As we age, our DNA accrues damage. The fragile nucleic acids that structure DNA are highly sensitive to sunlight, inflammation, and other factors that come along with living life. Because of this, all organisms feature DNA repair machinery.[*]
That’s where NAD+ comes in. This industrious molecule is a repair crew, an energy maker, and a longevity activator all in one. And so, if you’re interested in healthy aging, it’s wise to familiarize yourself with NAD+.
NAD+ and Aging
Unfortunately, as we age, NAD+ levels fall. In fact, by middle age NAD+ levels have plummeted to half that of our youth.[*]) Why? Because:
- We make less of it
- We use more of it (we require lots of NAD+ to repair age-related DNA damage)
- More of it gets destroyed (thanks to an enzyme called CD38 that “gobbles up” NAD+ at an accelerated rate as we age)[*]
This decline, research suggests, does not help us age gracefully.[*] Aging is marked by genomic instability, mitochondrial dysfunction, and various functional declines linked to NAD+ depletion. But there’s good news. Replenishing NAD+ levels “may slow or may even reverse some aspects of aging,” according to a 2018 paper in Translational Medicine of Aging.[*]
The last decade of NAD+ research has been exciting. For instance, researchers have shown that NAD+ replenishment increases lifespan in yeast, worms, and rodents.[*] More recently, noted Harvard researcher David Sinclair (and colleagues) published a 2023 study suggesting that restoring NAD+ levels with the NAD+ precursor, nicotinamide mononucleotide (NMN), improves biomarkers of cardiometabolic health in middle-aged and older adults.[*] Read on to learn more about the science behind NAD+ along with natural ways to support NAD+ levels.
What is NAD+?
NAD+ (nicotinamide adenine dinucleotide) is a molecule—a co-factor—that facilitates chemical reactions in your body. These reactions support the function of the nutrient-sensing pathways mTor and AMPK, which influence metabolism, repair, and aging itself. NAD+ also regulates a group of proteins called sirtuins crucial for DNA expression.
NAD+ is so essential to life that it’s found in all living cells. Let’s review its primary functions.
DNA Repair
NAD+ supports DNA repair by activating an enzyme called PARP-1. The activation of PARP-1 is one of the main drivers of NAD+ depletion. For example, the activation of PARP-1 to repair skin sensitive to UV light depletes significant amounts of NAD+.[*]
Mitochondrial Health
Mitochondria create energy for your cells. But as we age, these power plants start to sputter.
Enter NAD+. Researchers found that supplementing old mice with the NAD+ precursor NMN, reversed age-related mitochondrial declines in various tissues of the mice, revitalizing youthful-functioning mitochondria.
Energy Metabolism
NAD+ accepts and donates electrons to turn glucose and fatty acids into ATP.[*] (It helps turn food into energy.) These “redox reactions” are essential to life.
Sirtuin Activation
If you’ve dabbled in longevity research, you’ve probably heard of longevity genes. These enzymes, also called sirtuins, are central to aging and regulate the sleep-wake cycle among other things.
Researchers have shown that supplementing mice with “sirtuin activators” (like NAD+ precursors and resveratrol) have improved endurance, organ function, and overall longevity.[*]
Something to note: higher NAD+ levels appear to help activate sirtuins, triggering DNA repair and other beneficial processes.[*] With lower NAD+ levels, sirtuins stay switched off and you lose all of those anti-aging benefits.
4 Ways To Replenish NAD+ Naturally
For best results, take a holistic approach to NAD+ repletion. Consider supplements like NMN—yes—but don’t neglect lifestyle factors like exercise, fasting, and sun protection.
#1 Exercise
Exercise keeps you young. It keeps you strong and functional while reducing the risk for most chronic diseases.[*]
NAD+ may be part of this story. Exercise supports NAD+ levels by increasing the activity of the NAD-synthesis enzyme, nicotinamide phosphoribosyltransferase (NAMPT.)[*]
And it’s a significant increase. A 2019 paper in Physiological Reports found that aerobic and strength exercise increased NAMPT levels in adults over 55 by 28 and 30 percent respectively.[*]
#2 Fasting and calorie restriction
Your NAD+ production system is continuously monitoring your energy supply. When energy levels are low—such as when you haven’t eaten much—NAD+ production ramps up.
This extra NAD+ activates sirtuins and puts your body into “repair mode.” [*] In repair mode, cells clean themselves via autophagy and mitophagy, and PARP-1 restores damaged DNA.
Calorie restriction can kick off this system, but be mindful not to overdo it. The dangers of chronic undereating—muscle loss, bone density issues, fatigue—are no joke.
A safer strategy is temporarily restricting calories with intermittent fasting (IF). There’s still a danger of undereating, but IF is more about limiting when vs. how much you eat.
#3 Curtail DNA-damaging activities
Anything that damages DNA will deplete NAD+. And though you can’t stop all age-related DNA damage, you can avoid the big offenders.
Take sun exposure, for instance. Some sun exposure is healthy, as it helps you synthesize vitamin D—but too much UV light damages skin and sucks up considerable amounts of NAD+.
#4 Support methylation
Methylation means adding methyl groups to DNA, proteins, or other molecules. This process influences many biochemical systems and functions in the body.
One of these systems is NAD+ production. Healthy methylation helps you recycle NAD+ (i.e., keep levels higher) through the aptly-named “salvage pathway.” [*]
A fundamental way to support methylation is to ensure you get enough methyl factors like B12, riboflavin, and TMG.
What about supplementing NAD+?
First of all, consuming NAD+ itself in traditional supplement form doesn’t effectively replenish NAD+ levels due to the molecule’s propensity to break down in the gut. And while niacin (vitamin B3) is an essential nutrient and an NAD+ precursor, it’s an inefficient NAD+ supplement due to its inability to be absorbed intact..[*] Not to mention, high doses of niacin have the unfortunate side effect of causing a ruby-red face, better known as niacin flush.
Let’s discuss NR and NMN because they’re the two primary NAD+ replenishment supplements on offer. Research suggests that both may support healthy cellular NAD+ levels.[*][*] NR and NMN dance together. When NR enters cells, an enzyme called nicotinamide riboside kinase converts it to NMN. In other words, NMN (also found in many foods) is a more direct precursor to NAD+ than NR.
NMN can also enter cells directly via a dedicated transporter called Slc12a8. This 2019 discovery shook up the world of aging research.[*]
There’s plenty of preclinical evidence on NMN supporting the restoration of NAD+ levels and slowing aging in animals.[*] And clinical studies are trickling in (like the previously mentioned Sinclair study) that suggest NMN supplementation supports the replenishment of NAD+ and may support metabolic health in humans.[*][*][*] Taking a high-absorption NMN supplement may be a smart addition to your holistic NAD+ regimen.
