NAD+ is an enzyme aid that triggers cellular energy production for every living cell in your body. NAD+ primarily functions in our cell’s mitochondria, often nicknamed ”the powerhouse of the cell,” but it’s importance in our bodies was further highlighted by a group of scientists in Australia.

 Hassina Massudi and a team of researchers from the University of New South Wales discovered that maintaining levels of NAD+ may play a role in aging. 

 The team drew their conclusions from studying NAD’s role in fueling the mechanisms needed to combat oxidative stress, a significant contributor to age-associated changes in the body. 

What is oxidative stress?

 Our mitochondria convert food into cellular energy but produce a terrible byproduct in its manufacturing process called free radicals. Free radicals can cause cellular damage, wreaking havoc on our cellular function.

Usually, our bodies have a healthy amount of antioxidants to combat the problem, keeping a delicate equilibrium of free radicals and antioxidants. 

However, sometimes, we demand a little more energy from our bodies. We may overexert ourselves, kicking our mitochondria into overdrive. This overproduction of energy shifts the balance of our free radicals to an unmanageable level, known as oxidative stress.

Factors like intense exercise, lack of exercise, sleep deprivation, poor diet, drinking, smoking, and viral infections all lead to oxidative stress.

How does oxidative stress connect to aging?

 In 1954, biochemist Dr. Denham Harman proposed the “Free Radical Theory of Aging,” hypothesizing that people age because of the imbalance of free radicals due to their role in damaging proteins, cell membranes, and DNA.

But later, in 2018, physiologist Dr. José Viña and his colleagues unveiled “A Free Radical Theory of Frailty,” arguing that free radicals do not necessarily dictate how long we live. Instead, Viña hypothesized the excess in free radicals causes frailty in older people, leading to a decline in their overall quality of life. 

Whichever theory posits our understanding in the future, scientists universally agree that an excess of free radicals is a detriment to one’s health. And perhaps Viña’s approach more so questions how we define aging. Maintaining our wellbeing as we age is just as much a human desire as lengthening our lifespan.

Excitingly, the research from Massudi and the team in New South Wales shows a strong connection between the presence of NAD+ and oxidative stress, thus underlining NAD’s importance on how we age.

The study design.

The study obtained human skin samples from consenting patients scheduled for surgery at the Sydney Adventist Hospital in Australia. Participants included patients aged between 15-77 and newborn babies. 

 Researchers removed skin tissue from non-sun exposed areas of the pelvic region to study the least environmentally affected samples from their subjects.

 The study monitored the following in correspondence with NAD+ to assess if NAD+ levels are linked to age-associated changes in our body:

1. Lipid peroxidation

 Lipid peroxidation is a form of oxidative stress, specifically the degradation of lipids in our cell membranes. 

2. Oxidative DNA damage

DNA is also vulnerable to oxidative stress. If the damage is left unfixed, our bodies can trigger cell death or mutagenesis, a process in which alters our genetic information. 

3. PARP activity

 PARPs or Poly (ADP-ribose) polymerase are a family of proteins involved in DNA repair, genomic stability, and programmed cell death.

4. Sirtuin 1 activity

 Sirtuins, specifically SIRT1, are a class of proteins involved in regulating the cell.

The study results.

• NAD+ levels declined with age in both males and females.

• Lipid oxidation increased with age in males.

• DNA damage correlated strongly with age in both males and females. 

• PARP activity significantly increased with age in males but was less evident in females.

• SIRT1 activity negatively correlated with age in males.

Building on the study of aging.

 The study developed by Massudi and the team provides quantitative evidence that the depletion of NAD+ may play a significant role in the aging process by limiting energy production, DNA repair, and genomic signaling. 

 Further study in the potential of boosting NAD+ with supplements or by natural means could unlock more curious findings. Already paving the road, a paper published in the Translational Medicine of Aging shows the therapeutic potential of boosting NAD+ as we age. 

Whether solving the puzzle of oxidative stress will lead to a longer lifespan or better quality of life as we age, continued NAD+ research may redefine the boundaries of the aging process.

Your body wants to follow an evolutionary blueprint. Instinct says, “Rise with the sun. Sleep when it sets.” 

A circadian rhythm refers to an internal clock that influences the pacing and patterns of biological systems. Organs lull or stimulate function in response to environmental changes. 

This phenomenon may be most noticeable as a “sleep-wake” pattern. However, the average work schedule does not always allow your body to adhere to its circadian rhythms. 

Sleep deprivation is an inevitable cellular stressor. When your cells are stressed by an exhausted body, they are more susceptible to damage.

Even occasional sleep deprivation can lead to health complications down the road.

Sleep deprivation contributes to major health conditions.

Sleep is an essential component of cellular function and long-term health. Humans need rest and your system struggles to repair in moments of high activity. 

A preclinical study from the University of Rochester Medical Center shows that immune cells called microglia “repair and rewire” the brain during sleep. 

Microglia fight infection and repair cellular damage to the brain. They also influence neuroplasticity, or the way the brain absorbs and stores information. 

Poor sleep denies cells the opportunity to heal the body. This may be why chronic insomniacs are more susceptible to strokes. 

In 2019 the American Academy of Neurology published a ten-year clinical study conducted on a subject base of 487,200. Participants were asked if they experienced symptoms of insomnia at least three nights per week. Nearly one quarter reported sleep issues. 

Over the course of the trial, there were “130,032 cases of stroke, heart attack, and other similar diseases.” The study found that insomniacs were 18% more likely to experience cardiovascular or cerebrovascular disease. 

Better sleep is good for your brain.

Brain cells ultimately dictate your every move. The brain needs sleep for short-term functioning and long-term health. The relationship between cell damage and sleep deprivation is particularly evident in its impact on cognition.

Multiple clinical studies demonstrate that extreme cases of sleep deprivation can result in mania and psychosis. A trial published in Frontiers in Psychiatry suggests auditory and visual hallucinations often occur after three or four days without sleep.

Cellular activity and circadian rhythms are inextricably linked. Preclinical research from the University of Pennsylvania School of Medicine shows that brain-cell housekeeping occurs during sleep and “may also be involved in regulating” circadian rhythms.

Mitochondrial dysfunction and sleep.

But what’s actually happening in the cell? One of the impacted functions occurs within our mitochondria. 

Mitochondria are the powerhouses of the cell. They supply cells with energy, and that energy powers the roles they play in your body. 

Within the mitochondria, our energy production relies on a small coenzyme called NAD+. NAD+ is an essential resource your mitochondria need to activate their “power factories”. They provide the “fuel” that ignites the turbines within the mitochondria.

However, when your body’s cells are under stress, they may focus their energy on combating the stressor. This reduces your available supply of NAD+.

Example: You stay up all night binging your favorite show. The next day, cells work overtime to carry you through the day, depleting their supply of NAD+. 

Sleep deprivation is a major stressor that wreaks havoc on cells and may even cause mitochondrial dysfunction. Preclinical research published in the journal Cellular Metabolism suggests that mitochondrial function falters when one’s circadian clock is compromised. 

Impaired mitochondria struggle to fuse and duplicate, thus impacting the maintenance of various organ systems. Without the cellular energy mitochondria provide, organs struggle to perform their most basic functions. 

Prioritize sleep for your cells.

Cellular health can be challenging to observe, yet it has an undeniable influence on your overall health. Cells rely on a consistent circadian rhythm to prevent illness and good mitochondrial function is a vital component of that process. 

Stressors are an inevitable part of modern life. Understanding your cellular needs is the first step in improving your cellular health. And good sleep reinforces your cells’ ability to maintain and protect your most vital organs.

Put devices down an hour before bed. Following a consistent sleep schedule safeguards your health in the long-term and at the cellular level.

NAD+ (nicotinamide adenine dinucleotide) supports a vast range of functions within the human body. NAD+ is a vital component in energy generation. Known commonly as a “coenzyme,” NAD+ works with enzymes to support mitochondrial function. 

Mitochondria power your cellular turbines. Think of this organelle as a battery that lives within every cell, powering each cell’s many functions.

Mitochondria use NAD+ to convert sugars, fats, and proteins into the cellular energy we know as adenosine triphosphate or ATP. Muscles use ATP to power voluntary and involuntary movement within the body.

But to understand how NAD+ aids muscle function, you must first understand the way muscles behave.

NAD+ is essential for muscle function and movement.

A recently published study in Skeletal Muscle suggests muscles that support your mobility, like skeletal and cardiac muscles, tend to be “energetically expensive.”

Therefore, movement itself ends up requiring a larger amount of NAD+ relative to “stationary” tissues. A solitary muscle cell often requires thousands of mitochondria to operate, further proving the importance of NAD+ in movement. 

The human body has evolved to meet the needs of its various organ systems. As a result, NAD+ is hyper present in muscle cells, and other metabolically active tissues, due to the high number of mitochondria. 

How do muscles work?

Muscles perform unique patterns of contraction and relaxation to help the human body function. The involuntary movement supports bodily mechanisms beyond your conscious control. 

Cardiac muscles create a heartbeat through repeated, involuntary contraction. And while you can breathe with intention, muscles help your lungs breathe independently, even while you sleep.

Alternatively, voluntary muscle function supports any movement dependent on conscious choice. 

From stretching to walking, muscles help you navigate your world. Skeletal muscles, which wrap around your bones, are particularly influenced by voluntary movement. 

Your hands cannot operate without your instruction. When you run, your intention drives the speed and intensity of movement in your legs. 

All these motions rely on NAD+ to convert macronutrients into ATP, which in turn fuels the contractions.

How are muscle repair and NAD+ connected?

Muscle repair is largely coordinated by nutrient availability, which is particularly necessary during and after exercise.

NAD+ is not just responsible for cells’ utilization of energy. A 2017 review published in Antioxidants and Redox Signaling demonstrates that NAD+ provides cells with key information about nutrient levels, playing a vital role in communicating cellular needs.

NAD+ helps facilitate the conversion of nutrients into energy and is an essential cofactor for cellular repair enzymes. This process ultimately supports muscular regeneration. 

Mature muscle cells exhibit signs of high plasticity and can reach full regeneration after an injury.

Muscles are not impervious to damage. Both over-training and inactivity can threaten their structural integrity and health. 

To put this in the simplest terms, NAD+ helps muscle cells repair and recover.

The stages of muscle repair.

A recent review published by Thomas Laumonier and Jacques Menetrey has revealed that muscular repair is a three-stage process: destruction, repair, and remodeling.

Destruction phase:

The destruction phase begins immediately following an injury. After a muscle ruptures or tears, the wounded area fills with blood. 

Inflammatory cells flock to the injury, using the blood as its main conduit. Cells centralize inflammatory and healing responses around the injured tissue, protecting any healthy adjacent cells from destruction.

Repair phase:

After inflammatory cells complete the destruction phase, repair begins—vital cells called macrophages clear any remaining cellular debris. 

Macrophages are responsible for removing dead cells and leftover dried blood from the injury site, paving the way for muscle stem cells called satellite cells to begin healing.

Satellite cells band together to create new muscle fibers, while cells called fibroblasts create a bridge of connective tissue over the torn muscle.

According to a review published in the International Journal of Molecular Sciences, NAD-dependent enzymes called sirtuins are also critical for muscle repair. In response to physical stimulation, sirtuins activate and trigger mitochondrial biogenesis, the process of cellular reproduction.

Remodeling phase:

As satellite cells and fibroblasts mature, they transform into scar tissue. 

While scar tissue eventually fully transitions into muscle, its formation from the repair phase is structurally different from muscle itself. 

Physical therapy and careful movement can help correct these differences. Bodywork can help detangle clumps of scar tissue to help it align with the stripe-like structure of healthy muscle. 

All these cells depend on energy from their mitochondria to facilitate these three stages. A clinical study published in Muscle, Ligaments, and Tendons Journal showed that the severity of a muscular injury determines the energy and time needed to heal.

Remodeling is the primary mechanism that supports the growth of muscle mass, according to a review published in Antioxidants and Redox Signaling.

As you exercise, macrophages, satellite cells, and fibroblasts undergo the same repair process at a smaller scale. Without a large tear to heal, new tissue mimics the parallel structure of existing muscle fibers, creating bigger and stronger muscles.

Rest builds muscle.

Muscle function and the availability of NAD+ follow an energetic pattern known as circadian rhythm. The circadian rhythm controls sleep-wake cycles and “is involved in many important aspects of muscle physiology,” according to a review recently published from F1000 Research.

Rest is essential for repair, especially for muscles. It allows your body to repair any site of injury, without risking further, energy-draining damage.

Mindful exercise, paired with plenty of rest, builds healthy, energized muscles. Listen to your body and create an intuitive exercise regimen that benefits your health in the future.