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How a Sedentary Lifestyle Depletes NAD+ and Why it Matters

Caitlin Beale, MS, RDN

It's well understood that a sedentary lifestyle isn't great for our long-term health, especially when it comes to the aging process. Regular physical activity has many benefits, from reducing the risk of chronic diseases to improving mental health and cognitive function. One reason may be related to nicotinamide adenine dinucleotide (NAD+)

NAD+ is a molecule found in all living cells. Research connects low NAD+ levels to accelerated aging, as it's involved in vital cellular processes like DNA repair and energy production.

NAD+ levels naturally decline with age, but a sedentary lifestyle can speed up this process. On the other hand, research suggests that regular physical activity may help preserve NAD+ levels, an essential part of the equation for healthy aging.

Why Are Healthy NAD+ Levels Essential for Health?

Before exploring the connection between NAD+ and sedentary lifestyles, it helps to understand the overall importance of this molecule. NAD+ is a cellular coenzyme found in nearly every cell in your body. A coenzyme is a small molecule that helps an enzyme do its job.

NAD+ protects against oxidative damage, facilitates energy metabolism in the mitochondria (tiny organelles responsible for energy production inside each of your cells), and contributes to healthy aging. Without NAD+, your cells couldn’t generate the energy that’s crucial for healthy mitochondrial function.

Your body makes NAD+ from vitamin B3 we consume through food, and as you age, the NAD+ pool decreases. Your body also uses NAD+ to help your cells respond to stress (which is part of the reason that stress depletes it), as discussed in a review from Signal Transduction and Targeted Therapy.

While aging and health conditions related to aging are complex subjects, mitochondrial function and NAD+ levels definitively play an important role. A review in Nature explains that NAD+ depletion is a central mechanism of age-related functional and health conditions like frailty, and neurodegeneration.

Luckily, you can help protect your NAD+ levels with smart diet and lifestyle choices. Let's explore how regular physical activity may help keep this critical molecule at healthy levels as you age.

What's the Relationship Between Physical Activity and NAD+ Levels?

Your muscles need energy from mitochondria to function, but first, mitochondria need NAD+ to generate ATP, the primary form of energy for your cells. According to a review from Skeletal Muscle, NAD+ is vital for healthy muscle.

Physical activity appears to increase NAD+ levels, while a sedentary lifestyle depletes NAD+, as noted in a study published in Nature Aging. Researchers examined 52 people divided between young and older adults. Older adults were separated into three groups: trained, normal, and  impaired. Their NAD+ was measured along with many other metabolites.

NAD+ was significantly lower in older participants, and the least active participants also had the lowest levels of NAD+. Young adults also tended to have higher NAD+ levels than older adults. Interestingly, younger participants in the study had similar NAD+ levels as the most active older participants (those who engaged in 3 or more hours of activity each week). 

Mitochondrial health and muscle function were positively associated with higher NAD+ levels, suggesting the impact of physical activity. NAD+ levels were also higher for those with more average steps per day. In other words, the more someone moved each day, the higher the NAD+ levels.

This is only one study, so more research is needed. Still, it provides a glimpse into just how important physical activity may be for preserving NAD+ levels as we age.

How Does a Sedentary Lifestyle Deplete NAD+?

The impact of a sedentary lifestyle on NAD+ isn't fully understood, and it's likely complex. Research hypothesizes that it may be partly due to a rate-limiting step in the pathway that generates NAD+ in your muscle cells.

The enzyme nicotinamide phosphoribosyltransferase (NAMPT) helps to create NAD+. NAMPT is found in mitochondria, and according to a study from the American Journal of Physiology, Endocrinology and Metabolism, levels of NAMPT are lower in people who are sedentary.

NAMPT also decreases with age, but physical activity can increase it, according to a study published in Physiological Reports. In this study, both young and older adults who participated in 12 weeks of aerobic and resistance exercise increased their NAMPT levels—with older adults seeing more significant improvements. 

The researchers conclude that this is one reason why exercise is so essential for improving the loss of muscle function associated with age.

A Sedentary Lifestyle Accelerates the Aging Process

Since we know that NAD+ naturally drops with age, the combination of decreased physical activity as we get older is a recipe for an accelerated aging process.

A sedentary lifestyle contributes to weaker bones and sarcopenia. Sarcopenia is the loss of muscle mass and strength that can occur with aging. Some muscle loss is considered a normal part of the aging process, but it can be accelerated by lack of exercise and poor nutrition. 

The result is a decreased quality of life, frailty, lack of mobility, and an increased risk of falls and fractures, which only advances the aging process. But it doesn't have to be this way. Exercise is considered one of the most effective ways to prevent or reverse sarcopenia. 

According to an animal study published in Cell Death and Disease, mitochondrial dysfunction is also linked to sarcopenia. A study in Nature Communications took muscle biopsies from older adult men and found that those with sarcopenia had lower mitochondrial activity and low  NAD+ levels. 

So staying active to support muscle mass and mitochondrial health by increasing NAD+ levels could be one way to maintain healthy mobility and keep sarcopenia at bay.

Staying Active Raises NAD+

Physical activity strengthens muscles and encourages NAD+ generation to keep levels up, supporting muscle health and all your cells. As mentioned earlier, the study published in Nature Aging found that NAD+ significantly dropped with age, but those who were the most active had the highest NAD+ levels regardless of how old they were.

That study also showed that oxidative stress appeared to increase with reduced activity and age but was significantly lower for those who exercised more. Oxidative stress is one of the leading underlying causes of aging. It occurs when there is an imbalance between the production of free radicals and the body's ability to neutralize them.

Over time, this imbalance can damage cells and tissue, leading to visible signs of aging. Additionally, oxidative stress has been linked to chronic diseases usually associated with aging, such as heart disease, cancer, and Alzheimer's. NAD+ also helps to protect cells against oxidative stress, according to a review in Redox Report.

So, while we can't stop the aging process, we may be able to slow it down by being physically active and keeping NAD+ levels high.

Supplementing with an NAD+ Precursor Can Add Another Layer of Support

Successful aging takes a multi-faceted approach beyond physical activity. Diet, sleep, and stress management all play a role. And while we can't turn back the hands of time, supplementing with NAD+ precursors can be an additional tool to support cellular health.

NAD+ precursors are molecules that the body can convert into NAD+. Studies show that supplementing with precursors helps your body generate more NAD+. A study published in Scientific Reports concluded that supplementation with nicotinamide riboside (NR) effectively increases NAD+ levels in the body.

A mouse study published in Cell Metabolism also found that supplementing with NR helped support muscle strength and endurance, likely by supporting mitochondrial health. In humans, NR supplements could decrease oxidative stress and may enhance physical performance in older adults, according to a study from the European Journal of Nutrition.

NAD+ precursors are also linked to positive changes in other aspects of healthy aging, including brain health, cardiovascular protection, insulin sensitivity, and other markers of metabolic health, according to a review in Cell Metabolism.

There's no doubt that a sedentary lifestyle is a risk factor for aging, but there are ways to offset that damage. Increasing NAD+ levels with supplements like NR may help protect against some of the adverse effects of a sedentary lifestyle and support healthy aging.

Key Takeaways: Physical Activity Is a Vital Component of Healthy Aging

A sedentary lifestyle lowers NAD+ levels, alters mitochondrial health, and contributes to aging, but you can counteract these effects by regularly moving your body.

NAD+ precursors may also help, and have been linked to positive changes in other aspects of healthy aging and other markers of metabolic health. 

In combination with increased physical activity and other healthy lifestyle habits, NAD+ precursors like Tru Niagen® could offer a simple yet effective way to fight back against the effects of aging and improve the quality of life as we grow older.

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