Age-Related Muscle Loss: How NAD+ Helps Preserve Lean Mass

In this article:

  • Why you might experience muscle loss as you age and how it could impact strength and physical function.
  • How nicotinamide adenine dinucleotide (NAD+) supports aging muscle health at a cellular level, from enhancing mitochondrial function to activating sirtuins.
  • What human and animal studies show about the effects of NAD+ precursors on muscle function. 
  • How you can optimize your NAD+ protocol to support muscle health and what to consider when it comes to the dose, timing, and specific precursor you choose.
  • Why it’s important to combine NAD+ support with a strength training program and balanced diet.

Getting older doesn't have to mean giving up strength or stamina. In fact, new research shows that NAD+ might help protect against muscle loss with aging, thanks to its ability to support muscle energy and repair. (1) By keeping NAD+ levels steady over time, you may be able to help your muscles bounce back faster and stay stronger, even as the years roll on. Whether you're going for a scenic hike, hitting the gym, or even just chasing your grandkids around the yard, NAD+ support can help you stay active and energized.

Read on for everything you need to know about how NAD+ can help combat age-related muscle loss, including how it works, what the science shows, and how you can optimize your protocol.

Understanding Age-Related Muscle Changes

As you get older, your body undergoes a series of changes, including a gradual loss of strength and muscle mass. Starting around age 30, muscle mass declines at a rate of about 3-8% per decade, which accelerates even more after age 65. (2, 3) Maintaining muscle isn't just about looking fit. In fact, sarcopenia (aka muscle loss) can take a toll on almost every aspect of life, from upping the risk of falls and fractures to making it harder to stay active and independent. (4)

While many people often turn to standard approaches like protein shakes or strength training, these strategies alone aren't always enough. Some research suggests that aging muscles may actually respond differently to diet and exercise than younger muscle cells, which might require more targeted interventions to support muscle building and healthy aging. (5)

The Cellular Mechanisms of Muscle Aging

If you want to stay strong as you age, understanding the cellular side of muscle maintenance is a smart place to start. Here's what's really going on behind the scenes as your muscles age.

Mitochondrial Function Changes in Aging Muscle

Over time, the mitochondria in your muscle cells become less efficient, which can impact energy production and muscle endurance. This decline in mitochondrial efficiency is closely linked to lower levels of NAD+, making it harder for the muscle cells to convert nutrients into energy your body can use. Not only can this impact muscle protein synthesis, which helps build muscle, but it can also contribute to muscle loss, weakness, and slower recovery. This highlights the importance of protecting mitochondrial health for preventing age-related muscle loss. (6, 7)

Protein Synthesis vs. Degradation Balance

As you age, the balance between building and breaking down muscle protein shifts, tipping towards more muscle breakdown and less muscle growth. This is partly due to a decline in mammalian target of rapamycin (mTOR) pathway signaling, leading to less muscle protein synthesis. (8) At the same time, proteasome activity and autophagy (both of which help clear out damaged proteins) can go into overdrive, speeding up muscle loss in the process. (9, 10) NAD+ plays a central role in maintaining this delicate balance by supporting the energy needs of protein turnover and regulating these pathways. For this reason, keeping NAD+ levels stable could be key to preserving muscle mass and strength as you get older. (7)

Satellite Cell Function and Muscle Regeneration

Satellite cells are a type of stem cell found in the muscles, which are responsible for muscle repair and regeneration. As you get older, the function of these cells starts to slowly decline, making it much harder for your muscles to recover from injury or adapt to stress. Satellite cells also become less abundant and responsive over time, which can take a toll on your body's ability to build or maintain muscle mass. (11) NAD+ helps power the repair processes for your muscles by activating satellite cells and providing the fuel they need. On the other hand, when NAD+ levels drop, it makes it much harder for your muscles to rebuild and recover, leading to a loss of strength. (12)

NAD+ Mechanisms in Muscle Support

Curious how NAD+ supplementation for muscle preservation actually works? Before we dive into the benefits, let's break down the science behind NAD+ for lean mass preservation.

Sirtuin Activation and Muscle Metabolism

Sirtuins (a type of signaling protein involved in regulating metabolism) help keep your muscles healthy by creating new mitochondria, which generate energy for the cells. Sirtuins like SIRT1 and SIRT3 depend on NAD+ to operate and regulate the mix of muscle fibers in your body, maintaining a careful balance between those geared for endurance or strength. (13) Plus, they also fend off oxidative stress, a common culprit of inflammation and tissue damage as you get older. (14) Together, NAD+ and sirtuins work hand-in-hand to support long-term muscle energy, resilience, and overall health. (15)

Enhanced Mitochondrial Function

NAD+ plays a key role in supporting the mitochondria, which churn out the energy your muscles need to move. With improved mitochondrial function, your muscles are also able to perform more effectively and better handle calcium, which regulates muscle contractions. (16) As an added bonus, NAD+ also helps defend the muscles against oxidative stress, which can build up over time and wear down strength. (17) The result? Better strength support and muscles that recover faster and stay even more resilient as you age.

Neuromuscular Junction Support

While your brain might call the shots, it's the neuromuscular junction (aka the connection between the muscles and nerves) that actually makes movements happen. (18) Over time, these connections weaken, leading to slower, less coordinated muscle function. (19)

That's where NAD+ comes into the picture. It maintains motor unit function and supports muscle innervation, making sure your muscles stay properly "plugged in" by helping your nerves transmit signals that tell the muscle fibers to contract or relax. (20) With better neuromuscular health and communication, your muscles can respond faster and more efficiently to help you stay strong.

Research Evidence for NAD+ in Muscle Health

Wondering how all of this translates to the real world? Below, we take a closer look at the effects of NAD+ on muscle loss and aging, including what studies in humans and animals show and how NAD+ works alongside exercise to promote muscle health.

Human Studies on NAD+ Precursors and Muscle

Researchers are just starting to connect the dots between age-related muscle changes, NAD+ support, and improved muscle health in humans. Here's what the science shows so far:

  • In a 2024 meta-analysis, researchers concluded that nicotinamide mononucleotide (NMN) could help enhance muscle function in middle-aged and older adults, even at small doses. (21)
  • In one study, taking 250 milligrams (mg) of NMN daily for 6 or 12 weeks led to improvements in gait speed and grip strength, two common markers of age-related muscle dysfunction. (22)
  • A study in twins found that supplementing with 250-1,000 mg of nicotinamide riboside (NR) per day boosted NAD+ metabolism, increased muscle mitochondrial numbers, and enhanced muscle stem cell function after five months. On the other hand, it didn't have any impact on metabolic health or body fat. (23)

Keep in mind that the science is still catching up, and not all studies have shown benefits across the board when it comes to muscle aging and NAD+ support. (24, 25) Not only that, but results can also vary depending on a long list of factors, like the type of supplement, dosage, and specific study population. Regardless, the research is still pretty promising, pointing to possible benefits for strength, endurance, and muscle function with age.

Animal Model Research

Research has turned up encouraging results for lean muscle maintenance through NAD+ support in aging animals. Here are a few of the highlights:

  • In one animal model, short-term supplementation with NR increased levels of NAD+, helped mice run longer and stay more active, and even prevented declines in grip strength. (26)
  • A year-long animal model study conducted in mice found that supplementing with NMN helped slow signs of age-related decline, including changes in mitochondrial function, energy metabolism, and physical activity levels. (27)
  • In mice, combining NR with aerobic exercise enhanced endurance, increased muscle mitochondrial proteins, and bumped up the amount of type I muscle fibers, which support endurance. (28)

But even though early evidence is exciting, translating results from animal models to humans isn't always simple or straightforward. More research is needed to understand the complex connection between muscle mass decline and NAD+ benefits in humans.

How NAD+ Works Alongside Exercise

NAD+ can support mitochondrial function and muscle repair at a cellular level, which could complement the gains you get from hitting the gym. In fact, studies show that exercise and NAD+ may actually work best together. For instance, one study in amateur runners found that NMN could increase aerobic capacity during exercise training by improving the skeletal muscle's ability to use oxygen. (29) Not only that, but coupling NAD+ precursors with protein might also be beneficial by boosting muscle protein synthesis, offsetting muscle damage, and promoting post-workout recovery. (30)

Of course, NAD+ isn't a magic bullet for muscle health and shouldn't be used as a substitute for tried-and-true interventions, like diet and exercise. However, NAD+ precursors can be a valuable addition to your muscle maintenance plan to help protect against muscle loss as you age.

Optimizing NAD+ Protocols for Muscle Support

If you're interested in preventing age-related muscle loss with NAD+ supplements, figuring out the right dose to fit your needs is key. While NAD+ precursors like NMN and NR are often used in doses ranging from 100 mg to 1,000 mg per day, the right amount for you can vary based on your age, activity level, and where you're starting from. (31) A common starting point is around 250 mg per day, which you can adjust over time based on how your body responds. (22, 23)

Timing matters too, especially when it comes to building muscle. Pairing NAD+ supplements with protein-packed meals or taking them close to when you workout can tap into your body's natural muscle-building windows to help boost recovery. On the other hand, some people prefer to take NAD+ supplements right when they wake up to align with their circadian rhythm and increase energy levels during the day. (32)

Finally, keep in mind that NAD+ supplements aren't one-size-fits-all. NR tends to shine when it comes to enhancing endurance or mitochondrial function, whereas NMN might be a better bet if you're focused on improving muscle metabolism or insulin sensitivity. (33) Meanwhile, trigonelline (another NAD+ precursor) has a unique affinity for muscle fiber, which may give it an added edge for supporting strength. (34) Research analyzing multiple NMN studies has shown that this precursor can effectively promote muscle function and improve metabolic markers in middle-aged and older populations. Understanding the differences between these precursors can help you fine-tune your protocol to match your specific goals, whether that means building strength, increasing endurance, or maintaining muscle fiber quality.

Combining NAD+ with Resistance Training

Pairing NAD+ with strength training can unlock even greater benefits for muscle strength and stamina. Here's what you need to know.

Exercise-NAD+ Synergy Mechanisms

Resistance training doesn't just build muscle; it also kicks your NAD+ pathways into high gear to help fuel muscle repair and energy production. (35) For this reason, taking NAD+ precursors around your workouts may offer an extra edge, making it easier for your muscles to adapt and grow even stronger. Coupling NAD+ with exercise could even accelerate muscle recovery and amplify performance, helping you get the most out of every workout.

Progressive Training Considerations

Any time you start a new strength training program, it's important to start slow and gradually progress as you go. Especially for older adults, easing into new exercise routines with proper form and manageable weights can reduce the risk of injury and give your muscles plenty of time to adapt. (36) NAD+ can also provide an added layer of support, helping to enhance recovery and increase muscle energy. (17, 37)

Be sure to keep tabs on your progress by tracking changes in strength, endurance, and overall muscle function. This can help you tailor your exercise program to your specific needs and ensure safe, steady progress toward better muscle health.

Nutritional Strategies to Support NAD+ Muscle Benefits

Pairing NAD+ support with a solid nutrition plan is a smart way to maximize the potential muscle-building benefits. Aim for around 1.4-2 grams of protein per kilogram of body weight daily, depending on your age and activity level, and focus on foods rich in leucine (like eggs and dairy), especially before or after your workout. (30, 38) While some people prefer spreading their protein intake evenly throughout the day, some research shows that filling up on protein first thing in the morning and opting for a lighter dinner might actually help boost muscle growth even more. (39)

Of course, individual needs can vary, and older adults or those just getting back into the swing of things might benefit from slightly higher intakes or more frequent meals to support recovery and adaptation. Consider talking with a doctor or dietitian for more personalized guidance based on your individual needs.

Monitoring Muscle Health Progress

Tracking your muscle health doesn't have to be complicated, but it definitely should be consistent. It's often helpful to measure simple metrics like endurance improvements, changes in body composition, or strength gains (like grip strength, number of reps, or the amount of weight you're able to lift), which can give you a clearer picture of your progress. For a deeper dive, some people also track biomarkers like creatine kinase or lactate dehydrogenase, which can provide a closer look at your progress and NAD+ effectiveness. (40, 41)

If you're not seeing results or have any concerns, check in with a healthcare provider. This is also a good idea if you're older or have any underlying health issues, as they can personalize your plan to fit your needs and help you make adjustments as needed.

Conclusion

Keeping your muscles strong and healthy as you get older isn't just about hitting the gym. In fact, giving your body the right cellular support is just as important. NAD+ precursors can be an effective addition to your muscle maintenance toolkit, especially when combined with regular resistance training, a balanced diet plan, and regular progress checks. Research on NAD+ transporters in the brain has revealed fascinating connections between central nervous system NAD+ levels and peripheral muscle health, suggesting that systemic NAD+ support may work through multiple pathways. But while early research in humans and animals has turned up some promising perks, it's not a one-size-fits-all solution, and more long-term, larger scale studies are still needed. Consider teaming up with a healthcare professional to personalize your plan and develop a strategy to help keep your muscles healthy as you age.

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Rachael Ajmera

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Rachael Ajmera is a registered dietitian and health writer with a passion for plant-based nutrition and exploring how diet and lifestyle shape health and longevity. She earned her undergraduate degree from the University of Central Missouri and holds a master’s degree in Clinical Nutrition from New York University.

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