What Is NAD+?

NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme found in every living cell. It exists in two forms: NAD+ (oxidized) and NADH (reduced). This molecule is absolutely essential for life โ€” without it, cellular energy production would cease.

Molecular Formula: C21H27N7O14P2 Molecular Weight: 663.43 g/mol Discovery: 1906 by Arthur Harden and William John Young Nobel Connection: Multiple Nobel Prizes linked to NAD+ research

While not a peptide, NAD+ is frequently discussed alongside peptide research due to its central role in cellular health and its inclusion in many longevity research protocols.

Key Characteristics

  • Essential: Required for over 500 enzymatic reactions
  • Universal: Present in all living organisms
  • Age-Related Decline: Levels decrease significantly with age
  • Energy Currency: Central to ATP production

Biological Functions

Energy Metabolism

NAD+ is central to cellular energy production:

  • Glycolysis: NAD+ accepts electrons during glucose breakdown
  • Krebs Cycle: Multiple NAD+-dependent steps
  • Electron Transport Chain: NADH delivers electrons for ATP synthesis
  • ATP Production: Each NADH can generate ~2.5 ATP molecules

Sirtuin Activation

NAD+ is the essential substrate for sirtuins (SIRT1-7):

  • SIRT1: Regulates metabolism, stress response, longevity pathways
  • SIRT3: Mitochondrial function and antioxidant defense
  • SIRT6: DNA repair and genomic stability
  • Without NAD+, sirtuins cannot function

DNA Repair

NAD+ supports DNA maintenance:

  • Substrate for PARP enzymes (poly ADP-ribose polymerases)
  • PARPs consume NAD+ during DNA damage repair
  • Excessive DNA damage can deplete NAD+ pools
  • Adequate NAD+ supports genomic integrity

Cellular Signaling

Beyond metabolism, NAD+ participates in signaling:

  • CD38 enzyme activity regulation
  • Calcium signaling pathways
  • Circadian rhythm maintenance
  • Immune cell function

NAD+ and Aging

A central theme in longevity research is the decline of NAD+ with age:

Age-Related NAD+ Decline

  • NAD+ levels can drop by 50% between ages 40-60
  • CD38 expression increases with age, consuming more NAD+
  • Chronic inflammation elevates NAD+ consumption
  • DNA damage accumulation depletes NAD+ pools

This decline correlates with many hallmarks of aging, including mitochondrial dysfunction, increased inflammation, and reduced cellular repair capacity.

Research Areas

Longevity and Healthspan

  • NAD+ supplementation (via precursors) extends lifespan in animal models
  • Improved metabolic function in aged animals
  • Enhanced physical performance and endurance
  • Maintained cognitive function in aging studies

Metabolic Health

  • Insulin sensitivity improvements in animal studies
  • Obesity and metabolic syndrome research
  • Fatty liver disease models
  • Diabetes research

Neurological Research

  • Alzheimer's disease models
  • Parkinson's disease research
  • Traumatic brain injury recovery
  • Cognitive decline prevention

Cardiovascular Research

  • Heart failure models
  • Vascular aging
  • Blood pressure regulation
  • Cardiac protection studies

NAD+ Precursors

Because NAD+ itself has poor bioavailability, research focuses on precursor compounds:

Precursor Full Name Pathway Notes
NMN Nicotinamide Mononucleotide Salvage Direct NAD+ precursor
NR Nicotinamide Riboside Salvage Converts to NMN then NAD+
NA Nicotinic Acid (Niacin) Preiss-Handler Classic B3 vitamin; causes flushing
NAM Nicotinamide Salvage May inhibit sirtuins at high doses
Trp Tryptophan De novo Amino acid; inefficient pathway

Key Published Research

Year Focus Key Finding Reference
2013 Aging NAD+ decline linked to aging Gomes et al., Cell
2016 NMN efficacy NMN improved metabolism in mice Mills et al., Cell Metabolism
2018 Vascular aging NAD+ restored vascular function Das et al., Cell
2020 Human trial NMN raised NAD+ in humans safely Yoshino et al.
2021 Exercise NMN enhanced exercise capacity Liao et al.

Human Clinical Trials

NAD+ precursors (particularly NMN and NR) are among the few longevity compounds with human clinical data:

  • Multiple trials confirm safety of NMN and NR supplementation
  • Demonstrated ability to raise blood NAD+ levels in humans
  • Some studies show improved insulin sensitivity
  • Exercise performance benefits in some populations
  • Long-term efficacy studies still ongoing

Current Status

NAD+ precursors like NMN and NR are available as supplements in many countries. While generally considered safe based on current research, they are not FDA-approved drugs. Long-term effects and optimal dosing protocols in humans are still being established through ongoing research.

Summary

NAD+ represents one of the most fundamental molecules in biology and has emerged as a central target in longevity research. The age-related decline in NAD+ levels and its correction through precursor supplementation offers a promising avenue for supporting healthspan. With human clinical trials already demonstrating safety and bioavailability, NAD+ research continues to be one of the most active areas in the longevity field.

โ† LL-37 Research Next: NMN Research โ†’