At NOMON & Co., we review the latest research on aging every day, guided by our vision of building a society in which "productive aging" becomes the norm, and we continually look for findings that can be applied in everyday life. NMN (nicotinamide mononucleotide) is one of the nutrients that has drawn our attention in this search.
NMN is a direct precursor — the immediate building block — used by the body to synthesize NAD+, a molecule essential to human life. NAD+ is known to decline with age, and slowing this decline may offer a way to influence the aging process. Here we look at what NAD+ is and what positive effects raising NAD+ may have, drawing on research that also connects it to physical exercise.
What you'll learn in this article
- What NAD+ is, and why it declines with age
- How supplementing NAD+ precursors can positively change muscle
- How resistance training may help restore NAD+ in muscle
What Is NAD+?
NAD+ stands for nicotinamide adenine dinucleotide, and it is essential for life. NAD+ is used in the process of breaking down sugars to produce ATP.
- ATP
- the energy that all living organisms use to stay alive
It is also used in the process of repairing damaged genes.
NAMPT, the Enzyme Essential for Making NAD+
The enzyme that plays the most important role in producing NAD+ is called NAMPT2. NAMPT works in tissues throughout the body, including the brain, muscle, and digestive tract. However, NAMPT decreases with age, and the amount of NAD+ synthesized falls.
There is also an enzyme that breaks NAD+ down, called CD38. The activity of CD38 increases with age, so the level of NAD+ in the body declines, and this is thought to contribute to a decline in tissue function3.
Recent research suggests that suppressing the decline of NAD+ in various ways may help prevent the age-related decline in tissue function.
Supplementing NAD+ Precursors
As NAD+ declines with age, how to maintain it becomes an important question. Here we introduce a study in which niacin (nicotinic acid), one of the precursors of NAD+, was taken as a supplement4.
In this study, patients with mitochondrial disease were given 750–1000 mg/day of a niacin supplement for 10 months. At this dose, a side effect known as the niacin flush — reddening and flushing of the skin — occurs.
Patients with mitochondrial disease have abnormalities in their mitochondria, the site of energy production, and their NAD+ levels are lower than those of healthy individuals in both blood and muscle. After taking niacin, NAD+ levels rose 2.3-fold in muscle and 8.2-fold in blood.
Furthermore, alongside the increase in NAD+, muscle strength that had been reduced recovered — roughly 10-fold in the abdominal muscles, 2.5-fold in the upper arm, and 2-fold in the back. The number of mitochondria themselves also increased, suggesting that the rise in NAD+ led to greater energy-producing capacity.
Taken together, these results — from a study in patients with a mitochondrial disorder — suggest that increasing NAD+ enhances mitochondrial function in muscle, allowing more energy to be produced, which may in turn improve muscle strength.
Exercise and NAD+
Beyond supplementation, resistance training has also been reported to be effective at raising NAD+ in muscle5.
Resistance training is exercise that places relatively high loads on muscle using machines such as the leg press, bench press, and cable pulldown. In this study, 16 men and women around 59 years of age trained twice a week for 10 months, and changes in muscle strength and NAD+ levels were measured.
As a result, not only did thigh muscle mass and strength increase, but the NAD+ concentration in muscle roughly doubled compared with before training. With this increase, the muscle NAD+ levels of the middle-aged participants recovered to levels comparable to those of young university students. At the same time, the amount of the NAD+-synthesizing enzyme NAMPT increased by 15%, suggesting that exercise may raise NAMPT levels and thereby increase NAD+.
Closing Thoughts
NAD+ is needed both for glycolysis — the pathway by which muscle rapidly breaks down sugar to produce energy — and for the reaction that clears lactate, the substance associated with fatigue that is generated in that process.
The two studies introduced here suggest that exercise increases NAD+ in muscle, and that raising NAD+ may improve muscle performance.
The significance of resistance training may therefore lie not only in the quantitative change of "enlarging muscle," but in transforming muscle into tissue that can produce more NAD+ — potentially building stronger, higher-performing muscle.
References
- Yoshida et al. Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice. Cell Metabolism 2019, 30, 329-342e5. ↩
- Camacho-Pereira et al. CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism. Cell Metabolism 2017, 23, 1127-1139. ↩
- Pirinen et al. Niacin cures systemic NAD+ deficiency and improves muscle performance in adult-onset mitochondrial myopathy. Cell Metabolism 2020, 31, 1-13. ↩
- Lamb DA et al. Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle aged, overweight, untrained individuals. Aging 2020, 12, 9447-9460. ↩
