Senotherapeutic potential of Mediterranean diet-derived bioactives in healthy aging and frailty

Abstract

Population aging is accompanied by an increasing burden of frailty, sarcopenia, metabolic dysfunction, neurodegeneration, and other age-related conditions. Growing evidence suggests that nutrition may influence biological aging through pathways related to cellular senescence, chronic low-grade inflammation, oxidative stress, mitochondrial function, and gut microbiota composition. The Mediterranean diet is one of the most extensively studied dietary patterns for healthy aging and provides a complex matrix of plant foods, extra-virgin olive oil, fiber, unsaturated fatty acids, and diverse bioactive compounds. This review discusses the potential relevance of Mediterranean diet-derived bioactives to senescence-related mechanisms and frailty-related outcomes. Mechanistic links involving inflammatory signaling, redox balance, nutrient-sensing pathways, mitochondrial homeostasis, gut microbiota-mediated immune regulation, and functional decline are considered. Although preclinical evidence supports the biological plausibility of these effects, human evidence remains heterogeneous, and direct clinical proof of senolytic or senomorphic activity from habitual Mediterranean diet exposure is still limited. Therefore, Mediterranean diet-derived bioactives should be interpreted as components of a multi-target nutritional strategy rather than as isolated anti-aging agents. Future studies should integrate dietary assessment, biomarkers of cellular senescence, microbiome and metabolome profiling, inflammatory markers, and standardized functional outcomes to clarify whether Mediterranean diet-based approaches can delay frailty and promote healthy longevity through senescence-related mechanisms.

Keywords: Mediterranean diet, senotherapeutics, healthy aging, inflammaging, frailty