Why do NAD⁺ levels naturally decline with age?

If you’re someone who takes your health seriously, you may have come across the term NAD⁺. Short for nicotinamide adenine dinucleotide, this essential molecule is involved in nearly every biological process that keeps us alive and well, from generating energy to repairing DNA. 

However, what many people don’t know is that our levels of NAD⁺ decline significantly as we age, and this quiet decline may be at the heart of many age-related issues, both physical and cognitive.

In this article, we’ll explore why NAD⁺ levels fall with age, what it means for your health, and what science says we can do to maintain and restore it naturally, and through targeted supplementation.

What Is NAD⁺ and why is it important?

NAD⁺ is a coenzyme found in every living cell. It plays a central role in converting the food we eat into usable energy by facilitating mitochondrial function. But its role doesn’t stop there. NAD⁺ is also vital in regulating cellular stress responses, repairing damaged DNA, supporting circadian rhythm, and activating longevity-associated enzymes called sirtuins. In other words, NAD⁺ helps keep your cells functioning optimally, and your body resilient.

What causes NAD⁺ levels to drop with age?

Research shows that NAD⁺ levels begin to decline noticeably from around age 30 and continue dropping throughout life. By the time we reach our 60s, NAD⁺ levels may be less than half of what they were in our youth1. So, what causes this decline? There are several interrelated factors:

1. Increased NAD⁺ consumption: As we age, our bodies experience more oxidative stress, DNA damage, and inflammation. These stressors trigger enzymes like PARPs and CD38, which consume NAD⁺ as they work to repair damage or regulate immune responses.

2. Reduced NAD⁺ biosynthesis: Our ability to create NAD⁺ from precursor molecules – such as tryptophan, niacin (vitamin B3), or nicotinamide mononucleotide (NMN) – diminishes with age, due to lower activity in key enzymes along the NAD⁺ biosynthetic pathways.

3. Mitochondrial decline: Aging also impairs mitochondrial function. Since mitochondria are both a major consumer and regulator of NAD⁺, this leads to a feedback loop of declining cellular energy and reduced NAD⁺ availability.

When does the decline start?

NAD⁺ decline begins gradually in the early 30s, accelerating into the 40s and beyond. However, the rate of decline varies by individual and can be influenced by genetics, lifestyle, exposure to environmental toxins, and stress. For instance, a study published in Cell Metabolism found that levels of NAD⁺ in tissues like skin, blood, and muscle decrease by 50% or more between youth and late middle age.

How does NAD⁺ decline affect the body and mind?

Low NAD⁺ levels don’t just mean less energy. The impacts are broad and significant, affecting almost every system in the body:

• Energy & Metabolism: As NAD⁺ levels fall, mitochondrial efficiency drops, leading to fatigue, weight gain, and metabolic slow downs.

• Cognitive Function: NAD⁺ is crucial for brain health. Lower levels are associated with cognitive decline, memory issues, and reduced neuroplasticity.

• Muscle Health: Decreased NAD⁺ contributes to muscle weakness and reduced exercise capacity. One study showed that restoring NAD⁺ levels in older animals improved muscle function and endurance.

• Inflammation & Immunity: Chronic low-grade inflammation (inflammaging) is a hallmark of aging, and it’s partly driven by NAD⁺ depletion and over-activation of immune-regulating enzymes.

• DNA Repair & Longevity: With lower NAD⁺, DNA damage accumulates more rapidly. The sirtuin family of proteins – often called “longevity enzymes” – rely on NAD⁺ to function. Without it, their protective role diminishes.
  

Slowing the decline of NAD+ naturally

While the decline in NAD⁺ with age is natural, there are ways to preserve and even boost your NAD⁺ levels:

1. Exercise regularly. Aerobic exercise is one of the most well-researched ways to increase NAD⁺ naturally. It enhances mitochondrial function and stimulates production of NAD⁺ biosynthesis enzymes.
2. Practice intermittent fasting or caloric restriction. Studies have shown that intermittent fasting increases NAD⁺ levels and activates sirtuins, mimicking the effects of higher NAD⁺ availability.
3. Avoid excessive alcohol and sugar. These dietary choices can increase oxidative stress and inflammation, depleting NAD⁺. A diet rich in colourful vegetables, healthy fats, and lean protein supports better NAD⁺ homeostasis.
4. Prioritise sleep and circadian rhythm. NAD⁺ levels follow a circadian rhythm, and poor sleep can disrupt this balance. Keeping consistent sleep and wake times helps maintain NAD⁺ and sirtuin activity.

Supplementation: a targeted way to rebuild NAD⁺

In addition to lifestyle changes, targeted supplementation offers a promising path to restoring NAD⁺ levels, especially in those over 30.

The Most Promising NAD⁺ Precursors:

• NMN (Nicotinamide Mononucleotide): NMN is a direct precursor to NAD⁺ and has been shown in animal and early human studies to increase NAD⁺ levels, improve insulin sensitivity, support mitochondrial health, and boost endurance.

• NR (Nicotinamide Riboside): Another NAD⁺ precursor, NR has also shown effectiveness in elevating NAD⁺ and supporting metabolic and cognitive function.

• Supporting nutrients: Nutrients like vitamin B3 (niacinamide), magnesium, and resveratrol can support NAD⁺ pathways and work synergistically with NMN or NR.

At Uthful, our formulation is built on these emerging insights, blending clinically studied NAD⁺ precursors like NMN with natural co-factors and adaptogens to support healthy energy, cognition, and resilience from the inside out.

The bottom line

The decline in NAD⁺ with age is both measurable and meaningful. It underlies many of the changes we associate with aging: slower metabolism, lower energy, increased inflammation, and cognitive decline. But we are not powerless. With consistent lifestyle practices and targeted supplementation, it’s possible to restore NAD⁺ levels and support cellular health well into midlife and beyond. And here at Uthful, we’re committed to bringing clarity, science, and efficacy to the world of longevity. 

Footnotes

1. Massudi, H. et al. (2012). Age-Associated Changes In Oxidative Stress and NAD⁺ Metabolism in Human Tissue. PLOS ONE, 7(7): e42357. 

2. Bai, P. et al. (2011). PARP-1 Inhibition Increases Mitochondrial Metabolism Through SIRT1 Activation. Cell Metabolism, 13(4), 461–468. 

3. Camacho-Pereira, J. et al. (2016). CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction. Cell Metabolism, 23(6), 1127–1139. 

4. Yoshino, J. et al. (2018). NAD⁺ Intermediates: The Biology and Therapeutic Potential of NMN and NR. Cell Metabolism, 27(3), 513–528.

5. Gomes, A.P. et al. (2013). Declining NAD⁺ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication During Aging. Cell, 155(7), 1624–1638. 

6. Hou, Y. et al. (2018). NAD⁺ Supplementation Normalizes Key Alzheimer’s Features and DNA Damage Responses in a New AD Mouse Model. npj Aging and Mechanisms of Disease, 4(1), 1–10. 

7. Zhang, H. et al. (2016). NAD⁺ Repletion Improves Mitochondrial and Stem Cell Function and Enhances Life Span in Mice. Science, 352(6292), 1436–1443. 

8. Covarrubias, A.J. et al. (2021). NAD⁺ Metabolism and Immunometabolism: A Golden Age for NAD⁺. Journal of Biological Chemistry, 296, 100416. 

9. Imai, S. & Guarente, L. (2014). NAD⁺ and Sirtuins in Aging and Disease. Trends in Cell Biology, 24(8), 464–471. 

10. Costford, S.R. et al. (2010). Skeletal Muscle NAMPT is Induced by Exercise in Humans. American Journal of Physiology-Endocrinology and Metabolism, 298(1), E117–E126. 

11. Canto, C. & Auwerx, J. (2009). Calorie Restriction: Is SIRT1 a Mediator? Trends in Endocrinology & Metabolism, 20(7), 325–331. 

12. Peek, C.B. et al. (2013). Circadian Clock NAD⁺ Cycle Drives Mitochondrial Metabolism. Nature, 495(7441), 351–355. 

13. Imai, S. et al. (2016). The NAD World: A New Systemic Regulatory Network for Metabolism and Aging—Sirtuins and a Novel Mediator NMN. Cell Research, 26(1), 1–14. 

14. Trammell, S.A.J. et al. (2016). Nicotinamide Riboside Opposes Type 2 Diabetes and Neuropathy in Mice. Scientific Reports, 6, 26933.