The key role of insulin for a increasing lifespan

In the previous article (understanding metabolismo for healthy nutrition), we introduced the concept of “metabolic pathways”, an key topic to understand how to intervene through our diet. In this we will explain how to orchestrate a nutritional strategy in favor of a healthy longevity.The main actor of the first metabolic pathway is a hormone: InsulinHormone produced by Langerhans island cells of the pancreas. It stimulates the entry of glucose into the cells, subtracting it from the blood and thus lowering blood sugar. It induces the use of glucose both to produce energy and for the synthesis of glycogen and fats., able to feel the availability of carbohydrates (sugars) and proteins in our body and kick off all those biochemical processes related to them. This hormone does not read lipids, i.e. fats ingested in the body, but stimulates their deposit.Insulin is therefore to all effects an anabolic hormone as it promotes the entry of glucose into cells and the lipides into fat cells as well as it stimulates protein synthesis through mTORThe mTOR (mammalian target of rapamycin) is a set of enzymes (route) that react to food-nutrients, breaking them down and recombining them to build new proteins useful for the "growth of the body". They react to specific hormonal stimuli (Insulin and IGF-1) thus becoming the center of control of growth and cell proliferation in metabolism. This metabolic route is also responsible for the elimination of old and defective cells (Cellular Autophagy) with the double advantage of recycling the fundamental components to produce new cells and eliminate them to prevent them from triggering degenerative and inflammatory processes..In fasting states, on the other hand, another hormone is produced, Glucagon, which allows to maintain a constant blood sugar level (glucose), even in the absence of the introduction of sugar, by inhibiting the protein synthesis, promoting cell autophagy and stimulating the oxidation of fats (lipolysis).

Recalling the “survival principle” of the species, we know that all the metabolic processes lead on increasing survival chance to the reproductive maturation of living organisms, have as a countereffect on their lifespan reduction over time. Therefore the stimulus of insulin, on the one hand pushes to accelerate the structural completion of the organism (reproductive capacity), but on the other hand accelerates its decay.On the contrary, the action of glucagon counterbalances the effects of insulin and counteracts the decay of the body. Everything lies in governing these two hormones in fact, “modulating” the insulin cycle is one of the fundamental targets of the strategy for healthy-ageing and lifespan extension.

Steering the mTOR protein pathway to combat ageing

The second metabolic pathway (mTOR) is the one used to build the fundamental building blocks of our life cycle: proteins. Alerted by insulin, mTOR activates the protein production process by combining the amino acidsAmino acids are the basic substances that make up proteins. Each protein is characterized by a precise sequence of amino acid "bricks". Some are produced by the body by processing food, others, which the body cannot synthesize, must be taken directly with food. made available. Also for this process, the main physiological objective is the organism’s growth over longevitymTOR also plays this role of “protein maker” through a process of “recycling” old cells: breaking them down into their components, reusing them to create new proteins and releasing new units of energy.This recycling process is called “autophagy”, an essential activity in reducing the presence of aging-promoting components, as senescent cells produce inflammation and defective cell replications, which trigger several chronic diseases.

How to “hibernate” the metabolism by stimulating the AMPK

The third metabolic pathway (AMPKAMPK (AMP-activated protein kinase) stands for monophosphate-activated adenosine protein kinase. It is an enzyme that plays a critical role in cellular homeostasis and a signaller of the body's energy level: it signals whether there is enough in the body to activate cellular functions such as glucose absorption, fat oxidation, and the formation of new mitochondria. In case the energy is not enough, it stops the activity of creation of macro-molecules by pausing the production activity. The AMPK way is a "metabolic regulator".) is also strongly stimulated by the way we feed ourselves. Its role is to govern the other 2 metabolic pathways by trading off among cell growth and cell hybernation, when it is more appropriate to pause the production process of macro-molecules in order to ensure the survival of the organism.AMPK has the ability to feel how much energy (ATPAdenosine triphosphate (ATP) can be defined as the "energy currency" of the cell, the instrument through which the cell carries out processes that require energy (endoergonic) and is produced by reactions that release energy (exergonic).) is produced during the catabolic phase and other generation processes.The more energy it senses, the lower its inhibiting activity, allowing the metabolic production chain to turn at its maximum. On the contrary, when it feels a reduction in energy level, it strengthens its inhibiting activity, putting the system on pause and activating its spare resources: i.e. increasing glycolysis or releasing stored carbohydrates, activating lipolysis (the availability of stored fatty acids) and finally enhancing autophagy.For the same survival principle stated above, it is clear that the “stand-by” phases are pro-longevity; to stimulate them, it is necessary to reduce the level of energy introduced in our body.

Pro-longevity nutritional strategies

Reducing the glucose level and circulating proteins as well as the daily caloric intake are the key elements of any nutritional plan to increase our longevity chance.The glucose reduction, by eliminating or strongly reducing the carbohydrate component of our diet, is a key element to soothe the metabolic pathway of insulin and reduce the body’s energy level.It should be noted that glucose is an essential element for our brain functioning and other essential biochemicals processes, therefore the reduction should be modulated in order to avoid negative side effects.Calorie restriction tout-court, i.e. eating less than what would normally be necessary, is another technique to act on all metabolic pathways, reducing insulin activity, increasing autophagy and stimulating AMPK for using the stored reserves (i.e. lipolysis).Calorie restriction is a drastic method that should not fall into malnutrition, because this would trigger a mechanism of structural damage and would also affect our immune system capabilities. We speak of a 20% max reduction in calories ingested compared to those needed in a balanced situation (calorie requirements).

Application example for this strategy

For example, the balanced caloric intake of a woman between 30 and 50 years old, who has a weight of 60kg, with clerical work and no regular sports activity, is about 1840 Kcal.Assuming that she eats exactly for her needs and wants to activate a caloric restriction, this lady should consume between 1,400 and 1,500 kcal per day for the same lifestyle. Alternatively, she could continue to eat for 1840 kcal but start practicing sports regularly (3 times a week, for a total of 4-6 hours) because this would bring her calorie requirements to 2,200 kcal, 20% more than she consumes.It is clear that, if the lady in question had a basic diet higher than 1840 kcal already, the reduction in diet or increase in physical activity should be such as to compensate for this excess.

the “sustainable” alternative to caloric restriction

Unfortunately, caloric restriction, even when combined with physical activity, is a difficult nutritional practice to adopt in the long term, explaining the failure of many diets that focus on this strategy . There are 2 main types of issues on the long term: metabolic and psychological ones.Put under pressure by the lower amount of energy ingested and / or the increase in physical activity, the metabolic pathways stimulate the centers of energy regulation to seek food, creating a strong psychological pressure on the subject who still has to counteract the natural demand of the body for energy balanceA more sustainable nutritional strategy but equally effective in providing the right signals to the metabolism is the Intermittent Fasting.Certain periods of fasting, i.e. above a minimum time threshold, stimulate the metabolic pathways (such as calorie restriction) but also the activity of so-called “counter-balancing hormones” (e.g. Adrenaline, Noradrenaline and Growth Hormone, glucagon) that help to keep the energy metabolism in balance, also giving a feeling of well-being and euphoria, silencing the hunger hormone.In fact, those who apply intermittent fasting, in its different forms, do not have the same chronic hunger feeling as those who use calorie restriction.

Possible aids to low-calorie regimes: amino acids

There are other ways to reduce protein intake, one of which is the use of Rapamycin, which acts directly on the metabolic pathway mTOR inhibiting its activity. This substance, extracted from an Easter Island mushroom, also has an immunosuppressive function, useful in several chronic diseases of inflammatory origin. Its use pushes to autophagy and reduces the sense of hunger, because it slows down the “production chain” of proteins. The advantage in terms of longevity and health is theoretically fascinating.Its use is still debated for the intrinsic risks related to its impact on the immune system, exposing it to greater risks of viral infections. Its correct dosage is also under discussion, because its prolonged use can generate insulin resistance and alterations in cholesterol and triglycerides, the road to making it a long-life drug is still long.

A final consideration concerning hypoproteic regimes. All the proteins produced by our body, and they are several hundred thousand, are based on the combination of elementary bricks called amino acids. There are 20 types of amino acids grouped in 2 families: essential (9) and non-essential (11), the latter can be produced autonomously by our organism while the essential ones must be taken through the diet.Our organism has a fundamental need of them and does not have great storage capacity of these components; we have seen that protein excess is a risk factor for chronic diseases, while a partial deficiency can stimulate a mechanism such as autophagy, but a prolonged deficiency has significant impacts on the degeneration of muscle structure and other consequences.Diets must modulate protein intake according to the health status and age of the subject, favoring its presence when the body is growing, but reducing it in mature age.A different approach is needed for advanced age (over 65 years) people where the protein requirement increases again due to the presence of anabolic resistance and the progressive loss of muscle reserves (sarcopeniaThe term sarcopenia refers to the progressive loss of muscle mass and related decrease in strength; in addition to the volume reduction in muscle mass, it also leads to a worsening of the latter because:
• the muscle is slowly replaced by adipose tissue (fat),
• the junctions between muscle and nerve fibres (neuromuscular junction) tend to degenerate,
• muscle oxidative stress increases.
)During adulthood and for healthy people, pro-longevity diets should provide a reduced protein content, giving priority to those of plant origin.Plant proteins, unlike animal proteins, are not completely bioavailable for human metabolism. This means that for the same amount of food (energy) taken, the protein value is much lower if it is of vegetable origin.In the next in-depth studies, we will clarify the ideal sources for protein nutrition and nutritional integration strategies to modulate the metabolic pathways in a pro-longevity perspective.