What is NAD+?
NAD+ (Nicotinamide Adenine Dinucleotide) is a coenzyme present in every living cell, functioning as an essential electron carrier in cellular metabolism and a substrate for a class of enzymes with broad regulatory functions. Its levels decline significantly with age — a fact that has made it one of the most studied molecules in longevity and aging biology research over the past decade.
What NAD+ Is and Does
NAD+ is a dinucleotide — a molecule composed of two nucleotides joined by phosphate groups — found in all living cells. It exists in two interconvertible forms: NAD+ (oxidized) and NADH (reduced). The cell cycles between these two forms during metabolic reactions, with NAD+ accepting electrons (becoming NADH) and NADH donating them back (regenerating NAD+).
This redox cycling makes NAD+/NADH central to virtually all cellular energy metabolism. In the electron transport chain, NADH donates electrons that drive the production of ATP — the cell's energy currency. Without adequate NAD+, the electron transport chain cannot function efficiently, and cellular energy production declines.
Why NAD+ Declines With Age
NAD+ levels in human tissue decline substantially with age. Research estimates suggest levels at age 60 may be roughly half those at age 20, with the decline beginning in early adulthood and accelerating in middle age. Several mechanisms contribute to this decline:
Increased PARP consumption: PARP enzymes (poly ADP-ribose polymerases) consume NAD+ as a substrate during DNA damage repair. As DNA damage accumulates with age, PARP activity increases, consuming more NAD+ than biosynthesis can replenish.
Reduced biosynthesis: The enzymes responsible for NAD+ synthesis decline in activity with age, reducing the rate at which NAD+ can be replenished from precursors.
Increased CD38 activity: CD38, an enzyme that consumes NAD+, increases in expression with age and in states of chronic inflammation, further depleting cellular NAD+ pools.
NAD+ and Sirtuins
One of the most significant research connections involving NAD+ is its relationship with sirtuins — a family of seven proteins (SIRT1-7) that require NAD+ as a substrate to function. Unlike most enzymes that merely need a cofactor present, sirtuins actually consume NAD+ during their catalytic cycle.
Sirtuins regulate a broad range of biological processes: SIRT1 and SIRT6 are involved in DNA repair coordination and gene expression regulation. SIRT3, SIRT4, and SIRT5 are located in mitochondria and regulate mitochondrial metabolism. SIRT2 regulates cell cycle progression. SIRT7 is involved in ribosome biogenesis and stress response.
The dependence of sirtuins on NAD+ means that declining NAD+ levels with age may directly limit sirtuin activity — creating a feedback loop where reduced sirtuin function further impairs the cellular maintenance processes sirtuins regulate. This NAD+-sirtuin connection is a central area of aging biology research.
Research Applications
NAD+ is used in research across several domains:
Aging biology: Studies examining whether NAD+ restoration to younger levels can reverse age-associated cellular dysfunction. Research in animal models has demonstrated improved mitochondrial function, DNA repair capacity, and metabolic parameters with NAD+ supplementation.
Mitochondrial research: NAD+ is central to mitochondrial electron transport function. Research investigates how NAD+ availability affects mitochondrial biogenesis, respiration efficiency, and reactive oxygen species production.
DNA repair: PARP-mediated DNA repair is NAD+-dependent. Research examines how NAD+ availability affects DNA repair capacity under conditions of oxidative stress and genotoxic damage.
Metabolic research: NAD+ influences insulin sensitivity, glucose metabolism, and fatty acid oxidation through sirtuin and AMPK pathway interactions.
Reconstitution and Storage
NAD+ requires more careful handling than most research peptides due to its sensitivity to both light and heat.
Reconstitution: For 500mg: add 5mL BAC Water (100mg/mL). For 1000mg: add 10mL BAC Water (100mg/mL) — a 30mL sterile transfer vial is recommended. NAD+ may require several minutes of gentle swirling to fully dissolve. Do not shake.
Light sensitivity: Wrap the vial in aluminum foil immediately after reconstitution. Light degrades NAD+ at a measurable rate. Keep wrapped during storage and minimize exposure during draws.
Stability: Reconstituted NAD+ is stable 14-21 days refrigerated at 2-8°C — shorter than most peptides. Use promptly after reconstitution. Do not freeze.