You might not have heard of NAD+ until recently, but this molecule has been quietly keeping you alive since the day you were born. It’s involved in more than 500 enzymatic reactions in your body, playing a critical role in everything from energy production to DNA repair.
The problem is, NAD+ levels don’t stay constant. They decline as you age, and that decline has measurable consequences for how you feel, how you function, and how well your body resists disease.
Understanding what NAD+ does and why it decreases over time can help explain some of the changes you experience as you get older and point toward strategies that might help.
What NAD+ Actually Is
NAD+ stands for nicotinamide adenine dinucleotide, a coenzyme found in every living cell. It exists in two forms: NAD+ (oxidized) and NADH (reduced). These forms work together in what’s called redox reactions, shuttling electrons between molecules to power cellular processes.
Think of NAD+ as a cellular taxi service. It picks up electrons from nutrients you eat (carbohydrates, fats, proteins) and delivers them to your mitochondria, where they’re used to produce ATP, the energy currency your cells run on.
Without NAD+, this entire system breaks down. Your cells can’t convert food into energy efficiently, and critical maintenance functions start to fail.
But NAD+ does more than just facilitate energy production. It also serves as a substrate for enzymes that regulate cellular health, including sirtuins, PARPs (poly ADP-ribose polymerases), and CD38. These enzymes use NAD+ to perform essential tasks like repairing damaged DNA, controlling inflammation, and maintaining the health of your mitochondria.
Why NAD+ Levels Drop With Age
NAD+ levels can decline by as much as 50% between youth and middle age. This isn’t a minor shift. It’s a fundamental change in your cellular environment that affects nearly every system in your body.
Several factors contribute to this decline.
Increased Consumption
As you age, your cells face more stress. DNA damage accumulates from environmental exposures, oxidative stress, and normal metabolic processes. Enzymes like PARPs respond by using NAD+ to repair this damage, but the more damage there is, the more NAD+ gets consumed.
CD38, an enzyme that becomes more active with age, also breaks down NAD+ at an accelerated rate. Studies have shown that CD38 activity increases significantly in older tissues, creating a drain on NAD+ stores that compounds over time.
Reduced Production
Your body makes NAD+ through several pathways, primarily from precursors like nicotinamide, nicotinic acid, and tryptophan. As you age, the efficiency of these pathways decreases. The enzymes responsible for converting precursors into NAD+ become less active, and cellular machinery for synthesis becomes less efficient.
This means your body is both using more NAD+ and making less of it, creating a widening gap that leads to depletion.
Mitochondrial Dysfunction
Mitochondria are the powerhouses of your cells, and they rely heavily on NAD+ to function. As mitochondria age and accumulate damage, they become less efficient at producing energy, which creates a feedback loop. Damaged mitochondria produce more oxidative stress, which causes more DNA damage, which consumes more NAD+, which further impairs mitochondrial function.
This cycle accelerates the decline of NAD+ and contributes to many age-related symptoms like fatigue, reduced stamina, and cognitive decline.
What Happens When NAD+ Levels Drop
The consequences of NAD+ depletion are broad because NAD+ is involved in so many fundamental processes. When levels fall, cells lose their ability to maintain optimal function.
Energy Production Suffers
Lower NAD+ means your mitochondria can’t produce ATP as efficiently. This shows up as physical fatigue, reduced endurance, and a general sense of being run down. Your muscles don’t recover as quickly, and activities that used to feel easy start requiring more effort.
DNA Repair Slows Down
Your DNA is constantly being damaged and repaired. NAD+ dependent enzymes like PARPs are responsible for fixing breaks in DNA strands. When NAD+ is scarce, repair slows down, and damaged DNA accumulates. Over time, this contributes to cellular aging and increases the risk of age-related diseases.
Studies have demonstrated that boosting NAD+ levels in aged mice improved DNA repair capacity and reduced markers of cellular aging, suggesting a direct link between NAD+ availability and genomic stability.
Metabolic Function Declines
NAD+ plays a role in regulating metabolism, including glucose and lipid processing. When levels drop, metabolic flexibility decreases. Your body becomes less efficient at switching between burning carbohydrates and fats for fuel, which can contribute to weight gain, insulin resistance, and metabolic syndrome.
Cognitive Function Deteriorates
The brain is one of the most metabolically active organs in your body, and it’s particularly sensitive to NAD+ depletion. Lower NAD+ is associated with reduced neuronal function, impaired memory, and increased risk of neurodegenerative diseases.
Studies in animal models have shown that restoring NAD+ levels can improve cognitive function, enhance synaptic plasticity, and protect against age-related cognitive decline.
Inflammation Increases
NAD+ helps regulate inflammatory pathways through its role in sirtuin activation. When NAD+ is low, sirtuins become less active, and inflammatory signaling can increase. Chronic low-grade inflammation, often called “inflammaging,” is a hallmark of aging and contributes to many age-related diseases.
Can You Restore NAD+ Levels?
The decline in NAD+ isn’t necessarily irreversible. Several strategies have been studied for their potential to raise NAD+ levels and improve cellular function.
NAD+ Precursors
Supplements like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are NAD+ precursors that your body can convert into NAD+. Research has shown that these compounds can increase NAD+ levels in both animal models and humans, with measurable effects on energy metabolism and cellular health.
However, oral supplementation has limitations. Bioavailability can vary, and high doses may be needed to achieve significant increases in tissue NAD+ levels.
Direct NAD+ Administration
Intravenous NAD+ therapy delivers the molecule directly into your bloodstream, bypassing the need for conversion. This approach provides immediate availability at the cellular level and has been explored for its potential to support energy, cognitive function, and overall wellness.
NAD+ IV therapy is increasingly used in clinical and wellness settings for people dealing with fatigue, cognitive decline, or age-related symptoms, offering a direct method to replenish cellular stores.
Lifestyle Factors
Certain lifestyle interventions can also influence NAD+ levels. Caloric restriction, intermittent fasting, and regular exercise have all been shown to boost NAD+ production or reduce its consumption. These approaches work by activating enzymes involved in NAD+ synthesis and by reducing the cellular stress that depletes NAD+.
The Research Continues
Scientists are still working to fully understand the role of NAD+ in aging and disease. Research has shown that caloric restriction, which is known to extend lifespan in many organisms, works in part by increasing NAD+ levels and activating longevity pathways.
Other studies are investigating whether restoring NAD+ can slow or reverse specific age-related conditions, from metabolic disorders to neurodegenerative diseases. While the field is still evolving, the evidence so far suggests that NAD+ plays a central role in how we age and how well we maintain function over time.
Final Thoughts
NAD+ isn’t a magic bullet, but it’s a critical piece of the aging puzzle. Its decline with age affects energy, repair, metabolism, and resilience at the cellular level. Understanding this connection opens up possibilities for intervention, whether through lifestyle changes, supplementation, or direct replenishment.
As research continues, NAD+ may prove to be one of the most important targets for supporting healthy aging and maintaining quality of life as we get older.
