Mediterranean diet and inflammaging within the hormesis paradigm

Abstract

A coherent set of epidemiological data shows that the Mediterranean diet has beneficial effects capable of preventing a variety of age-related diseases in which low-grade, chronic inflammation/inflammaging plays a major role, but the underpinning mechanism(s) is/are still unclear. It is suggested here that the Mediterranean diet can be conceptualized as a form of chronic hormetic stress, similar to what has been proposed regarding calorie restriction, the most thoroughly studied nutritional intervention. Data on the presence in key Mediterranean foods of a variety of compounds capable of exerting hormetic effects are summarized, and the mechanistic role of the nuclear factor erythroid 2 pathway is highlighted. Within this conceptual framework, particular attention has been devoted to the neurohormetic and neuroprotective properties of the Mediterranean diet, as well as to its ability to maintain an optimal balance between pro- and anti-inflammaging. Finally, the European Commission-funded project NU-AGE is discussed because it addresses a number of variables not commonly taken into consideration, such as age, sex, and ethnicity/genetics, that can modulate the hormetic effect of the Mediterranean diet.

Keywords: Mediterranean diet; Nrf2; hormesis; inflammaging; stress.

Figure 1

Biphasic dose-response curve toward a hormetic stimulus. Under a certain threshold, the effect of a stimulus/stress on the measured trait is positive (improvement), whereas over this threshold it becomes detrimental/toxic. The range of hormetic doses is indicated as the “hormesis zone.”

Figure 2

Aging as a lifelong adaptation to stressors. From intrauterine life to old age, humans are constantly exposed to a series of stressors that includes physical and chemical pollutants and viral and bacterial antigens, as well as food-derived molecules that are sensed by a series of stress-responding mechanisms, leading to a lifelong adaptation. Depending on the outcome of this adaptation, the balance between pro- and anti-inflammatory parameters may be preserved or not, and, consequently, aging will either be delayed or age-related diseases may emerge. The Mediterranean diet is a powerful tool to counteract inflammaging and its consequences. Abbreviations: CR, calorie restriction; MedDiet, Mediterranean diet.

Figure 3

Beneficial components of the Mediterranean diet. Foods, nutrients, and micronutrients (ie, legumes, “good fats,” vitamins) provided by the Mediterranean diet contribute to its beneficial effects (antioxidant and anti-inflammatory profiles, prebiotic functions). Abbreviations: MUFAs, monounsaturated fatty acids; PUFAs, polyunsaturated fatty acids.

Figure 4

Critical and neglected aspects of the Mediterranean diet’s effect across individual, population, and environmental variables within a global perspective.Abbreviation: MedDiet, Mediterranean diet.