NAD+ Explained: What It Does and Why It Declines With Age

Disclaimer: This article is for educational purposes only and does not provide medical advice. It is not intended to diagnose, treat or prevent disease. Always consult a qualified professional before making health or supplement decisions.

If you’ve spent any time in longevity circles, you’ve probably heard about NAD+. It’s often described as an “anti-ageing molecule” — which is both partly true and partly oversimplified.

NAD+ (nicotinamide adenine dinucleotide) is involved in nearly every aspect of cellular energy production, repair signalling and metabolic adaptation. Without enough NAD+, cells struggle to generate energy efficiently, repair damage, and respond to stress.

Unfortunately, NAD+ levels gradually decline with age — contributing to fatigue, reduced resilience and slower recovery.

This guide explains what NAD+ actually does, why it falls over time, and how lifestyle supports healthy NAD+ levels without hype.

1) The simple explanation

Think of NAD+ as a cellular battery charger and signal messenger combined.

It helps:

• convert food into usable energy
• power mitochondrial function
• activate repair enzymes
• regulate metabolic adaptation

When NAD+ levels are high, cells respond well to stress and recovery. When NAD+ levels fall, energy production and repair capacity gradually weaken.

2) What NAD+ actually does in the body

NAD+ is a coenzyme present in every living cell. It cycles between two forms (NAD+ and NADH) to transfer electrons during metabolic reactions.

In simple terms, NAD+ allows cells to extract energy from carbohydrates, fats and proteins.

Beyond energy production, NAD+ also activates signalling proteins such as:

• Sirtuins (cellular stress resistance and repair)
• PARPs (DNA repair enzymes)
• AMPK (energy sensing pathways)

These pathways regulate longevity-related processes across tissues.

Related: mTOR & AMPK Explained.

3) NAD+ and cellular energy production

NAD+ is essential for mitochondrial energy generation. It carries electrons into the electron transport chain where ATP is produced.

When NAD+ availability drops:

• mitochondrial output declines
• fatigue increases
• exercise tolerance falls
• metabolic flexibility weakens

This links directly to: Mitochondria & Ageing and Mitochondrial Biogenesis.

4) NAD+ and cellular repair systems

NAD+ activates enzymes responsible for:

• DNA repair
• protein quality control
• stress resistance signalling
• mitochondrial maintenance

As NAD+ declines, repair efficiency gradually falls.

See: DNA Damage & Repair and Proteostasis Explained.

5) Why NAD+ declines with age

Increased DNA repair demand

DNA damage increases with age, consuming more NAD+ through repair enzymes.

Chronic inflammation

Immune activation accelerates NAD+ depletion.

Related: Stress and Inflammation.

Reduced precursor availability

Dietary and metabolic production pathways become less efficient.

Mitochondrial dysfunction

Impaired energy metabolism disrupts NAD+ recycling.

See: Oxidative Stress Explained.

6) How NAD+ connects to other ageing pathways

• Mitochondria: energy production capacity
• DNA repair: genomic stability
• Proteostasis: protein maintenance
• Inflammation: immune regulation
• Metabolic signalling: insulin sensitivity

Explore: Glycation & AGEs, Cellular Senescence and Insulin Resistance.

7) How to support NAD+ naturally

Regular physical activity

Exercise stimulates NAD+ recycling and mitochondrial adaptation.

Protect sleep and circadian rhythm

Repair signalling depends on stable sleep timing.

See: Sleep for Longevity.

Maintain metabolic stability

Stable blood sugar preserves NAD+ balance.

Moderate caloric excess

Chronic overfeeding accelerates NAD+ depletion.

Manage chronic stress

Stress signalling increases repair demand and NAD+ consumption.

Related: Stress and Longevity.

8) A note on NAD+ supplements

NAD+ precursors such as NR and NMN can increase blood NAD+ levels. However, long-term outcome data remains limited.

Supplements should be viewed as experimental and secondary to lifestyle foundations.

FAQ

Does NAD+ supplementation slow ageing?

Human evidence remains limited. Benefits appear context-dependent.

Can NAD+ levels be measured?

Blood testing exists but does not reflect tissue levels reliably.

Does fasting increase NAD+?

Fasting may transiently increase NAD+ signalling pathways.

Is more NAD+ always better?

Balance matters. Excess stimulation may have unintended effects.

Final takeaway

NAD+ supports energy production, repair and metabolic flexibility.

Protecting sleep, movement, metabolic health and stress regulation preserves NAD+ far more reliably than chasing supplements.

— Simon

References

• Verdin E. (2015). NAD+ in aging, metabolism, and neurodegeneration. Science.
• Rajman L et al. (2018). Therapeutic potential of NAD+ boosting molecules. Cell Metabolism.