Gerosuppressive Agents

Table of Contents

Primary aging and secondary aging
Interventions to slow aging in humans: are we ready?
Calories and sugar; at the heart of aging
Calorie restriction mimetics
Gerosuppressive agents

Here is a term that is probably new to most of you. The most interesting thing is that this is the subject of an ambitious research program carried out here in Quebec with the support of the Natural Science and Engineering Research Council of Canada (NSERC) for 7 years now. Our research aims to identify new gerosuppressive agents: molecules capable of modulating the metabolic pathways of primary aging. Recent discoveries have shown that it is possible to act on aging in order to maintain our capacities for longer periods of time. Vitoli® Healthy Aging was developed specifically for this reason.

Since the early 2000s, scientists have made important discoveries that challenge previously developed theories of aging. Aging is not just the result of wear and tear caused by oxidation; the molecules produced by the energy production of our cells. It took more than 10 years for a new theory to be defended in 2013 by certain scientists in the field, giving reason to a researcher, who put forward this hypothesis in 1957 (George C. Williams, 1926 – 2010: antagonistic pleiotropy (1957) ). It was later renamed by a great American researcher (Mikhail V. Blagosklonny): the theory of hyperfunction.

Here are some elaborations to help you better understand the scope of this research by discussing the following points:

Primary aging and secondary aging
Interventions to slow aging in humans: are we ready?
Calories and sugar; at the heart of aging
Calorie restriction mimetics
Gerosuppressive agents

Primary and secondary aging

Research on aging has shown that there are two main categories of aging: primary and secondary. Primary aging refers to the body’s urge to age; cellular function that causes aging (which is fairly new and better understood since approximately the year 2013). Secondary aging, for its part, depends on our lifestyle, on the following 4 major factors: diet, physical activity, stress management (which includes the quality of sleep), and the quality of social life.

There is a fifth factor that I have classified as a facilitating factor, since it facilitates the adoption of healthy habits related to the four factors mentioned. It’s about being fundamentally positive. To be fundamentally positive means that you have an almost unwavering positive outlook on the past, on the present, and above all, you are confident in the future. Fundamentally positive people even go so far as to rate their health more positively than it really is. This positivism promotes the adoption of healthy lifestyle habits. Secondary aging is therefore influenced by our lifestyle and our state of mind.

Primary aging, on the other hand, can be influenced by certain molecules capable of improving the functioning of our cells by increasing our repair capacities or by reducing the body’s urge to age.

Interventions to slow aging in humans: are we ready?

This is the title of a scientific article published in January 2015. 30 of the most important scientists in the field of aging have come together to publish an article shedding light on the possibility of acting on aging (Longo et al, 2015 : Interventions to Slow Aging in Humans: Are We Ready?). It is possible to act on human aging in order to add years of quality to life and to maintain our capacities for longer periods of time.

Another expert in the field, Dr Kirkland, of the Mayo Clinic’s Kogod Center on Aging, wrote in his book Aging: The Longevity Dividend (2016): “it will be possible to push back, prevent, reduce or treat major related diseases, all together, at the same time.”. This is also what is described by another great American researcher, Matt Kaeberlein of the University of Washington, who called this approach “the ultimate preventative medicine“. The molecules that modulate primary aging could make it possible to increase longevity not by prolonging the state of old age, weak or sick, for longer, but by preserving the biological functions in a state similar to that of a younger organism.

To understand how this is possible, it is necessary to go back to 1935 to learn about the discoveries related to calorie restriction.

Calories and sugar at the heart of aging

It is interesting to note that as early as 1935, scientific observations already emphasized the importance of the caloric content of foods versus their nutritional 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, you can increase the lifespan of rodents by 30 to 50%. Subsequently, this phenomenon was demonstrated in yeast, nematode, fruit flies, fish, mice and recently in Japanese macaques. The metabolic benefits have also been studied in human clinical studies. Similar working mechanisms are present in all living organisms. These mechanisms were therefore preserved during evolution.

Calorie restriction mimetics

Calorie restriction helps: improve glucose management, reduce inflammation and body weight, lower triglycerides and bad blood cholesterol, increase good cholesterol, decrease the level of growth hormones, reduce the risk of cancer, preserve the functions of stem cells, improve the metabolism of mitochondria, reduce the loss of muscle mass, preserve structure and cognitive functions, etc.

These spectacular results are possible because calories, and especially sugar, are at the heart of the aging process. The science of recent years has taught us that when the body is at risk of lacking energy, at the limit of its caloric intake to survive (calorie restriction), it then directs all its energy capacities towards the mechanisms of maintenance and repair. It then stops the energy expenditure for growth; this same energy expenditure causing aging later in life (primary aging). Thus, the lack of calories, without causing a nutritional deficit, leads to a slowing down of aging and an improvement in the general state of health. Unfortunately, this is an extremely difficult lifestyle choice to make. It is also for this reason that a large number of research laboratories are working to discover molecules that could have similar effects: mimicry.

From the moment these molecular mechanisms were linked to aging, in the mid-2000s, it was possible to search for molecules that could influence these processes. Some natural molecules have effects similar to calorie restriction. There are very few. The molecules capable of slowing down primary aging were then called “calorie restriction mimetics”.

We now call them gerosuppressive agents; from the Greek “gero” which means aging and “suppressor” for the slowing down of the process. This term better represents the objective pursued. The mimicry of calorie restriction was not intended to reduce calorie intake, but to replicate the benefits by slowing down primary aging.

In 2013, a Spanish research group used this term to categorize the multiple health benefits of olive polyphenols by linking them to aging processes. A second article, from another research group, confirmed this assertion in 2019 with a very comprehensive literature review (194 references) which summarizes the cellular mechanisms, animal models and clinical studies carried out.

As mentioned at the beginning of this article, Vitoli® Healthy Aging has been specifically developed to act on aging. We have added resveratrol to the exclusive olive polyphenols of the Provitol® Complex to reflect an important discovery made with Concordia University. Resveratrol is a modulator of the proteins responsible for cellular repair: sirtuins. A recent scientific article reports 244 clinical studies published on this molecule, and 27 others were still in progress when it was published in 2019.

Thus, Vitoli® Healthy Aging is a product marketed to help you maintain your abilities as long as possible. It is authorized for sale by Health Canada with the number NPN800633775 as well as the claim, “Provides antioxidants”.

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References:

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.
de Pablos et al, 2019. Hydroxytyrosol protects from aging process via AMPK and autophagy; a review of its effects on cancer, metabolic syndrome, osteoporosis, immunemediated and neurodegenerative diseases. Pharmacological Research 143 (2019) 58–72.
Eric Simard, Dr en biologie. 2016. Vivre jeune plus longtemps ; Chapitre 3.2, Les polyphénols d’olives et la diète méditerranéenne. Marcel Broquet la Nouvelle édition. 364 pages.
Galiniak S, Aebisher D, Bartusik-Aebisher D. Health benefits of resveratrol administration. Acta Biochim Pol. 2019 Feb 28;66(1):13-21. doi: 10.18388/abp.2018_2749. PMID: 30816367.
Kaeberlein, 2015. Healthy aging: The ultimate preventative medicine. Science, 2015 Dec 4 ;350(6265) :1191-3.
Menendez et al, 2013. Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil. A new family of gerosuppressant agents. Cell Cycle 12:4, 555–578; February 15, 2013.
Mikhail V. Blagosklonny, 2013. Big mice die young but large animals live longer. AGING, Avril 2013, Vol. 5 No 4.
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.
Peyrol et al, 2017. Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders. Nutrients 2017, 9, 306.
Singh AP, Singh R, Verma SS, Rai V, Kaschula CH, Maiti P, Gupta SC. Health benefits of resveratrol: Evidence from clinical studies. Med Res Rev. 2019 Sep;39(5):1851-1891. doi: 10.1002/med.21565. Epub 2019 Feb 11. PMID: 30741437.