Understand the Major Mechanisms
of Cellular Decline

“Perhaps no other structure is so intimately and simultaneously connected to both the energy of youth and the decline of the old.” – Nuo Sun¹

The science on aging has now shown the pivotal role mitochondria play in healthy cellular function and identified this “powerhouse” of the cell as a central factor controlling how we age. A single cell can have hundreds or even thousands of mitochondria. Working inside individual cells throughout the body, mitochondria produce the life-sustaining energy powering everything we do daily, from moving to breathing to thinking.

An essential function of mitochondria is to convert nutrients from the food we eat and oxygen from the air we breathe into ATP (adenosine triphosphate) — what naturally fuels our cells day and night.² Each cell needs a sufficient number of healthy and fully functioning mitochondria so it can work at full capacity to meet ever-changing energy demands.

Once known only as energy producers, scientific insight into complex mechanisms within the mitochondria have transformed aging research. Our understanding of the pivotal role mitochondria play in the health of our cells after middle age has grown significantly. And, this has focused our attention on mitochondrial dysfunction as a key driver of accelerated cellular aging and Age-Associated Cellular Decline (AACD).³

Mitochondria are found in greater numbers in tissues and organs where energy needs are the highest such as your muscles, heart, brain, liver and kidneys.⁴ This is also why these organs are at greater risk of dysfunction and disease in older age as mitochondrial function declines.

The impact of mitochondrial dysfunction can be far-reaching, as mitochondria play an important role in nearly every aspect of cellular function. This includes those vital to providing efficient energy production, and influencing the pool of reactive oxygen species (ROS), toxic byproducts, and debris within cells.⁵

During the natural process of producing cellular energy, toxic byproducts and ROS are created and can begin to build up, especially if mitochondria are functioning with less efficiency. This accumulation results in mitochondrial damage and cellular damage when levels of protective glutathione and other antioxidant defenses are insufficient.

After middle age, declines in levels of glutathione and NAD+ (nicotinamide adenine dinucleotide) are likely and can impair healthy cellular functioning. NAD+ is a coenzyme essential to turn nutrients into energy and vital for mitochondrial energy production. The age-related decline of this helper molecule leads mitochondria to lose efficiency. This results in decreased cellular energy production and increased ROS.⁶

Once cellular levels of glutathione and NAD+ are no longer enough and the extent of mitochondrial dysfunction becomes too high, cellular functioning becomes impaired. The impairment of cellular functioning is slow and progressive. The impact on the body may only be noticed when it begins to affect our tissues and organs. This progressive deterioration can lead to a variety of dysfunction such as:^7-9

• Lack of motivation
• Decline in daily energy levels
• Poor exercise tolerance
• Muscular cellular strength and stamina decline

Over time, a noticeable loss of muscle strength and function and other signs of accelerated aging may happen. If these declines in functioning are not controlled, conditions such as sarcopenia (muscle loss) or cognitive diseases may develop.

In order to maintain efficient cellular energy production and healthy functioning, mitochondria are equipped with quality control mechanisms.¹⁰ Natural processes called mitophagy (removal of damaged mitochondria) and mitochondrial biogenesis (growth and division to create new ones) help to protect the mitochondria and cell from dysfunction.¹¹

However, these natural processes tend to decrease in older age and are weakened by oxidative stress and inflammation.¹² As these quality control mechanisms become less and less effective, errors begin to slip through. Because of this, poorly functioning mitochondria are able to survive and accumulate. The result is mitochondrial dysfunction and AACD.

As our understanding has grown of how mitochondrial dysfunction is a key driver of accelerated cellular aging, this insight has been transformed into research and innovative therapies targeting the mitochondria to support healthy cell function and improve AACD.1

Within the human body is an intricate and elaborate system essential to our health and survival. This system is, of course, our immune system. Made up of a vast network of cells, tissues, organs, and organ systems, the immune system is spread all throughout the body.

A healthy functioning immune system depends on the health of our cells and their ability to identify foreign invaders in the body and destroy them before they’re able to cause harm.

Central to cellular health and our immune system’s ability to fight off harmful foreign substances is the cellular antioxidant glutathione. Virtually every living cell within the body depends on glutathione’s protective and detoxifying nature to clean out and dispose of free radicals and metabolic waste buildup.¹

Glutathione is well-known as a master antioxidant within the body. And, recently, science has made new discoveries into how glutathione is also a key switch for energy metabolism within cells that controls the immune response.²

Now, more than ever, we understand how glutathione is required by the immune system to regulate the immune response and keep inflammation under control, and to protect cellular health by neutralizing harmful free radicals and reducing oxidative stress.^3,4

Glutathione exists in our cells in two forms — reduced (active form) and oxidized (inactive form). Healthy cells have a balance of about 10 to 1, reduced to oxidized glutathione. For the immune system to function at its best, immune cells need to sustain optimal levels of the reduced and active form of intracellular glutathione.⁵

The health of our immune cells depends on glutathione to both control their activity and to act as an antioxidant. Because our cells are constantly bombarded by free radicals, they need a robust defense system to be protected against this attack.

Glutathione defends our cells from becoming altered and damaged, which can otherwise lead to a weakened immune system, reduced resiliency and frailty. This can eventually cause a variety of illnesses and diseases and accelerated aging.

The overall function of the immune system is to prevent or limit infection. This is based on its ability to distinguish between healthy and unhealthy cells. Unhealthy cells may be the result of infection from viruses or cellular damage.

While incredibly complex, the immune system is based on a network of various types of cells circulating throughout the body or residing within the tissues. It’s composed of two forms of immunity: innate immunity, which we are born with, and adaptive immunity, which we acquire throughout our life.6

The main stages of the immune system’s response are:

• First, a toxin or foreign substance (antigen) is quickly detected by the cells of our innate immune system.
• Next, a rapid non-specific inflammatory response is triggered by the innate immune system to contain the infection.
• Then, if the innate immune response is insufficient to control the infection, the adaptive immune system steps in with the recruitment and activation of two types of white blood cells (lymphocytes) — T cells and B cells.
• T cells and B cells are vital to this part of the adaptive immune system response. They work to coordinate a highly specific response against millions of different antigens. ⁶

When a foreign substance triggers an adaptive immune response, T cells and B cells rapidly expand to effectively defend against the pathogen.⁶ This dramatic increase in metabolic activity requires the mitochondria (the powerhouse of the cell) to produce huge amounts of cellular energy (ATP).

The increased ATP production causes increased reactive oxygen species (ROS) production, which triggers glutathione to respond as a buffer against ROS to prevent cellular damage.⁷

When immune cells become overwhelmed by free radicals and ROS, glutathione levels are thrown off and can become insufficient to protect immune cells and defend the body against pathogens.⁸ As a result, we begin to experience a progressive loss of healthy cellular functioning and eventually, a decline in healthy immune functioning.⁹

The important role of glutathione in cellular health and healthy immune function is profound. Without a healthy and fully functioning immune system, we simply cannot maintain our health. As we age, these important mechanisms involved in healthy immune function decline if intervention measures are not taken.

The discovery of the expanded role of glutathione to support immune defenses, in addition to protecting our cellular health, offers a new perspective into targeted solutions to improve our body’s resilience and to combat the age-related decline of glutathione.²

The exciting and emerging science of cellular nutrition has opened the door to cellular nutrients. These cellular nutrients show promise for their ability to restore, renew and replenish natural cellular processes that decline with age and enhance healthy cellular functioning to support healthy aging.¹⁰

Glutathione is the one of the most powerful antioxidants naturally present in our cells.1 Known as a “master antioxidant," glutathione is essential for cellular protection from oxidative stress and damage, maintaining mitochondrial health and healthy immune function, especially after middle age.²

Our growing understanding of the importance of glutathione and the significant role it plays in cellular processes has the potential to transform our understanding of the mechanisms of aging.

As the most abundant antioxidant in our cells, glutathione is highly associated with health and longevity. An abundance of glutathione keeps oxidative stress tightly controlled by creating a strong natural defense against accelerated cellular aging and Age-Associated Cellular Decline (AACD).^3,4

Glutathione must be made inside our cells. This unique tripeptide molecule is made up of three amino acids — cysteine, glycine, and glutamic acid.² Each of these amino acids is required for the continuous and adequate production of glutathione for cellular protection.

Unfortunately, glutathione levels decline after middle age and the precursor amino acids cysteine and glycine become deficient in cells. Although the exact reason for deficiencies in these amino acids is unclear, it may be linked to altered protein metabolism as we age.² Because of the decline in glutathione levels, an imbalance is created between antioxidants and free radicals inside the cells, which can cause oxidative stress to build up and become damaging to cells and organs.¹

Lower levels of glutathione are associated with declines in mitochondrial function, cellular protection, detoxification, and immune function, as well as an increase in inflammation. This decline in healthy cellular function can lead to accelerated cellular aging, a decline in organ function, and the onset or progression of chronic health conditions. These conditions include diabetes, heart disease and neurodegenerative diseases.^3,5

The creation of energy (ATP) in our cells requires oxygen and involves a series of chemical reactions within our mitochondria — the “powerhouses” of the cell. These chemical reactions create oxidants and toxic byproducts, which induce oxidative stress. Over time, oxidative stress can cause damage to mitochondria, cells, tissues and eventually organs if left out of balance.

An effective way to control free radicals from the inside out and detoxify cells from accumulated waste is with glutathione. As glutathione actively neutralizes destructive free radicals, it helps safeguard each cell in your body, protecting against damage and accelerated cellular aging.⁴

When the building blocks of glutathione are in adequate supply, the cell makes just as much glutathione as it needs to support healthy cellular function. The ability of glutathione to recycle antioxidants is part of what makes it so important. Most antioxidants are no longer useful to us once they’ve neutralized free radicals. Glutathione not only recycles itself, it has the ability to recycle other antioxidants, such as vitamins C and E as well.¹

However, as we age and oxidative stress increases, it often becomes too much for the available glutathione to effectively control. When this happens, we experience a gradual decline in cellular protection, deterioration in our body’s natural defense system, and damage associated with accelerated cellular aging.

As our knowledge of glutathione and its impressive protective nature has expanded, we understand, now more than ever, glutathione’s profound role in promoting healthy aging. Correcting glutathione deficiency is a promising solution to regaining glutathione levels, restoring natural defenses, and supporting healthy cellular aging.⁴

One thing we all share is that as we grow older our bodies change, and some of these changes increase the potential for decline, illness, and disease. Although life expectancy has increased significantly over the past century, our healthspan has not been increasing to the same extent as our lifespan.¹ Our healthspan is simply the portion of life where good health is enjoyed.

Understanding the complex reasons for why and how we age has been a significant challenge for aging researchers. The popular and well-supported Hallmarks of Aging paper, written in 2013, proposed nine interconnected reasons why we age.²

Identifying these nine hallmarks gives us incredible insight into what damages our cells as we age. And, it’s now widely recognized that the underlying process of aging actually is the accumulation of cellular damage over time.³

The build-up of cellular damage is believed to be a major factor driving the functional declines we experience as we age. And the hallmarks of aging help to explain how these different types of cellular damage affect the way we age.

One of the main hallmarks of aging is damage to our DNA, known as genomic instability. Our genome is made up of DNA, which contains all of the genetic information that makes us who we are. Gradual damage to our DNA and faulty repair mechanisms allow errors to pass through and cellular damage to buildup over time. So, genomic instability is the result of the accumulation of genetic damage over the course of our lives.²

Damage to our DNA is a significant contributor to the other hallmarks of aging as well. For example, telomere shortening, mitochondrial DNA damage, and mitochondrial dysfunction are all related to cellular DNA damage.²

Throughout our lives, our cells are constantly exposed to both internal and external factors that cause cellular damage. It’s the accumulation of cellular damage that ultimately leads to age-related conditions and accelerated aging.⁴

There are many ways cells can become damaged. For example, the natural process of producing cellular energy (ATP) creates oxidative stress each day, which can lead to the buildup of free radicals and toxic waste in our cells. A small amount of oxidative stress is necessary and beneficial to help fight off pathogens. However, when free radicals are no longer balanced by cellular antioxidants, damage occurs as a result. Inflammation is another culprit contributing to cellular damage and has far-reaching negative effects when it becomes chronic. There are also environmental and lifestyle factors including ultraviolet rays, cigarette smoke, alcohol use, poor diet, and pollution that contribute to the accumulation of cellular damage over time.⁵ Together, these factors negatively affect our cells and eventually cause changes to their structure and function. These cellular changes can have a significant impact on the way we age. The constant exposure to these stressors causes damage to the lipids (fats), proteins, and DNA within our cells.

Together, these factors negatively affect our cells and eventually cause changes to their structure and function. These cellular changes can have a significant impact on the way we age. The constant exposure to these stressors causes damage to the lipids (fats), proteins, and DNA within our cells.

Healthy cellular functioning depends on processes such as DNA repair, natural cellular detox, and quality control mechanisms such as autophagy. However, when these repair processes become faulty, cellular damage continues to accumulate and eventually damages our tissues and organs, affecting their performance.⁴