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NAD+

LongevityCoenzyme (dinucleotide)
·663 Da·C₂₁H₂₇N₇O₁₄P₂
Peptide Database
4Mechanisms
5Benefits
20Studies

Nicotinamide adenine dinucleotide (NAD+) is not a peptide but a coenzyme found in all living cells. It is a dinucleotide consisting of two nucleotides (one with adenine, one with nicotinamide) joined through their phosphate groups. NAD+ is essential for cellular energy metabolism and is synthesized endogenously from precursors including tryptophan, niacin, nicotinamide riboside, and NMN.

Research Dosage Notes

IV NAD+ infusions at longevity clinics typically use 250-500 mg per session over 2-4 hours, with loading protocols of 4-10 sessions over 10-14 days followed by monthly maintenance at 500-1000 mg. Oral supplementation is poorly bioavailable, which is why precursors (NMN, NR) are often preferred for oral use. Subcutaneous injections of 50-100 mg are also used in some clinical settings. Not FDA-approved as a therapeutic.

Mechanisms of Action

4

Redox coenzyme in energy metabolism

Strong

Serves as the primary electron carrier in cellular respiration, shuttling electrons in glycolysis, the citric acid cycle, and oxidative phosphorylation to drive ATP production.

Glycolysis/TCA cycle/electron transport chain

Sirtuin activation (SIRT1-7)

Strong

Acts as an obligate co-substrate for sirtuins, NAD-dependent deacetylases that regulate DNA repair, gene expression, metabolism, and aging. Declining NAD+ levels with age reduce sirtuin activity.

Sirtuin/NAD+ signaling

PARP-mediated DNA repair

Strong

Required substrate for poly(ADP-ribose) polymerases (PARPs), which detect and repair DNA damage. NAD+ depletion impairs DNA repair capacity.

PARP/DNA damage response

CD38/NADase regulation

Moderate

NAD+ is consumed by CD38 (a NADase enzyme that increases with aging), contributing to age-related NAD+ decline. Modulating this axis is a target for longevity interventions.

CD38/NAD+ consumption

Benefits

5
90

Cellular energy production

Metabolic

Fundamental to mitochondrial ATP production. Restoring NAD+ levels may improve cellular energy output and reduce fatigue associated with aging.

Strong
70

Anti-aging and longevity

Longevity

NAD+ repletion extends lifespan in yeast, worms, and mice. Activates sirtuins involved in longevity pathways and improves age-related functional decline in animal models.

Moderate
70

DNA repair enhancement

Longevity

Supports PARP-mediated DNA repair, potentially reducing accumulation of DNA damage associated with aging and cancer risk.

Moderate
60

Neuroprotection

Cognitive

NAD+ supplementation ameliorates age-associated neurodegenerative conditions in animal models, potentially through improved mitochondrial function and reduced oxidative stress.

Moderate
60

Cardiovascular protection

Metabolic

NAD+ repletion improves endothelial dysfunction and protects against experimental heart failure in animal models.

Moderate

Research Studies

20
2025

Teduglutide is a glucagon-like peptide-2 analogue used to promote intestinal rehabilitation and decr...

Clinical nutrition (Edinburgh, Scotland) · Francisca Joly, Denise Jezerski, Ulrich-Frank Pape, Adriana ...

2023

Interactions between Intestinal Homeostasis and NAD

Nutrients · Taichi Nagahisa, Shotaro Kosugi, Shintaro Yamaguchi

2023

Human sirtuins play important roles in various cellular events including DNA repair, gene silencing,...

The FEBS journal · Alyson M Curry, Stacia Rymarchyk, Noah B Herrington, Dickson...

2023

Extended Biocatalytic Halogenation Cascades Involving a Single-Polypeptide Regeneration System for Diffusible FADH

Chembiochem : a European journal of chemical biology · Nicolai Montua, Norbert Sewald

2023

Coacervate droplets are promising protocell models because they sequester a wide range of guest mole...

Nature communications · Jiahua Wang, Manzar Abbas, Junyou Wang, Evan Spruijt

This database is for educational and research purposes only. It is not medical advice. Consult a healthcare professional before using any peptide or supplement.

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