Taken from chapter 3.4 of the book “Live Young, Longer”.
We explained in a previous article (Olive polyphenols and Vitoli products – article 1: Primary aging), that it is possible to group animals that age particularly well under two main approaches:
- Those whose primary aging processes are slowed down;
2. Those who do more maintenance and repair.
Our recent discoveries with Concordia University have clearly demonstrated a powerful synergistic effect where it is possible to combine the health benefits of these two approaches. To find out more about this research, you can consult the “Research” tab on the “Eric Simard, Priority Healthy Aging” website: https://esimard.com/en/research/
In a second article (Olive polyphenols and Vitoli products – article 2: The benefits), we described polyphenols from olives as “gerosuppressive” agents based on the discoveries of Menendez and his collaborators (2013) and more recently on those of Pablos et al. (2019). They act on the first facet. As for resveratrol, it acts on the second facet: maintenance and repair mechanisms.
Do more maintenance and repair
Take the example of the naked mole rat, this small rodent, the size of a mouse, is capable of living 30 years; which is up to 10 times the normal longevity of a mammal of this size. It has higher than average oxidation levels and relatively short telomeres. What seems to explain its great longevity, is its maintenance and repair capacities.
By comparing organisms of similar size (mice, naked mole rats and bats), it is possible to note that these organisms of the same size with similar development rates (gestation of 20 days vs. 70 and 45 to 70 days respectively) have completely different life expectancies. A mouse will live for around 3 years, compared to naked mole rats and bats which will live from 30 to 40 years; ten times longer.
It is their significantly higher maintenance and repair capacities, or at least, longer preserved capacities during their lifespans, which would explain this extraordinary longevity. Young living organisms usually have very good maintenance and repair capabilities, which will gradually decrease as they age. These organisms which live much longer than the average (naked mole rat and bat) maintain their capacity for maintenance and repair much longer.
Resveratrol: a very large number of studies
To date, resveratrol alone has more than 5,000 scientific publications. A recent study concluded that the best alternative to caloric restriction in humans would be to reduce our calorie intake, exercise regularly and consume a dietary supplement of resveratrol. The optimal dose of resveratrol for an adult is practically impossible to take just from food sources (wine, grapes, dark chocolate, blueberries, and peanuts).
There are already 19 clinical studies listed on the pharmacokinetics of resveratrol in humans. Its highest level of blood concentration appears after 30 to 90 minutes. Its half-life is approximately nine hours. About 70% of the dose consumed is absorbed, but only small amounts of the intact molecule are detectable in the blood. The extremely rapid conjugation metabolism (binding to other molecules) greatly reduces the bioavailability of resveratrol. However, it seems that these same metabolites (conjugated molecules) accumulate in different tissues of the body and are linked to the beneficial effects on health.
Mechanisms of action
In 2003, a scientific publication in the famous journal, Nature, demonstrated that resveratrol stimulates one of the metabolic anti-aging pathways through a protein called sirtuin 1 (SIRT1). Sirtuins are very well preserved proteins during evolution. That is to say, we find them with similar functions in all living organisms, ranging from single-celled organisms (yeast) to mammals, including insects.
Sirtuins play a very important cellular role in the mechanisms of aging, both at the level of cellular functioning and at the level of the mitochondria (the energy powerhouses of our cells). Thus, these proteins can activate a large number of genes essential to the body’s natural antioxidant defenses, as well as cellular repair mechanisms.
Part of the beneficial effects of resveratrol is explained by its ability to modify the use of energy intake as if the body were suddenly in danger of death. Maintenance and repair mechanisms are thus strongly stimulated at the expense of energy storage and growth processes. Resveratrol would therefore improve energy metabolism (obesity, diabetes, metabolic syndrome), while allowing a preventive effect for a large number of diseases.
Resveratrol also acts on aging by activating certain proteins involved in primary aging such as AMP-activated protein kinase (AMPK) and by reducing inflammatory factors NF-κ B (nuclear factor kappa B), TNFα (Tumor necrosis factor α) and IL-6 (interleukin 6), as well as the reduction of free radicals. Another publication in the prestigious journal, Nature, identified a new mechanism of action (TyrRS-PARP-1) of resveratrol that would be 1000 times more sensitive (activated in quantities 1000 times lower) to its known action on sirtuins. The research continues.
Resveratrol not only mimics the longevity effect of calorie restriction (calorie restriction mimetic), but it also activates several mechanisms that improve energy production in the mitochondria. It is a natural molecule that has been widely studied for its health effects, but for which much information is still missing to fully understand all of its benefits. Vitoli® Healthy Aging brings together two main approaches in a single product: modulators of primary aging and molecules acting on maintenance and repair mechanisms.
- Baur, J.A. 2010. Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev. Apr;131(4):261-9. Review.
- Diaz-Gerevini et al, 2016. Beneficial action of resveratrol: How and why? Nutrition. 2016 Feb;32(2):174-8. doi: 10.1016/j.nut.2015.08.017. Epub 2015 Sep 25.
- Newgard, C.B., Pessin, J.E. 2014. Recent progress in metabolic signaling pathways regulating aging and life span. J Gerontol A Biol Sci Med Sci. Jun;69 Suppl 1:S21-7. Review.
- Sajish and Schimmel, 2015. Human Tyr-tRNA synthetase is a potent PARP-1 activating effector target for resveratrol. Nature. 2015 Mar 19; 519(7543): 370–373.
- Shakibaei, M., Harikumar, K.B., Aggarwal, B.B. 2009. Resvératrol addiction: to die or not to die. Mol Nutr Food Res. Jan;53(1):115-28. Review.
- Timmers, S., Hesselink, M.K., Schrauwen, P. 2013. Therapeutic potential of resveratrol in obesity and type 2 diabetes: new avenues for health benefits ? Ann N Y Acad Sci. Jul;1290:83-9. Review.
- Tomé-Carneiro, J., Larrosa, M., González-Sarrías, A., Tomás-Barberán, F.A., García-Conesa, M.T., Espín, J.C. 2013. Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des. 19(34):6064-93. Review.