to analyze the main molecular pathways involved in hormetic processes, and their roles in promoting longevity, cellular resilience, and protection against harmful agents. Among the substances capable of triggering hormetic responses, polyphenols, bioactive compounds found in many plant-based foods, play a prominent role. Although polyphenols have relatively modest direct antioxidant activity, they are powerful inducers of hormetic responses. They act as low-dose xenobiotics, capable of stimulating endogenous cellular defense mechanisms. This dual nature, potentially toxic at high doses but beneficial at low concentrations, grants polyphenols a central role in modulating oxidative stress and inflammation. This review offers a novel perspective by integrating molecular, nutritional, and systemic dimensions of polyphenol-induced hormesis, with particular emphasis on the dynamic crosstalk between cellular stress responses and microbiota-derived signals. This manuscript highlights underappreciated mechanisms and proposes a more interconnected framework for understanding the health effects of polyphenols. In conclusion, polyphenol-induced hormesis appears as an innovative and promising paradigm for health promotion and the prevention of age-related diseases.