Several studies carried out in recent years have indicated that reducing and combining meals in well-defined time intervals has cardiovascular, neurological, functional, oncological and antiaging benefits.

As a result of this, a booming alternative dietary approach so-called intermittent fasting was born. This type of a nutritional tool aims to establish a caloric restriction in the diet, limiting energy intake, which triggers a series of metabolic processes that contribute to reduce inflammation, cholesterol, blood pressure and help to decrease oxidative stress and prolong the lifespan by slowing down cellular aging.

But how does this calorie restriction affect us metabolically?

The answer could be related to the activation of a number of own mechanisms for obtaining cellular energy.

These kinds of mechanisms are related with the action of Sirtuins, a type of dependent NAD+ enzymes belonging to the deacetylase family. These enzymes are involved in cellular metabolism and the function of numerous mitochondrial proteins, regulating the expression of certain genes.

Its origin comes from Silent mating type Information Regulation two or Sir2; a longevity gene found inside the yeast of beer, which, despite its single-celled nature, can age. In 1997, MIT professors David Sinclair and Lenny Guarente discovered that the main activation of the same gene was enough to suppress DNA instability and thus increase yeast longevity.

In mammals, Sir2 is known as SIRT1, and plays various roles in regulating cell proliferation, differentiation, stress response, energy homeostasis, and, indirectly, in aging and cancer. The fact that NAD+ is an important cofactor in metabolic reactions and the energy transport chain makes these sirtuins act as stress detectors, targeting not only histones in the nucleus but also other proteins in the cytoplasm and mitochondria.

While at least seven proteins in the sirtuins family (Sirt1-7) are known, the Sirt-1 and Sirt-3 are the ones that are most related to improving health and longevity parameters:

  1. The activation of Sirt-1 plays an important role in energy homeostasis, modifying the transcription according to the nutritional status. It has been found that during calorie restriction diets, Sirt-1 levels are increased, regulating metabolic expenditure and inhibiting apoptosis processes. At the same time, it negatively regulates the action of the telomerase gene (hTERT) and promotes cell arrest and DNA repair that indirectly increase longevity.

It also appears to promote anti-inflammatory actions and a global metabolic improvement in obesity situations and glucose intolerance and it functions as a positive regulator of pancreatic insulin secretion.

  1. On the other hand, mitochondrial sirtuin 3 (Sirt3) is responsible for mediating increased energy demand during caloric restriction to increase equivalent energy production. It is responsible for deacetyling, and thus activating mitochondrial enzymes related to fatty acid oxidation, amino acid metabolism, electron transport chain and antioxidant defenses.

In this way, the effect of Sirt3 causes some resistance against reactive oxygen species (ROS), decreasing the quantity of free radicals and preventing mitochondrial deficits associated with aging and neurodegeneration.

Therefore, it seems that the physiological basis of intermittent fasting as a result of siRT1 expression is indirectly related to longevity and lifespan as its impact is more effective on protection against aging-related diseases such as diabetes, cancer and neurodegeneration. Nevertheless, it is important to take into account that the results of caloric restriction depend on individual genetic characteristics.