The science behind Longevity - A look at aging
Understanding Aging
One of the challenges for scientists in recent years has been gaining a clearer understanding of the fundamental biological changes that accompany aging. There is no single primary cause of aging or unified "theory of aging" that accounts for all the features of biological aging. Aging is not caused by just one type of cellular damage or by too little/too much of one molecule. Aging itself cannot be influenced simply by focusing on one thing.
Rather, it involves a multitude of factors that accelerate and/or decelerate biological processes later in life. Among the most common perspectives on aging are those related to free radicals, mitochondria, and gene expression (subcellular level), cellular senescence and stem cell perspectives (cellular level), and neuroendocrine and immune perspectives (systemic level). The aging process entails understanding the molecular, genetic, and cellular mechanisms that make aging a risk factor for the development of chronic diseases.
It is becoming evident that targeted focus on healthier aging will slow and/or reduce the incidence of many diseases and improve health.
Healthier Aging
Healthier aging = successful aging.
The concept of healthy and successful aging primarily focuses on living a longer, fulfilling, and healthy life. There are two fundamental mechanisms that demonstrably lead to healthier aging.
- Physical activity
- Caloric restriction (Intermittent fasting, time-restricted eating)
Both of these activities provide benefits for healthy aging. Their specific biological mechanisms cause dramatic changes in metabolic functions, cellular signaling, mitochondrial functions, and gene expression (how our cells express themselves).
Athletes can serve as an excellent example of gene expression. Comparing long-distance runners and bodybuilders, their gene expression will vary depending on their training. Endurance training and strength training activate and deactivate different genes. As a result, the body can adapt its responses to better suit specific habits and environmental challenges. It makes much more sense to activate and deactivate a set of genes that promote increased endurance in a runner or cyclist. In a regular gym-goer, it makes more sense to adjust gene expression to increase muscle size and strength (endurance is less important).
Each person is made up of trillions of cells. Each of these cells has many tasks, such as repairing damage, producing energy, fighting pathogens, and responding to hormonal signals. In these cells, millions of cellular processes occur every second, ensuring the functioning of the entire biological system. The human body is incredibly complex and comprehensive, constantly trying to adapt to external and internal changing conditions.
However, each cell has its lifespan, influenced by the interaction of genetic, environmental, behavioral, and social factors and lifestyle. These interactions and changes over time can cause excessive damage and premature cell death, leading to inadequate or excessive gene expression.
Cellular damage occurs one way or another because it is a normal part of metabolism. When we are younger, cells do a better job of repairing this damage. As we age, some damage cannot be repaired. When damaged cells replace themselves, the damage is transferred to new cells. This accumulated damage affects cell function, including their ability to self-repair. Therefore, healthier aging requires creating an internal "friendly" environment that allows cells to perform their best.
That is the goal that supports functional cellular mechanisms for proper metabolism, repair, and energy production.
Healthier aging does not necessarily mean longer lifespan, but rather "extending the part of life spent in health."
And that is our primary goal.
Science and Formulation
To date, science has uncovered several fundamental mechanisms of healthy aging. In formulating Longevity, we focused on these mechanisms and aimed to mimic this effect. Among other things, we targeted substances that mimic the effect of caloric restriction and exercise. Our goal was to incorporate some of the functional cellular benefits into the dietary supplement.
Don't worry! No pill can replace real physical activity and healthy habits. It doesn't mean you can stop moving and eat unhealthy foods. It means we designed this product to work synergistically with other healthy habits and support healthier aging.
Although there is no unified theory of aging, all perspectives on aging have one thing in common: cell damage and dysfunction are at the core of aging.
After all, when we talk about anything related to aging, we're actually talking about cellular degeneration. Many signs of aging are often symptoms of failing cellular mechanisms or mitochondrial damage. But... We cannot overlook gene expression either (think of athletes, for example). Dysfunction in gene expression can increase the accumulation of damage, and the accumulation of damage can disrupt gene expression. It's almost a devilish cycle that accelerates over time and causes more problems than the organism can repair.
The good news is that this cycle can be interrupted at several points, with functional support for one molecule, pathway, or process improving the others. Even better news is that we don't have to do just one thing. We can support many simultaneously, multiplying the benefits.
That's our comprehensive approach to healthy aging.
While the market is flooded with products targeting aging, they tend to focus more on some narrow aspect of cellular energy, repair, or metabolism. Our approach focuses on the entire system and on a wide range of processes needed to support healthier, more functional, and more efficient cells.
When our team formulated Longevity, we focused on strengthening a range of cellular biomolecules, pathways, and processes.
We tried to turn metaphorical small pieces into a grand work of healthy aging.
But which piece is the most important for cells to function at their highest level? The answer is NAD.
Let's start here.
Formation and Optimization of NAD+
NAD, or nicotinamide adenine dinucleotide, is a critical molecule for healthy aging. Numerous studies have shown that cellular levels of NAD decline during chronological aging.
By middle age, our NAD levels drop to half the level of our youth. This decline plays a crucial role in the development of metabolic dysfunctions and age-related diseases. Increasing NAD+ levels improves some metabolic functions, has the ability to reverse mitochondrial dysfunction, and extends lifespan.
-
It seems that there is a vicious cycle in which molecular mechanisms involved in the aging process, such as oxidative stress, DNA damage, and inflammation, lead to a decline in NAD in tissues, which subsequently worsens the processes that caused its decline in the first place. (Another devilish cycle.)
A very important piece of the puzzle of healthy aging is undoubtedly the formation of NAD+. This molecule is present in all living cells, so it's no surprise that many bodily functions can only operate in conjunction with NAD+.
Therefore, there are several ways and pathways in the body to produce NAD+.
By middle age, our NAD+ levels drop to half the level of our youth.
The most direct pathway to NAD+ formation is through a substance called NR (Nicotinamide Riboside). NR is metabolized in the body and converted into NAD+. Since NAD+ is such a crucial molecule for the body, there are other processes by which NAD+ is formed. It is synthesized via the De Novo pathway, which utilizes the amino acid L-Tryptophan, Preiss-Handler, and Salvage pathways using Niacin (vitamin B3). Various tissues in the body utilize these three pathways to meet the almost unceasing demand for NAD+.
Therefore, we formulated the composition with a view to supporting all three pathways.
When scientists investigated why NAD levels decline with age, they found an enzyme called CD38, whose levels increase during aging. This enzyme causes the breakdown of NAD. The good news is that CD38 can be slowed down. Apigenin and quercetin, substances found in fruits and vegetables, act as inhibitors of CD38 and thus slow down its activity. In this way, they increase and optimize the amount of NAD+ in the body.
The first piece in supporting cells against aging.
Formation and Optimization of NAD+
- NR
- L-Tryptophan
- Niacin (vitamin B3)
- Apigenin (CD38 enzyme inhibitor)
- Quercetin (CD38 enzyme inhibitor)
But let's go one step further.
Mitochondria and Energy Metabolism
Mitochondria are among the most important organelles in cells, participating in a wide range of processes crucial to cellular function.
The key function of mitochondria is to generate cellular energy. Mitochondria host the major processes that enable energy production from nutrients. This "cellular power plant" produces 99% of energy (in the form of ATP). Cellular metabolism converts carbohydrates, fats, and proteins into energy. Each of these macronutrients has its own cellular energy pathway (glycolysis, beta-oxidation, citric acid cycle, oxidative phosphorylation) where cellular energy production occurs. (All of these pathways depend on NAD).
However, they also need other substances (cofactors) to contribute to the production. Without them, energy production could not proceed. All B vitamins except folic acid are involved in at least one and often several steps of the cellular energy production system. Substances such as alpha-lipoic acid, cysteine, and CoQ10 also participate in energy production in one of the steps of metabolism or support mitochondrial health.
Supporting mitochondria, energy metabolism, and ATP production is another piece for healthy aging.
Support for Mitochondria and Energy Metabolism
- B vitamin complex
- Alpha-lipoic acid
- N-acetylcysteine
- CoQ10
Mitochondrial biogenesis
Mitochondrial biogenesis is an important cellular process that creates new mitochondria. One of the best physiological conditions that lead to an increase in mitochondrial mass (formation of new mitochondria) is physical activity. Endurance exercise stimulates molecular pathways (PGC-1α, PGC-1β, AMPK, CaMK, ERK1/2, p38MAPK and others) that are the basis of cellular processes supporting mitochondrial biogenesis. This important cellular process is essentially part of the adaptive cellular response to the metabolic demands of the organism. Simply put, it is an adaptation to increased energy expenditure.
-
These "sensors" for nutrient availability regulate energy balance and play key roles in stimulating fat burning and fatty acid oxidation. Cells thus compensate for increased energy demands.
This adaptive response leads to greater mitochondrial formation, thereby increasing the cell's capacity to produce ATP.
Healthier aging requires a comprehensive scientific approach focused on the interacting network of molecules, pathways, and processes that enable cells to perform at their best.
The quantity and functionality of mitochondria have a fundamental impact on aging manifestations. It is well known that mitochondria are particularly affected by diseases and contribute to the aging process itself. Aging is therefore accompanied by a decline in mitochondrial function, and this decline may also contribute to the decline in organ functions. (Another, already the third, devilish cycle.)
Not only mitochondrial health, but also mitochondrial biogenesis, is the answer to healthier aging.
When we mentioned earlier that Longevity mimics the effect of exercise, we specifically referred to mitochondrial biogenesis. Specifically, the molecular pathways that trigger mitochondrial biogenesis. Scientific studies confirm that certain substances and plant extracts have the ability to stimulate these pathways and contribute to mitochondrial biogenesis. Another piece in supporting a more robust aging system.
Mitochondrial biogenesis and stimulation of molecular pathways
- Gynostemma pentaphyllum extract
- Resveratrol
- Pterostilbene
- Rutin
- PQQ
- Apigenin
- Alpha-lipoic acid
- CoQ10
Closely related to metabolic regulators is another group of enzymes...
Increase in sirtuin activity (longevity genes)
Sirtuins (Silent information regulators), also sometimes referred to as longevity genes, are a group of enzymes that regulate a wide range of cellular processes, particularly those related to cellular energetics and homeostasis. It is assumed that sirtuins play a key role during the cellular response to various stresses (caloric restriction, ketogenic diet, exercise, sauna) and are crucial for cellular metabolism. Sirtuins adjust cellular metabolism based on nutrient availability and regulate many metabolic functions, including DNA repair, genome stability, inflammatory reactions, and mitochondrial functions. Sirtuins activate and deactivate many genes involved in health and lifespan extension.
Sirtuins, for example, regulate signaling pathways such as PGC-1α.
At this point, it should come as no surprise that a proper lifestyle, including physical activity and a healthy diet, can influence health through increased sirtuin activity.
Substances that act as sirtuin activators were another piece that contributed to our understanding of healthy aging.
Support for longevity gene activity (sirtuins)
- Resveratrol
- Pterostilbene
- Cocoa extract
- PQQ
- Quercetin
- Rutin
Support for antioxidant protection
Mitochondria, the main energy "powerhouses" in cells, produce reactive oxygen species (ROS) as a byproduct during energy production. ROS are often referred to as harmful molecules that cause aging and cell damage. Yes, if the amount of ROS is not kept in check, their effect damages cells and mitochondria, contributing to aging. Unhealthy lifestyle, lack of sleep, and stress seem to be risk factors contributing to excessive production of reactive oxygen species. However, ROS are also an important part of the body's signaling pathways. It is well researched that exercise-induced increase in ROS production in skeletal muscle plays a desired role in skeletal muscle adaptation to endurance training. Exercise contributes to the production of reactive oxygen species, but it is unlikely to result in a level of oxidative stress that is harmful to health. Exercise is thus a positive type of stress, which, not only through ROS, triggers healthy cellular and mitochondrial adaptations.
Therefore, our goal is not to prevent mitochondria from producing ROS or to try to suppress them with a large amount of antioxidants. A better approach is to help mitochondria help themselves. These substances support the body's own antioxidant processes, reactions, and the production of enzymes that the body uses to protect against reactive oxygen species.
Supporting Antioxidant Protection
- PQQ
- Quercetin
- Rutin
- Alpha-Lipoic Acid
- CoQ10
- Zinc Cellular Aging and Telomere Shortening Inhibition
As mentioned earlier, our cells adjust their behavior throughout life depending on the state of nutrients and stress (gene expression). When we are younger, our cells do a better job of repairing damage. With increasing age, this process weakens, and damage can be transferred to new cells. As cells continue to divide, the ends of DNA (telomeres) gradually shorten. When telomeres reach their critical length, genetic information is lost, which can trigger cell self-destruction. An enzyme called telomerase slows down this shortening and helps with the constant renewal of telomeres.
Gradual telomere shortening is considered one of the molecular mechanisms of organismal aging.
Telomere shortening also reduces sirtuin activity. Conversely, increasing sirtuin activity stabilizes telomeres and improves conditions dependent on telomerase.
As mentioned earlier, when we are younger, cells do a better job of repairing this damage. As we age, some damage remains unrepaired. When damaged cells replace themselves, the damage is transferred to new cells. This accumulated damage affects cell function, including their ability to repair themselves. If a sufficient number of cells are damaged, it reduces tissue performance, leading over time to visible and invisible aspects of unhealthy aging.
Thanks to longer and more stable telomeres, it is possible to prevent the mass aging of cells and prevent the onset of a variety of diseases.
Supporting Telomerase Against Telomere Shortening
- Centella Asiatica Extract
- Vitamin D3
- Selenium
- Vitamin B9 Senescent (Aging) Cells and Immunity Support
When cells reach a stage where they can no longer divide, they become senescent cells. These are normally destroyed through a programmed process called apoptosis and removed by the immune system. However, with age, the immune system weakens, and a growing number of senescent cells escape this process and begin to accumulate in all tissues of the body. Their presence causes many problems because they release pro-inflammatory substances that cause chronic inflammation and damage to surrounding healthy cells and tissues. This accelerates aging.
Just like all the biological systems described above are negatively affected by aging, our immune system also begins to weaken and fail in later life. As it turns out, senescent cells intensely interact with the immune system, and enhancing immune system performance appears to be a suitable long-term approach to dealing with senescent cells. Therefore, its support is the final piece in the whole picture of healthy aging.
Supporting the Immune System and Eliminating Senescent Cells
- Rutin
- Quercetin
- Vitamin D
- Zinc
- Selenium
- Cocoa Extract Healthy Aging Within Reach
You now know the mechanisms that guided us in formulating Longevity. Our goal was to focus on comprehensive support for the body and all its interacting molecules, signaling pathways, and processes that positively influence the fundamental cellular mechanisms of aging and are an important part of healthy and successful aging, allowing you to live life to the fullest.
P.S. And magnesium? It cannot be omitted.
There is another important cofactor for energy production, and that is magnesium. Good observation, it's not in the composition. And no, we didn't forget to incorporate it into the formulation. We are aware that this is a small gap in an otherwise completely complex product for healthy aging, but it has its reasons. One of them is that just 50 mg of elemental magnesium added to the composition requires about 350 mg of magnesium bisglycinate. Such an amount would already require consuming 5 capsules instead of the current 4. The second reason, and it's not a marketing gimmick (aging isn't interested in marketing), is that we already have a product with magnesium. The body needs more than 50 mg of elemental magnesium per day, so we have created our own formulation that contains 6 forms of magnesium for perfect absorption and saturation of every tissue in the body. We are firmly convinced that you will benefit from supplementing additional magnesium. Not only physically but also cognitively.