By Grace Alano

Grace Alano

A scientific breakdown of the body's cell signaling process and the Protandim® family of products are changing the conversation on healthy aging.

Question: Do you need a brain to be intelligent?

It seems straightforward, right? But think about it. Think about a plant – it doesn’t have a brain. However, its roots know how to grow down into the soil and the leaves know how to grow up the harnessed energy from the sun. Sunflowers follow the sun through the course of the day and reset themselves at night so that they are ready to follow the sun again in the morning. Some plants like the Venus Flytrap can even outsmart and feed on organisms with primitive brains. 

Think about ants and spiders. Some ants can actually farm. It’s true. While spiders spin a new web every morning – a place where they hunt, store their food, and call home.

These are incredibly complex behaviors from organisms you probably consider primitive. But how do they do this? Why do fish swim in schools? Why do baby ducks follow their mothers? Why do dogs fetch?  Bacteria are the most successful organisms on Earth. How do they know how to grow, divide, and look for food? Are they thinking about this?

From single-celled organisms all the way up to humans, it begs the question: is intelligence sitting in that three-pound (1400 gram) organ called a brain? Or is there something else going on? 

Is a brain required for all that intelligent behavior we can see going on around us?


Cellular intelligence living within our DNA and genes

You don’t actually think about the blood flowing through your veins, nerve impulses, breathing, or digesting the breakfast you had this morning. If you workout in the morning, you don’t have to think about your muscles repairing themselves or bones becoming stronger. All of this just happens. 

Take the skin for example. Let’s say you cut your finger – the wound healing process that goes on behind the scenes is an incredibly organized process. It starts with the immune system, removing all that damaged tissue. Then, the skin cells have to grow and divide in order to replace the damaged and missing tissue. Ultimately your finger becomes as good as new. It’s amazing because it all happens without you having to think about it.

This all happens because of the highly coordinated cellular intelligence your cells possess. But where does this intelligence live with your cells? It lives inside our DNA and genes.

To clear up some terminology, the sum of your genetic material is called DNA–a vast network of information storage that trumps any digital storage technology available today. In fact, technology companies are now discovering ways to store data in DNA.

Then DNA is divided up into discrete segments called genes. A gene is a specific information for the cell to make something specific. So, you can think of DNA as being the “parts list” for the cell and the gene being the instructions for a specific part or protein. To put this into perspective, think about this. Your DNA is made up of about 30,000 genes.

Because the job of DNA and its genes is to store information, it’s passive. It just sits there ready to convey information to the cell. Think of DNA as a complex blueprint for a house. That blueprint can’t swing a hammer and build a house by itself. It needs someone to actually do the work. Within our cells, those workers are called proteins, or enzymes, that do all the labor-intensive stuff to make sure our cells function properly every second of every day. 

And like any good construction crew, the blueprint and workers also need a good foreman. Someone who passes along the orders and makes sure things happen. In the scientific world, the foreman is called cellular signaling. 

Cell signaling unlocks and coordinates cellular intelligence

When anything happens within your body, it’s due to a chain reaction. A signal is passed from the cell to the genes, and voila. Enzymes get to work. How that signal gets through the cell is an incredibly complex process, it’s always a chain reaction that we call coordinated cellular signaling. 

But what initiates cellular signaling? Great question. 

Receptors do. Think of receptors as little sensors that sit on the outside of the cell and sometimes float around inside of the cell. These sensing proteins initiate cellular signaling working a lot like a lock and key. The key, in this case, is a signaling molecule that – through some complex chemistry – fits perfectly within the receptor and unlocks or initiates the receptor, and triggers the cell signaling chain reaction. 

Much like a chain of dominos, a small signal can activate a cell signaling pathway that ultimately triggers a massive event within our cells. Normally this is called your metabolism or physiology.

But whatever you call it, cell signaling ultimately controls everything that happens within your cells and throughout your body.

And is what gives every cell in your body its cellular intelligence.

Nutrigenomics and the discovery that nutrients could activate health-promoting genes

When researchers discovered that dark chocolate had cardiovascular health benefits, they began to investigate exactly why. But after breaking the compounds down in dark chocolate, these researchers learned that those healthy compounds that had such a positive impact on health were actually only available in trace amounts. It didn’t make sense. Moreover, when they gave these compounds to people, they were poorly absorbed by the body and metabolized very quickly. They also found that these compounds couldn’t even make it into the cell. 

However, after further experiments, they discovered that they were actually binding to a receptor molecule and activating a cellular signaling pathway. These compounds and a receptor molecule created a massive ripple effect throughout the body that you can enjoy every time you indulge in some dark chocolate. This is exactly nutrigenomics–nutrition working through cell signaling to support the natural process of turning on our genes. Simple, right? 

LifeVantage is utilizing nutrigenomics to support healthy aging

LifeVantage is using the same process to take on one of life’s biggest mysteries…the normal aging process.

The Normal Aging Process

Aging is a complex process driven by diverse changes in genetic, molecular, biochemical, and cellular events. This multifactorial process is ultimately characterized by a gradual decline in physiological functions, which ultimately compromises the ability of an organism to survive with increasing age.

There are currently many different theories as to why we age. Some estimates put the number of theories of aging above 300 from damaged-based theories to we are programmed to age theories, to loss of cellular communication theories, to psychosocial theories, to biochemical, molecular, and cellular theories of aging.

However, no one theory of aging can account for all the changes known to occur with age. What is more likely the case is that all of these different theories of aging are having an additive effect all contributing to the normal declines known to occur with age.

More recently a new theory of aging has emerged that seems to encompass many of the biochemical, molecular, and cellular theories of aging. The so-called “loss of stress response theory of aging.” The loss of stress response theory of aging states that when a young individual to literally any type of stress it can successfully sense and respond to that stress much better than its older counterparts. To date, it is the best, single, unifying theory of aging seems to encompass many of the changes known to occur. At the core of this response are cellular signaling pathways.

Biochemical, molecular, and cellular theories of aging: The oxidative stress theory of aging, the mitochondrial theory of aging, and the sirtuin theory of aging

To help you live as healthy for as long as possible, it is important to understand the major theories of aging and how it is possible to use nutrigenomics to target them

The approach at LifeVantage is to bring together the most well known and researched theories of aging and create products that specifically target the root causes behind them. As such, there are three that we focus on.

The Three Most Studied Theories of Aging

To date, there are currently three theories of aging that have been the most extensively studied:

  1. The oxidative stress theory of aging
  2. The mitochondrial theory of aging
  3. The sirtuin theory of aging

While seemingly disjointed, all three of these theories of aging have a cellular signaling component. However, as we age, these signaling pathways both fail to react to their respective stimuli and their responses are attenuated relative to their younger counterparts. 

Oxidative Stress Theory of Aging and the Nrf2 Pathway

The oxidative stress theory of aging states that as we age we start to accumulate free radicals and other oxidants. If left unchecked, this oxidative stress can go on to have very serious consequences to the cell. Oxidative stress can ultimately lead to oxidative damage by attacking and damaging essential biological structures of the cell and ultimately compromises cellular function.

Antioxidants are the cell’s primary defense against free radicals and other oxidants. There are two major classes of antioxidants: 1) dietary antioxidants obtained through food and nutritional supplements and 2) endogenous antioxidants produced by the body.

It has long been debated which class of antioxidants is more important in human health. However, a recent review of the scientific literature led by the United States National Institutes of Health’s National Center for Complementary and Integrative Health concluded: “Rigorous trials of antioxidant supplements in large numbers of people have not found that high doses of antioxidant supplements prevent disease1.” Thus, much attention has shifted to the body’s endogenous antioxidant and detoxification systems.

Endogenous antioxidants are antioxidants made by the body and are the primary line of defense against oxidative stress. In general, endogenous antioxidants either prevent oxidants from being formed, or remove. Endogenous antioxidants form a complex network of antioxidant metabolites and enzymes. These networks work together, throughout the cell, to neutralize oxidants and protect important biological structures from oxidative damage.

These intertwined and highly integrated networks most frequently garner their reducing equivalents from cellular energy production that are passed throughout the network. One major advantage of these antioxidant systems have is that they can redox cycle. Whereas most dietary antioxidants can only be used once and destroyed, endogenous antioxidants can neutralize numerous oxidants because they are constantly being regenerated back to their active or reduced state.

Endogenous antioxidants can also be upregulated in times of increasing oxidative stress. The primary pathway responsible for upregulating endogenous antioxidants and other detoxification pathways is the Nrf2 cellular signaling pathway. Under times of normal, or low oxidative stress, Nrf2 is normally found anchored to another protein in the cell membrane called KEAP1. Under times of oxidative stress, oxidants and other electrophiles release Nrf2 from KEAP1. Nrf2 then translocates to the nucleus where it binds to its specific promoter sequence to ultimately activate its target antioxidant and other detoxification genes.

However, with age, the activity of this Nrf2 cellular signaling pathway has been shown to decrease–both in its ability to sense oxidative threats and ultimately upregulate its target genes.

LifeVantage’s Protandim® Nrf2 Synergizer™ was specifically formulated to target the Nrf2 pathway. In a recent scientific study conducted by LifeVantage two health-promoting genes, NQO1 and HMOX1, known to be activated by Nrf2 were examined. What was found was that this formula was indeed able to activate these genes. It was shown that in just 24 hours there was a 40 percent increase in NQO1 and a 51 percent increase in HMOX1.* 

Thus, Protandim Nrf2 Synergizer was indeed able to activate the cell’s own antioxidant and detoxification defenses.

What does turning on the Nrf2 pathway do?

  • Supports the body’s natural detoxification processes*
  • Reduces oxidative stress by 40% in 30 days*
  • Significantly reduces cellular stress through Nrf2 activation*
  • Produces enzymes capable of neutralizing more than 1,000,000 free radicals*
  • Helps to regulate survival genes*
  • Supports the natural cellular repair and rejuvenation processes* 

Mitochondrial Theory of Aging and the NRF1 pathway

Another major theory of aging is the mitochondrial theory of aging. The mitochondria are essential for cellular function. It is estimated that about 95% of the energy we need to function every second of every day, is produced by the mitochondria. The mitochondria produce energy by breaking down the food we eat and capturing high-energy electrons in the process.

When mitochondria are functioning properly, they harness the energy of these electrons to produce energy for the cell. At the end of this process, the mitochondria attach these electrons to molecular oxygen that ultimately get detoxified to water. However, this process isn’t 100 percent efficient. Even in young, healthy mitochondria, electrons can escape this process potentially forming free radicals and other oxidants. 

The mitochondrial theory of aging states that as we age, our mitochondria don’t work as efficiently.  As the mitochondria age they don’t produce as much energy and also produce more free radicals and other oxidants. The reduction in energy production compromises cellular function. The increase in free radicals and other oxidants in turn damage structures of the cell including the mitochondria. This mitochondrial damage goes on to further compromise mitochondrial function leading to a vicious downward spiral of even less mitochondrial efficiency and more free radical and oxidant production ultimately contributing to an increase in the overall cellular burden of oxidative stress.

There have been a number of nutrients shown to support mitochondrial health. These nutrients include alpha-lipoic acid, acetyl-L-carnitine, and coenzyme Q10. Alpha-lipoic acid is both fat- and water-soluble. It has 400 times the antioxidant power of vitamin E and C combined and shown to neutralize oxidants that damage mitochondria, can recycle other antioxidants, and regenerates glutathione. Acetyl-L-carnitine is an amino acid naturally produced in your body that helps generate energy. It is responsible for transporting fatty acids into the mitochondria where they are utilized for energy. Coenzyme Q10 is a fat-soluble antioxidant concentrated in the mitochondria. It is essential to shuttle electrons through the electron transport chain and ultimately in the production of ATP. 

A major cellular signaling pathway involved mitochondrial health is NRF1 (nuclear factor erythroid 2-related factor 1). The NRF1 cellular signaling pathway, directly or indirectly, regulates a number of genes involved in mitochondrial health, turnover, and biogenesis. These include another protein named Nrf1 (Nuclear respiratory factor-1). Nrf1 activates the expression of key genes involved in metabolism, cellular growth, energy production, and mitochondrial DNA transcription and replication. Together with Nrf2, Nrf1 also provides the essential function of coordinating gene expression between nuclear and mitochondrial genomes. An additional protein shown to support mitochondrial health is PGC1-alpha (peroxisome proliferator-activated receptor gamma coactivator-1-alpha). PGC1-alpha is a transcriptional coactivator that regulates genes involved in energy metabolism. It is the master regulator of mitochondrial biogenesis and turnover and also healthy blood pressure and cholesterol levels.

LifeVantage’s Protandim® NRF1 Synergizer™ was specifically formulated to target the NRF1 pathway and provide nutrients shown to support mitochondrial health. In a recent scientific study conducted by LifeVantage two mitochondrial health-promoting genes, Nrf1 and PGC1-alpha, known to be activated by NRF1 were examined. What was found was that this formula was indeed able to activate these genes. It was shown that in just 24 hours there was a 65 percent increase in NRF1 and a 71 percent increase in PGC1-alpha.* 

Thus, Protandim NRF1 Synergizer was indeed able to activate the cell’s own mitochondrial health-promoting genes.*

What does turning on the NRF1 pathway do?

  • Improves cellular performance through energy function* 
  • Enhances cellular health* 
  • Allows cells to function at peak performance*
  • Increases cellular energy (ATP)*

Sirtuin Theory of Aging and the NAD Pathway

Another major theory of aging is the sirtuin theory of aging. This theory came out of studies examining the health benefits of caloric restriction. Caloric restriction is the process whereby caloric intake is restricted by as much as 40 to 60 percent. In numerous experimental models, animals put on calorically restricted diets experienced significant increases in maximum lifespan by as much as 60 percent. It was ultimately determined that the family of proteins called the “sirtuins” were absolutely required to experience the increase in lifespan brought on by caloric restriction.

When the physiology of humans undergoing caloric restriction was examined, a number of health benefits were discovered. Humans undergoing caloric restriction experienced benefits in cardiovascular health, weight management, reproductive health, sleep, and cognitive function. 

As researchers began to understand the molecular biology of these sirtuins, they found that the enzymatic activity for most of them required the molecule NAD+ (nicotinamide adenine dinucleotide). NAD+ is an essential molecule for many biochemical reactions, most notably metabolism of the food for energy.

NAD+ coexists in cells in two forms: 1) a molecule called NAD+ and 2) a molecule called NADH. It turns out, it is the ratio of these two forms of NAD+ (the so-called NAD+/NADH ratio) that is important for controlling a number of other cellular signaling pathways. Under normal conditions, the cell very tightly regulates the NAD+/NADH ratio. However, changes in your metabolism like long- or short-term caloric restriction can change this ratio. As the ratio of NAD+/NADH changes (NAD+ levels increase), this means there is proportionately more NAD+ floating around the cell than NADH. This is biologically important because an increase in NAD+ has been shown to activate several key enzymes, including sirtuins.

Recently, much attention has been paid to the NAD+ biosynthetic pathway asking the question, is it possible to increase NAD+ levels in the cell outside extreme caloric restriction?

NAD+ is made in two ways through the NAD+ biosynthetic pathway: 1) the de novo and 2) the salvage pathways. 

In humans, de novo synthesis of NAD involves the amino acid, tryptophan. Quinolinic acid is generated directly from tryptophan. The quinolinic acid is then converted to nicotinic acid mononucleotide (NaMN) by transfer of a phosphoribose moiety. An adenylate moiety is then transferred to form nicotinic acid adenine dinucleotide (NaAD). Finally, the nicotinic acid moiety in NaAD is amidated to nicotinamide (Nam), ultimately forming nicotinamide adenine dinucleotide.

The salvage pathway in humans involves the recycling individual components of NAD+ containing a pyridine base. The three vitamin precursors used in these salvage metabolic pathways are nicotinic acid (NA), nicotinamide (Nam) and nicotinamide riboside (NR). These compounds can be taken up from the diet and/or produced within cells and by digestion of cellular NAD+ and are termed vitamin B3 (niacin) or NR. These precursors can take up extracellular NAD+ from their surroundings and both nicotinamide and nicotinamide riboside can be absorbed from the gut.

Despite the presence of the de novo pathway, the salvage reactions are essential in humans and thus more important. This high requirement for NAD+ results from the constant consumption of the NAD+ in reactions such as posttranslational modifications, including those by sirtuins.

LifeVantage’s Protandim® NAD Synergizer™ was specifically formulated to target the the most important genes in the NAD biosynthetic pathway. In a recent scientific study conducted by LifeVantage two NAD synthesizing genes were examined, NAMPT and NMNAT1. What was found was that this formula was indeed able to active these genes. It was shown that in just 24 hours there was a 12 percent increase in both of these genes. *

Thus, Protandim NAD Synergizer was indeed able to activate genes the most important genes in the NAD biosynthetic pathway.*

We were also curious about the competition who took the opposite approach. Instead of using nutrigenomics, other companies are trying to create sirtuin activity from scratch. Using this method, their products only show a 2 percent increase in sirtuin activity. 

What does activating the NAD pathway do?

  • Improves mental focus and concentration* 
  • Supports positive mood and motivation*
  • Boosts mental and physical energy* 
  • Supports the body’s healthy inflammation response*
  • Maintains cholesterol levels already within the healthy range*
  • Supports a healthy vascular system* 

The Protandim family of products work synergistically to further activate these same genes*

After discovering how well the three products in the Protandim family were working individually, LifeVantage wanted to know if there was a cumulative, synergistic positive effect when all three products were given together.

The results exceeded our expectations: 

Tri-Synergizer effect on Nrf2 Genes

When taken together, there was a 78 percent increase in the NQO1 gene responsible for fighting oxidative stress and detoxifying the body. There was also a 848 percent increase in HMOX1 for healthy inflammatory response. Together, these results show a further 83 percent and 1563 percent synergistic increase in NQO1 and HMOX1, respectively.* 

Tri-Synergizer effect on NRF1 Genes 

When taken together, there was a 90 percent increase in the Nrf1 gene responsible for overall cellular and mitochondrial health. There was also a 120 percent increase in PGC1-alpha–the gene responsible for mitochondrial turnover and biogenesis. Together, these results show a further 38 percent and 69 percent synergistic increase in Nrf1 and PGC1-alpha, respectively.* 

Tri-Synergizer effect on NAD Genes 

When taken together, there was a 128 percent increase in the NAMPT gene–a key enzyme in the NAD recycling pathway. There was also a 227 percent increase in NMNAT1 – the central enzyme for NAD synthesis. Together, these results show a further 967 percent and 1792 percent synergistic increase in NAMPT and NMNAT1, respectively.* 

Nutrigenomics. A different approach to health with better results. 

The true genius behind nutrigenomics lies, perhaps, in its untouched potential. The great news is that we’ve barely scratched the surface. The truly exciting news? Our products are just going to become exponentially better and more effective over the next decade. 

Alone, Protandim NRF1, Nrf2, and now NAD Synergizers are each incredibly powerful, effective solutions. They’re helping our cells do some amazing things. But the magic we’re now seeing is the cumulative impact that happens when the entire Protandim family works together. The Tri-Synergizer isn’t just meeting our best-case scenarios in the lab – it’s far exceeding them. In the process, Tri-Synergizer is giving us a glimpse into both the incredible potential of Nutrigenomics, LifeVantage as a company, and what we can offer the world.*

* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.