What are sirtuin proteins?
Sirtuins are proteins (more specifically enzymes) made by our body under the influence of some of our genes: Sirt1 to Sirt7 (7 genes for all mammals, including humans).
They act essentially in the presence of a coenzyme: NAD+ (a derivative of vitamin B3), and are involved in various cellular biological processes:
- energy production,
- cell and DNA repair, autophagy,
- the cellular stress response,
- apoptosis (the suicide of our old cells) and cellular senescence,
- tissue sensitivity to hormones,
- insulin secretion and sensitivity,
- the functioning of the liver and its regeneration,
- fat burning,
- adaptation to caloric restriction,
- the processes of inflammation and oxidation…
With regard to anti-aging, it appears that, in an unfavorable nutritional environment (such as caloric restriction, or a deficiency in certain nutrients, for example), sirtuins trigger specific functions in our cells, which would allow them to survive longer, until you regain “normal” nutrient intake.
In fact, studies of simple organisms (like yeast or worms) generally show that turning off Sirt genes shortens their lifespan while turning them on lengthens it. Hence the interest in sirtuins.
The researchers then wondered if it was possible to activate these functions by other means. In particular, various studies have shown that an intake of resveratrol could achieve this in mice (see below).
Role of sirtuins
They have a very important role in the balance of metabolism and energy production in our cells. Some act mainly in our mitochondria* by reducing the free radicals generated during this production (sirtuins 3 to 5) (1). They also increase our levels of antioxidant enzymes.
Sirtuins would promote resistance to stress, the survival of neurons, and could prevent the premature death of damaged cells. They would thus have a protective role in neurodegenerative diseases (2), and also a beneficial role in the prevention of diabetes, cancers and finally, in the aging of the body.
The known effects of sirtuins
To put it simply, let’s say that these enzymes are involved in regulating the metabolism of sugars and fats in the body, when these are “burned” with oxygen, for our energy production (3). In particular, sirtuins intervene here by reducing the production of free radicals in our mitochondria and the processes of oxidation.
In recent years, we have been hearing about sirtuins for their effect on longevity and against diseases related to aging such as cancer, neurodegeneration and cardiovascular disease. It is true that in animals, the activation of sirtuins has given very interesting results against these diseases (5)(11).
In fact, each sirtuin has one or more particular functions. Experiments have shown that high levels of sirtuins can lengthen the lifespan in mice, worms, yeasts… They could also act by stimulating our famous stem cells pluripotent, in particular by the SIRT6 gene (8)
Specifically, Sirt1 is activated during periods of calorie restriction and produces sirtuin 1. This has a slowing effect on the insulin metabolic pathway and Igf1 (or Insulin-like growth factor, the main derivative of growth hormone), related to carbohydrate metabolism. In the end, this allows a 30% gain in longevity in small animal studies.
We know that Sirt2 is involved in the anti-proliferative effect of resveratrol on cancer cells.
By artificially raising the levels of sirtuins 6 in mice, by genetic manipulation, they live longer (7).
On the other hand, researchers have shown a slowing down of aging by activating the gene Sirt2 in yeasts (3).
Can we activate our sirtuins?
The calorie restriction would therefore have its well-known effect on longevity (in animals) in relation to the activation of the sirtuins that it causes (in particular sirtuin 1).
the intermittent youngin addition to improving insulin sensitivity and DNA repair, would increase the activity of sirtuin genes (6).
The state of ketosis (and the production of ketone bodies) obtained in a diet low in sugars (low carbohydrate: for example Atkins type, or other ketotic diets) or during a period of fasting, is associated with an increased activity of sirtuins.
Physical activityin addition to its general anti-inflammatory effect increases Sirt1 (13).
Exposure to intense heat like the sauna, for example, would go in the same direction.
the resveratrol, in addition to being a good antioxidant, is in particular one of the activators of Sirt1, which would explain its action on longevity. In particular, it stimulates the activity of mitochondria, which tends to decrease with age. Several studies have in fact shown an extension of the lifespan of mice on a high-calorie diet and supplemented with resveratrol (9)(10)(14).
Other polyphenols like fisetin and the quercetin (known to be senolytics), as well as butein, and piceatannol would have similar effects.
The melatonin known to regulate sleep does the same, and has demonstrated anti-aging effects.
Increase NAD+ in our cells with nicotinamide riboside or NMN (see vitamin B3 and longevity), can also activate sirtuins (Canto et al., 2012; Yoshino et al., 2011).
Supplementation with leucine also increases Sirt1 in obese mice fed a high-fat diet (Hongliang Li 2012).
Sirtuin activating drugs
Resveratrol has proven to be one of the best Sirt1 activators to date. That said, the doses of resveratrol that work in mice, transposed to humans, turn out to be very important. Also, study laboratories are looking for drugs capable of increasing Sirt1 with lower doses.
For the moment, no miracle drug in sight.
A sirtuin diet (sirtfood) to stay in shape with age?
That said, without removing the multiple beneficial effects demonstrated by resveratrol or calorie restriction, other studies moderate (even contradict) some of the results seen above. So don’t rush into classifying sirtuins as the anti-aging solution. (The controversial world of sirtuins Weiwei Dang 2012)
Pay attention again to fashion effects. Some nutritionists have even invented the SirtFood diet which would activate sirtuins, to help lose weight and live longer. It is rather restrictive in calories (which is not surprising when you are trying to lose weight) and recommends foods called “sirtuin activators” such as certain citrus fruits, broccoli, red wine and chocolate… It may seem interesting but it It is difficult to say whether this diet will have the same effects on humans as on yeasts. In any case, the marketing effect is certain for the moment.
So it still takes time to find out more.
Sirtuins are indeed involved in the mechanisms of cellular aging in humans, as well as in cellular protective mechanisms making it possible to fight against various degenerative diseases.
However, some studies contradict each other on the precise role of sirtuins in caloric restriction. Moreover, there is no evidence that the improvements in longevity recorded in worms or mice are transposable to humans.
Thus, it still seems premature to propose a panacea for longevity based on the activation of sirtuins.
However, let’s not throw the baby out with the bathwater. We now know that the sirtuin pathway is indeed part of the metabolic pathways that influence longevity (or aging), such as the insulin/Igf-1 pathway, the mTOR, AMPK, FOXO pathway, etc. Also, all this that will go in the direction of its activation should go in the direction of health and lifespan. In fact, a little observation shows us that what activates sirtuins is not specific to them, and also influences, most often, the other metabolic pathways linked to longevity. A bit as if scientists were gradually discovering different parts of the same mechanism protecting longevity.
Similarly, sirtuins or not, resveratrol mimics the effects of caloric restriction, and its protective effects in aging humans have been demonstrated time and time again. Ditto for the interest of polyphenols in food.
Finally, sirtuin activation is achieved by methods or substances that are already known to have longevity-enhancing effects. So, to date, without going so far as to adopt a hypothetical “special sirtuins” diet, without really betting on wine, which in fact provides low doses of resveratrol, the variety in fresh, colorful and quality fruits and vegetables , light diet and intermittent young people, exercise and a healthy lifestyle in general, remain safe bets.
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