The beneficial effects of the Mediterranean diet (MD) had been first observed about 50 years ago. Consumption
of fresh vegetables and fruits, cereals, red wine, nuts, legumes, etc. has been regarded as the primary factor for protection
from many human pathologies by the Mediterranean diet. Subsequently, this was attributed to the presence of polyphenols
and their derivatives that, by exerting an anti-inflammatory and anti-oxidative effect, can be involved in the prevention of
many diseases. Clinical trials, observational studies and meta-analysis have demonstrated an antiageing effect of MD
accompanied by a reduced risk of age-related pathologies, such as cardiovascular, metabolic and neurodegenerative
diseases, as well as cancer. The scientific explanation of such beneficial effects was limited to the reduction of the
oxidative stress by compounds present in the MD.
However, recently, this view is changing thanks to new studies aimed to uncover the molecular mechanism(s) activated by
components of this diet. In particular, a new class of proteins called sirtuins have gained the attention of the scientific
community because of their antiageing effects, their ability to protect from cardiovascular, metabolic, neurodegenerative
diseases, cancer and to extend lifespan in lower organisms as well as in mammals. Interestingly, resveratrol a polyphenol
present in grapes, nuts and berries has been shown to activate sirtuins and such activation is able to explain most of the
beneficial effects of the MD.
In this review, we will highlight the importance of MD with particular attention to the possible molecular pathways that
have been shown to be influenced by it. We will describe the state of the art leading to demonstrate the important role of
sirtuins as principal intracellular mediators of the beneficial effects of the MD. Finally, we will also introduce how
Mediterranean diet may influence microbioma composition and stem cells function.