Mediterranean Diet and Exercise in Healthy Aging: A Hormetic Framework for Molecular Convergence, Mitochondrial Resilience, and the Antioxidant Paradox

Healthy aging depends on preserving the capacity to adapt to physiological stress. Physical exercise is a prototypical hormetic stimulus that transiently perturbs redox, energetic, mechanical, and inflammatory homeostasis, activating pathways involved in mitochondrial remodeling, metabolic flexibility, cellular repair, and stress resistance. The Mediterranean diet may shape the context in which these responses occur through polyphenols, unsaturated fatty acids, fermentable fibers, micronutrients, and microbiota-derived metabolites. This review develops a hormetic framework for the molecular convergence between Mediterranean dietary exposure and exercise in healthy aging while distinguishing mechanistic plausibility from demonstrated biological interaction. Particular attention is given to Nrf2–Keap1, AMPK–SIRT1–PGC-1α, mTOR–autophagy, NF-κB/NLRP3, and eNOS/NO networks, with mitochondrial quality control considered a candidate integrative hub. The gut–muscle–mitochondria axis and microbial polyphenol metabotypes are discussed as potential contributors to interindividual variability. The antioxidant paradox is framed through a proposed adaptive redox window in which physiological stress and nutritional modulation support adaptation without exceeding or suppressing compensatory capacity. Current human evidence supports molecular convergence and biological complementarity more strongly than formally demonstrated diet × exercise interaction, while evidence of true synergy remains particularly limited; the framework is therefore hypothesis-generating and requires factorial and mechanistic testing in older adults.