NAD+ is consumed by SIRT1β7 (class III HDACs) β histone deacetylation, gene silencing, mitochondrial biogenesis (PGC-1Ξ±). Falls with age β sirtuin hypoactivity
PARP SUBSTRATE
NAD+ fuels PARP-1/2 for DNA repair (ADP-ribosylation). DNA damage consumes NAD+ β catastrophic depletion in aged tissues reduces repair capacity
CD38 / MITOCHONDRIA
CD38 consumes >95% of cellular NAD+. CD38 rises with age β NAD+ depletion loop. NAD+ supplementation β complex I function β, mitochondrial biogenesis via PGC-1Ξ± β
Research Questions Answered
What is NAD+?
NAD+ (Nicotinamide Adenine Dinucleotide) is a universal metabolic coenzyme present in all living cells, functioning in two capacities: as an electron carrier in redox reactions (NAD+/NADH) and as a substrate for enzymes consuming it catalytically β sirtuins (SIRT1β7), PARPs (DNA repair), and CD38/SARM1 (NAD glycohydrolases). NAD+ declines 40β60% from young to old age in most tissues β this decline is mechanistically linked to aging via reduced sirtuin activity, impaired DNA repair, and mitochondrial dysfunction.
How does NAD+ work in longevity research?
NAD+ fuels sirtuins (SIRT1β7, class III HDACs): SIRT1 deacetylates PGC-1Ξ± β mitochondrial biogenesis β. SIRT3 deacetylates mitochondrial proteins β ETC efficiency β. SIRT6 deacetylates histones β DNA repair β. All require NAD+ as substrate. As NAD+ falls with age, sirtuin activity falls β epigenetic dysregulation, reduced mitochondrial quality, impaired DNA repair. NAD+ precursor supplementation research (NMN, NR) tests whether restoring NAD+ restores sirtuin activity.
What is NMN vs NR vs NAD+?
Three compounds for NAD+ metabolism research: NAD+ (direct β high MW, limited cellular uptake). NR (Nicotinamide Riboside) β NAD+ precursor, better absorbed than NAD+, enters NAD+ biosynthesis via NRK1/2. NMN (Nicotinamide Mononucleotide) β direct NAD+ precursor, may enter cells via Slc12a8 transporter, rapidly converted to NAD+ intracellularly. QSC stocks all three. Most published longevity research uses NMN or NR rather than NAD+ directly.
What are sirtuins?
Sirtuins (SIRT1β7) are NAD+-dependent deacylases and deacetylases β the ‘longevity enzymes’. They regulate: epigenetics (histone modification), mitochondrial function, DNA repair, metabolism, inflammation, and circadian rhythms. All 7 require NAD+ as a substrate consumed in the deacylation reaction. Key targets: SIRT1 (nuclear, PGC-1Ξ±, p53), SIRT3 (mitochondrial, ETC), SIRT6 (telomere/DNA repair).
Where can I buy NAD+ for research?
Research-grade NAD+ is available from QSC (qscpeptide.com) at β₯99% HPLC purity with Janoshik COA. Available in 500mg configurations. US Domestic Warehouse: 2β4 business days. Research use only.
How does NAD+ decline with age?
NAD+ declines ~40β60% from age 20 to 80 in most human tissues. Three mechanisms: (1) Reduced biosynthesis (NAMPT enzyme decline); (2) Increased consumption by CD38 (CD38 rises with age, consumes >95% of cellular NAD+); (3) Increased PARP activation (age-related DNA damage increases PARP demand). The result is NAD+ depletion β sirtuin hypoactivity β epigenetic drift β mitochondrial dysfunction.
What is CD38 and why does it matter for NAD+?
CD38 is an NAD+ glycohydrolase β an enzyme that cleaves NAD+ to produce cyclic ADP-ribose (cADPR). CD38 is the dominant consumer of cellular NAD+ (>95% in some tissues) and rises dramatically with age (senescent cell SASP promotes CD38 expression). CD38 inhibition is an emerging NAD+ restoration research strategy alongside NAD+ precursor supplementation.
What is PARP and its relationship to NAD+?
PARP-1 (Poly-ADP ribose polymerase 1) is a DNA repair enzyme that consumes NAD+ to attach ADP-ribose chains to proteins at DNA damage sites. Excessive DNA damage β PARP hyperactivation β catastrophic NAD+ depletion β necrotic cell death (parthanatos). In aging, the burden of DNA damage increases PARP activity β additional NAD+ consumption on top of the CD38 rise. PARP inhibitors are used in cancer research; NAD+ supplementation may partially offset PARP-driven depletion.
How is NAD+ stored?
NAD+ powder: store at β20Β°C, desiccated. Protect from moisture and light. NAD+ is hygroscopic and photo-labile. Reconstituted solution: use within 24 hours ideally, store at 4Β°C briefly. For long-term stability in research protocols, store as lyophilised powder and prepare fresh solutions.
What is NAD+ molecular weight?
NAD+ (Ξ²-nicotinamide adenine dinucleotide, oxidised form) has a molecular weight of 663.43 Da. CAS: 53-84-9. NADH (reduced form): 665.44 Da. The reduced NADH form is distinguished by addition of 2H (hydride transfer).
Where to Buy Research-Grade NAD+
β₯99% HPLC Β· Janoshik COA Β· US Domestic 2β4 Days Β· Research Use Only
