There appears to be a little-known incompatibility between longevity and growth (particularly muscle growth). In fact, beyond a certain point, one must choose between gaining muscle and living longer.
This principle caught our attention when we read the book by Doctors DiNicolantonio and Fung entitled “The Longevity Solution [1] “. Its back cover states that it ” gives us all the keys to increasing our longevity while remaining healthy and full of vitality “.
Let’s take a closer look at how the body’s growth functions (anabolism) do not contribute to longevity.
Why do we age?
It is worth remembering that many theories on the causes of aging coexist ( see this article on the mechanisms of aging ):
- The long-term effect of oxidation in our cells,
- Loss of mitochondrial function (which generates our energy),
- telomere shortening with errors in the replication of our cellular DNA,
- Protein glycation,
- cellular senescence,
- immune system failure
- decrease in hormone production,
- accumulation of toxins in the body
- epigenetic modifications…
All of this can be exacerbated by poor diet, a sedentary lifestyle, chronic stress, genetic predispositions, etc.
Metabolic pathways linked to aging and nutrient sensors
A metabolic pathway is a set of reactions in our body, centered on a particular function involving specific genes, hormones, and/or proteins (often enzymes).
Today, we know of several metabolic pathways particularly involved in the aging process. These include, in particular, four main pathways with somewhat technical names:
- mTOR pathway (mammalian Target Of Rapamycin)
- IGF (Insulin Growth Factor) pathway, one of the growth hormones
- Insulin pathway
- The AMPK (AMP-activated Protein Kinase) pathway is closely linked to cellular energy and, therefore, to mitochondrial function.
Our article, summarized from the aforementioned work, attempts to lift the veil on the role of these systems, which, depending on how they are stimulated, contribute either to the onset of degenerative diseases or to increased longevity.
On the other hand, in all animals, survival is linked to the presence of “nutrient sensors” and their close association with growth [2]. These sensors will sense the presence of certain nutrients in the body, such as glucose (sugar), proteins, certain amino acids, etc. Now, it turns out that the 4 metabolic pathways seen above are linked (directly or indirectly) to certain nutrient sensors.
Consequently, we will see that by intervening in diet, it is finally possible to act on these metabolic pathways, and therefore to influence longevity.
The insulin pathway
The metabolic pathway of insulin is the most well-known. The most important role of this hormone, produced by the pancreas, is to respond to the intake of carbohydrates (sugars) from food and to store some of the ingested glucose. However, insulin can also promote cell growth and division, at the expense of cell lifespan.
Thus, DiNicolantonio and Fung mention that adding glucose to the food of C. elegans worms shortens their lifespan [3]. This also explains why, when blood glucose levels drop rapidly, such as during fasting or calorie restriction, a lower insulin level limits growth but prolongs lifespan in several animal species.
The IGF1 pathway
IGF-1 (or Insulin Growth Factor) is a growth hormone very similar to insulin, which also plays a role in aging. This hormone is secreted by the liver after stimulation by growth hormone (GH), produced by the pituitary gland. It enters the bloodstream to stimulate cell proliferation. It is an anabolic hormone, particularly for the growth of bone and muscle cells.
In the study of the ” Laron dwarfs ” who suffer from neither cancer nor diabetes, this Ecuadorian tribe has particularly low IGF levels, which prevents the development of tumors (as well as their growth in size, of course).
DiNicolantino and Fung also report that mice with a genetic growth hormone deficiency live 40% longer. Dr. Henri Joyeux, in his lectures, also warns of the harmful role played by cow’s milk – and the growth hormones it contains today (epidermal, transformation, and growth hormones of insulin) – which are adapted to calves and not to humans [4] .
In humans, lower levels of pituitary growth hormone (GH) and IGF are associated with better health and a longer lifespan. Conversely, high levels of growth hormones lead to excessive absorption and production of proteins involved in the body’s growth processes (anabolism). This promotes age-related diseases.
The mTOR channel
mTOR, or ” mammalian Target of Rapamycin,” refers to an enzyme whose production depends on the gene of the same name. It exists in humans, animals, and microorganisms. This pathway regulates the growth and motility of our cells. According to DiNicolantonio and Fung, this “nutrient sensor” is sensitive to dietary proteins and amino acids.
However, excessive mTOR activity can decrease lifespan according to various studies.
Thus, a restriction in dietary protein that can help lower mTOR levels, thereby reducing growth processes, may improve longevity.
It is primarily in childhood that mTOR promotes growth and development, whereas later in life, excessive activity in this pathway can accelerate aging.
Drugs that block the mTOR pathway – such as rapamycin – can prolong the life of yeast, primarily due to their effect on autophagy. They effectively prevent the accumulation of damaged proteins (and certain “waste” and foreign substances) in our cells.
Rapamycin is also an anti-rejection drug used in organ transplantation and an anti-tumor drug. It was isolated from a bacterium ( Streptomyces hygroscopicus ) taken from a soil sample on Easter Island ( Rapa Nui in Polynesian), hence the name of this molecule.
Aspirin, curcumin, chili pepper (capsicaine), hibiscus, coenzyme Q10, resveratrol, and EGCG from green tea in particular, by inhibiting mTOR, would also promote a longer lifespan.
The AMPK route
AMPK ( adenosine monophosphate-activated protein kinase ) is widely involved in cellular homeostasis (the functions that keep our cells alive). It regulates energy production (ATP, by the mitochondria*) and also its consumption. When activated, it induces a decrease in cell growth.
A drop in glucose is one of the signals that stimulates AMPK, as is a decrease in energy production. Metformin, an anti-diabetic drug (in which anti-aging properties have been discovered in recent years), activates AMPK.
As with mTOR, certain natural substances such as resveratrol (grapes, wine), epigallocatechin gallate EGCG (green tea, dark chocolate) or capsaicin (peppers, turmeric, garlic), alpha-lipoic acid, coenzyme Q10,… act on AMPK in the direction of extending lifespan.
Spermidine is a dietary supplement, more specifically for the activation of AMPK (and it also has senolytic properties).
Also, a cucurbit plant, Gynestemma pentophyllum, would activate AMPK by accelerating metabolism. It would thus also have an effect against obesity [7].
Caloric restriction, and in particular protein restriction, activates AMPK by improving glucose uptake and increasing the synthesis of new mitochondria in our cells. Its activity is considered to be opposite to that of insulin and mTOR.
Metabolic pathways and aging
Numerous other enzymatic systems coexist in the human body (approximately one hundred thousand functional proteins coexist within our bodies). For example, among the most studied in relation to aging are: PGC1alpha, SIRT1, Nrf2, FOXO, Klotho…
Similarly, several other hormonal regulatory systems (including the renin-angiotensin system, for example) have repercussions on longevity and health. All of this is complex and often intertwined, which justifies a holistic approach to aging.
Protein restriction and fasting
Protein restriction, by decreasing mTOR activity and activating AMPK (among other things), could therefore extend lifespan. However, such a restriction could lead to muscle loss (sarcopenia) in older adults. It is therefore essential to proceed with caution and moderation (see this article on appropriate protein intake based on age and activity level).
In fact, in adults, when growth is no longer necessary, the enzymatic systems that promote it become potentially harmful to longevity. Fasting, therefore, could help regulate these systems and ensure a healthier lifespan.
The human body is designed to withstand periods of famine (where we live on our reserves) and abundance (where we store food) [5]. During a period of fasting, the body begins by eliminating aged, sclerotic, diseased, and tumorous cells.
Fasting, which includes protein deprivation, also induces a reduction in mTOR activity, prompting the body to autophagy (the recycling /cleaning of old compounds and deteriorated proteins in our cells), especially since, as a reminder, every minute 200 million cells are born and replace the old cells that die [6] ( see also stem cells and anti-aging ).
Finally, during fasting, insulin levels decrease, which leads to an increase in other hormones called “counter-regulatory hormones,” which are also beneficial for health and longevity. According to the authors, these hormones are so named because their action opposes that of insulin. When insulin decreases, these hormones increase.
The authors advocate the “intermittent fasting” 16/8, which consists of not eating for 16 hours (including sleep time) with an 8-hour window to eat ( see here the secrets of intermittent fasting ).
While insulin encourages the body to store glucose, counter-regulatory hormones, on the contrary, encourage its use. The authors give as examples adrenaline and noradrenaline (the two main ones), but also cortisol, the growth hormone… Their levels increase particularly with the activation of the sympathetic nervous system, for example, in the stress response, during which glucose is used to produce energy, to prepare the body for fight or flight.
The fact that growth hormone (GH) increases significantly during periods of fasting (a 24-hour fast doubles or triples its production) is not a problem. The authors explain that this surge in GH occurs during fasting without protein synthesis because insulin levels and mTOR activity are low. Thus, there is no actual growth occurring at the same time.
In the end, the authors provide scientific explanations for the positive and already observed effects of fasting, calorie restriction, and protein restriction, particularly through metabolic pathways related to aging.
A large part of the book is also devoted to the various foods essential for “healthy aging”. We will not list them here, but they promote, depending on the case, the inhibition of mTOR activity, insulin or IGF1, or even the stimulation of the AMPK pathway.
Age-related diseases and protein intake
The authors also point out that age-related diseases, such as Alzheimer’s disease, are characterized by an accumulation in the brain of certain proteins that block the transmission of vital signals.
Cancer is also the result of the proliferation of several compounds, including several types of proteins, confirming that many degenerative diseases are linked to a kind of “growth excess” promoted by large intakes of dietary amino acids.
The final chapter of DiNicolantonio and Fung’s book outlines 5 logical pillars of a “longevity solution”:
- Calorie restriction,
- The decrease in the activity of the mTOR pathway or proteins,
- the appeal of coffee, tea, and wine,
- The benefits of salt, sodium, and magnesium intake,
- Increasing the intake of natural and healthy fats.
This book offers an interesting perspective on the complex phenomena of aging and ways to limit them (or at least not accelerate them). It also challenges some common misconceptions and taboos in medicine.
A critical eye and a bit of perspective are still necessary, but this work reinforces our idea of ​​a comprehensive and not fixed approach to the fight against aging, or rather the fight against accelerated aging and/or aging linked to degenerative diseases.
There is already much to be done to help people stay healthy for a long time; immortality or longevity records are not, for us, an end in themselves.
