I would like to introduce you to cutting-edge research on primary aging, being carried out here in Quebec, in collaboration with Concordia University. Since 2013, we have been identifying new modulators of primary aging, also called calorie restriction mimetics, or even gerosuppressive agents. I will explain the basics of this research to you here, and more articles will follow to discuss the results in more depth and/or the role of lifestyle habits on healthy aging.

The science of anti-aging

Science in recent years has taught us that it is not systemic oxidation that is responsible for the aging of our cells. In contrast, some living organisms with higher-than-normal systemic oxidation levels live up to 10 times longer than other similar organisms. How is this possible? Why are we getting old? We will try to answer these questions.

Science from the past 15 years has made a phenomenal leap in this field, challenging one of the most important paradigms in biology: the very cause of aging. We now distinguish primary aging from secondary aging. The urge of our cells to age corresponds to primary aging and aging linked to lifestyle habits is defined as secondary aging. It is now obvious that we can act in prevention, to age better, by slowing down the processes of primary aging and by increasing the resistance of our cells. This will reduce the incidence of several diseases. Our research with Concordia University has led to significant advances in this area.

Let’s go back in time to better understand the future

Interestingly, it was in 1935 that scientific observations laid the foundation for what would enable us to know the real causes of aging. These are scientific observations related to the importance of the caloric content of foods versus their nutrient intake (Clive McCay, 1935). Yet 80 years later, high-calorie, low-nutrient foods are responsible for the obesity problems of our time.

Clive M. McCay (1898-1967) pioneered the observation of the effects of calorie restriction. It is this observation that has enabled the most important advances of the 20th century in understanding the metabolic processes and pathways associated with aging. By reducing the calorie intake by 30%, without reducing the intake of vitamins, minerals and essential elements, we can increase the lifespan of rodents by 30 to 50%. Subsequently, this phenomenon was demonstrated in yeast, nematodes, fruit flies, fish, mice and recently in Japanese macaques. Similar working mechanisms are present in all living organisms. These mechanisms were therefore preserved during evolution.

Unfortunately, these observations have been misinterpreted for 70 years. The explanation made sense: a decrease in calorie intake causes a decrease in basal metabolism, which reduces the level of systemic oxidation and allows for better longevity. A small machine works less quickly and therefore wears out less quickly. This is not the case, however. Calorie restricted animals have higher than normal systemic oxidation levels and fasting causes an increase in basal metabolism. What is happening then?

Growth and the urge of the body to age

Species that live longer, compared to similar animals, usually have much higher resistance to cellular oxidation, but also have maintenance and repair mechanisms that remain active much longer. We are talking about DNA repair, damaged proteins, cellular recycling processes (autophagy), etc. Add to that the maintenance of healthy mitochondria (our energy powerhouses that are at the heart of aging processes and many diseases), you get healthy aging. This is how, by increasing our resistance to aging and keeping our mitochondria healthy, it will be possible to prevent a large number of diseases associated with aging (by reducing their incidence).

You should know that the speed of aging is mainly linked to two processes for which our cells have developed molecular detectors:

  1. On the one hand, these detectors identify whether we have enough energy available in our food to develop when we are young and to age when we are old. These detectors will adjust the rate of growth and/or the rate of aging according to our intake of certain nutrients.
  2. On the other hand, certain mechanisms of maintenance and repair of our cells are inducible and animal cells react to molecules produced by plants for similar mechanisms.

Thus, it is possible to identify molecules that either reduce the body’s urge to age or increase the resistance capacities of our cells. We have developed a powerful approach that allows us to identify the best natural molecules that act on these cellular detectors of aging.

Important discoveries in Quebec

The research platform uses yeast to identify and understand how these natural compounds slow aging and make cells more resistant to physical stress. It has been a globally recognized research model for over 10 years. It is, among other things, due to this model that we owe the discovery of the mechanisms of action of resveratrol in the early 2000s.

We already have 8 scientific articles published in the journal with the highest ranking in basic research on primary aging. Over half a million spent. Our work presents the best results obtained to date, and the molecules used come from plant extracts.

The recently published results were obtained from specific extracts already known to have different health benefits. With Professor Titorenko’s team at Concordia University, we have identified new anti-aging molecules from extracts (PE for “plant extract”) which are numbered PE26 (Serenoa repens), PE39 (Hypericum perforatum), PE42 (Ilex paraguariensis), PE47 (Ocimum tenuiflorum), PE59 (Solidago virgaurea), PE64 (Citrus sinensis), PE68 (Humulus lupulus), PE69 (Vitis vinifera), PE72 (Andrographis paniculata), PE75 (Hydrastis canadensis), PE77 Trigonella foenumgraecum), PE78 (Berberis vulgaris), PE79 (Crataegus monogyna), PE81 (Taraxacum erythrospermum) and PE83 (Ilex paraguariensis). In the vast majority of cases, the biological activity is not linked to the molecules usually responsible for the health benefits of these plant extracts.

The results obtained relate to the average longevity and the maximum longevity. They also include analyzes on the metabolic activity of mitochondria, on the oxidation of membrane lipids, as well as on the oxidation of proteins, DNA of mitochondria, and DNA of the cell nucleus. These anti-aging extracts, also called geroprotectors or calorie restriction mimetics, increase the resistance of cells to oxidative stress and temperature. Improving cellular function reduces damage to cells while increasing their resistance to difficult situations. Since it is possible to act on two types of mechanisms (primary aging and maintenance mechanisms), we have also identified very important synergistic effects. The maximum impact observed so far is 7 times greater than that of resveratrol alone (over 700% higher).

The results of this research have clearly shown that the observed beneficial effects on longevity are linked to slowing the aging of cells and improving maintenance processes. These fifteen new groups of molecules join the six already discovered to form a bank of 21 new modulators of aging. We have filed two new patent families relating to these discoveries. More than 30 invention patents are expected to be developed from this research on slowing down aging, and the first applications are in the field of natural products.

The ultimate preventative medicine

“The Ultimate Preventative Medicine” is the title of a scientific article that was published in the prestigious journal Science in December 2015 by a great American researcher Matt Kaeberlein. It’s about reducing the incidence of diseases associated with aging, all together in one fell swoop to enable people to age healthy. The molecules we have discovered are new hopes for making it happen.

These natural molecules could help prevent all of the diseases associated with aging, not one at a time, but all at the same time. It is therefore a question of reducing the incidence of common conditions such as osteoarthritis, diabetes, cancer, heart disease, Parkinson’s and Alzheimer’s.

 

Originally published in the journal Vitalité QC: https://vitalitequebec-magazine.com/en/home/

 

 

References:

  • Barzilai, et al, 2012. The rationale for delaying aging and the prevention of age-related diseases. Rambam Maimonides Med J. 2012 Oct 31;3(4)
  • Costantini et al, 2017. The Greenland shark: A new challenge for the oxidative stress theory of ageing? Comp Biochem Physiol A Mol Integr Physiol. 2017 Jan;203:227-232.
  • Dakik P, Rodriguez MEL, Junio JAB, et al. Discovery of fifteen new geroprotective plant extracts and identification of cellular processes they affect to prolong the chronological lifespan of budding yeast. Oncotarget. 2020;11(23):2182-2203. Published 2020 Jun 9. doi:10.18632/oncotarget.27615
  • Eric Simard, Dr en biologie et Jacques Lambert, MD. 2018. Vivre jeune DEUX fois plus longtemps. Marcel Broquet la nouvelle édition. 270 pages.
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  • McCay, C. et al, 1935. The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size: One Figure. The Journal of Nutrition, Volume 10, Issue 1, July 1935, Pages 63–79, https://doi.org/10.1093/jn/10.1.63
  • Mikhail V. Blagosklonny, 2013. Big mice die young but large animals live longer. AGING, Avril 2013, Vol. 5 No 4.