What Is NAD+ and Why Does It Decline With Age?

NAD+ is one of those molecules you keep hearing about in longevity and “cellular energy” conversations. But what is it really – and why does everyone say it drops as we get older?

This article gives a clear, research-based answer in plain language.

What is NAD+?

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in every cell in your body.

You can think of it as:

  • a key helper for turning food into cellular energy (ATP) in the mitochondria

  • a co-factor for enzymes that repair DNA

  • a signal molecule used by longevity-related proteins like sirtuins and PARPs

Recent reviews in leading medical journals describe NAD+ as a central node that connects many “hallmarks of aging”: mitochondrial dysfunction, DNA damage, impaired stress responses, and chronic inflammation. 

When NAD+ is low, these systems struggle to perform optimally.

What does NAD+ actually do?

The main roles, simplified:

  1. Energy production
    NAD+ shuttles electrons in reactions that generate ATP. Without enough NAD+, your mitochondria can’t produce energy efficiently. PubMed

  2. DNA repair and genome stability
    NAD+ fuels enzymes (like PARPs and sirtuins) that detect and repair DNA damage and help maintain chromosome integrity. PubMed

  3. Cellular stress responses and “longevity pathways”
    Sirtuins, often called “longevity proteins,” depend on NAD+ to regulate metabolism, inflammation, mitochondrial quality control and cellular stress resistance. PubMed

  4. Metabolic and immune regulation
    Changes in NAD+ influence insulin sensitivity, inflammatory signaling and immune cell function – all crucial for healthy aging. Nature

Because NAD+ touches so many systems, even moderate changes in its levels can have broad effects.

Does NAD+ really decline with age?

In short: yes – but it’s tissue-specific and more complex than a simple straight line.

Animal and cell studies

Multiple studies in mice and other models show a clear age-related decrease in NAD+ in tissues such as skeletal muscle, liver, adipose tissue and brain. Restoring NAD+ in these models often improves healthspan and delays features of aging. 

Human data

Human data is newer but growing:

  • Imaging studies of healthy adults using advanced MRI/MRS techniques suggest whole-brain NAD+ levels fall by roughly 10–25% from young adulthood to older age. 

  • Clinical and ex vivo studies indicate that NAD+ can decline with age in some tissues (e.g. skeletal muscle, skin, possibly liver), while remaining more stable in others. 

A 2025 review on NAD+ dynamics in human ageing concluded that age-related NAD+ decline is real but not uniform: it depends on the tissue, individual health status and environmental factors. 

There is still debate – one 2021 review even asked whether “age-dependent NAD+ decline” is a universal truth or context-dependent phenomenon – but the consensus is moving toward: In many people and tissues, NAD+ availability tends to fall with age and chronic disease.

Why does NAD+ decline as we age?

Current evidence points to several overlapping mechanisms:

  1. Increased NAD+ consumption

    • DNA damage accumulates with age → PARP enzymes use more NAD+ for repair.

    • Chronic low-grade inflammation activates CD38 and other NAD-consuming enzymes on immune cells.
      Result: more NAD+ is burned just to keep up with stress. 

  2. Reduced NAD+ production / recycling

    • The salvage pathway (recycling vitamin B3 forms back to NAD+) becomes less efficient in some tissues.

    • Changes in key enzymes (like NAMPT) and nutrient availability can impair this recycling.

    • Metabolic and lifestyle stressors

    • Overnutrition, inactivity, obesity and metabolic disease increase oxidative stress and inflammation, which further drive NAD+ consumption and impair synthesis. 

  3. Disease-specific factors

    • Neurodegeneration, cardiovascular disease, fatty liver and kidney disease have all been associated with disturbed NAD+ metabolism in human and animal studies. 

In other words, aging + modern lifestyle = higher NAD+ demand and lower NAD+ supply in many tissues.

Why does this matter for longevity?

Because NAD+ is involved in:

  • mitochondrial energy

  • DNA repair

  • inflammation control

  • cell survival and stress resilience

most experts now see NAD+ homeostasis as one of the key biological levers in aging. 

So the most evidence-based message today is:

Keeping NAD+ pathways healthy – through lifestyle and targeted supplementation under professional guidance – is a promising way to support cellular resilience and healthy aging, but not yet a guaranteed “anti-aging cure.”

References:

  • Chini CCS, et al. NAD metabolism: role in senescence regulation and aging. Aging Cell. 2024. PubMed+2Wiley Online Library+2

  • Lautrup S, et al. Roles of NAD+ in Health and Aging. Cold Spring Harb Perspect Med. 2024;14(1):a041193. perspectivesinmedicine.cshlp.org+2PubMed+2

  • McReynolds MR, et al. Age-related NAD+ decline. Mech Ageing Dev. 2020. PMC

  • Yusri K, et al. The role of NAD+ metabolism and its modulation in aging and chronic disease. Nat Rev Bioeng. 2025. Nature

  • Iqbal T, et al. The therapeutic perspective of NAD+ precursors in age-related diseases. Biochim Biophys Acta Gen Subj. 2024. ScienceDirect+1

  • Peluso A, et al. Age-dependent decline of NAD+—universal truth or confounded artifact? Nutrients. 2021. MDPI

  • Khatri S, et al. Clinical evidence for the use of NAD+ precursors to slow aging. GeroMedicine. 2025. sciexplor.com+1

  • Dean G. Whole-Brain NAD+ Levels Decline with Age, New Study Shows. NAD.com News, 2024. NAD.com+1