In recent years, studies have been conducted indicating that reducing and spacing meals at well-defined time intervals has cellular aging, cardiovascular, neurological, functional and oncological benefits.
Therefore, intermittent fasting is booming as an alternative dietary approach. This type of nutritional approach aims to establish caloric restriction in food by limiting the dietary energy intake, which triggers a series of metabolic processes that help reduce inflammation, cholesterol, blood pressure and help lower oxidative stress and extend lifespan by slowing down cellular aging.
But what metabolic effect does this calorie restriction have?
The answer could be related to the activation of a series of adequate mechanisms for obtaining cellular energy.
These types of mechanisms are related to the action of Sirtuins, a type of NAD+ dependent enzymes belonging to the deacetylase family.
These enzymes participate in cellular metabolism and in the function of numerous mitochondrial proteins, regulating the expression of certain genes.
They originate in the Silent mating type Information Regulation two gene or Sir2; a longevity gene found in beer yeast, which despite its unicellular nature, is capable of aging.
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.
Sir1-7 sirtuins functions
In mammals, Sir2 is known as SIRT1, and plays a number of roles in cell regulation 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, prompts sirtuins to act as stress detectors, targeting not only histones in the nucleus, but also other proteins in the cytoplasm and the mitochondrion.
At least seven proteins of the sirtuin family (Sirt1-7) are known, but Sirt-1 and Sirt-3 are two of the most closely related to the improvement of health and longevity parameters:
Sirt-1 activation plays a role in energy homeostasis, modifying transcription according to nutritional status.
During calorie restriction diets, Sirt-1 levels have been found to increase, regulating metabolic expenditure and inhibiting apoptosis processes. In turn, it negatively regulates the action of the telomerase gene (hTERT) and promotes cell arrest and DNA repair, which indirectly increase longevity.
It also seems to promote anti-inflammatory actions and an overall metabolic improvement in situations of obesity and glucose intolerance, and it works as a positive regulator of pancreatic insulin secretion.
On the other hand, mitochondrial sirtuin 3 (Sirt3) is concerned with mediating the increase in energy demand during caloric restriction to increase the equivalent energy production. It’s responsible for deacetylating, and thus activating mitochondrial enzymes related to the β oxidation of fatty acids, the metabolism of amino acids, the electron transport chain and antioxidative defenses.
Thus, the effect of Sirt3 causes some resistance against reactive oxygen species (ROS), decreasing the amount of free radicals and preventing mitochondrial deficits related to aging and neuro-degeneration.
Therefore, it seems that the physiological basis of intermittent fasting as a consequence of the expression of SIRT1 is indirectly linked to longevity and lifespan, and its impact is more effective on the protection against diseases related to aging, such as diabetes, cancer and neurodegenerative diseases. Lastly, it should be understood that the consequences of caloric restriction depend on individual genetic characteristics.
Date: March 26th, 2020
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