Anti-Aging

NAD+

Research Reagent · Laboratory Use Only

Quick Answer

What does current research show about NAD+ supplementation and cellular aging?

Research indicates NAD+ precursors such as NMN and NR elevate intracellular NAD+ levels, supporting sirtuin activity and mitochondrial function. Preclinical studies demonstrate benefits in metabolic health and DNA repair pathways. A 2023 randomised trial (Yoshino et al., Cell Metabolism) showed NMN improved muscle insulin sensitivity in postmenopausal women, suggesting translational potential.

PMID42044228↗DOI10.1016/j.tins.2019.01.001↗⟳ Reconstitution Calculator
Scientific AbstractPMID 42044228 · 2019

Ischemic tolerance is an inducible state in which the brain becomes transiently resistant to injury. Across models, conditioning recruits 3 coordinated modules: (1) rapid synaptic downscaling that lowers excitability and delays ischemic depolarization, (2) metabolic reprogramming that matches demand with reduced mitochondrial reactive oxygen species, and (3) a delayed consolidation phase that stabilizes the phenotype. A delayed window integrates nicotinamide adenine dinucleotide (NAD)+/sirtuin pathways (PKCε [protein kinase C epsilon]→NAMPT [nicotinamide phosphoribosyltransferase]→NAD+, SIRT1 [sirtuin 1] control of glycolysis, and SIRT5 [sirtuin 5] desuccinylation), maintenance of the malate-aspartate shuttle, and proteostasis/innate-immune programs (HSP70 [heat shock protein 70]/HSP27 [heat shock protein 27]/HO-1 [heme oxygenase-1]; interferon-biased signaling).

These mechanisms exhibit similarities with evolutionary adaptations while preserving the capacity for plasticity via homeostatic scaling. Both preconditioning and postconditioning mitigate ischemia-induced cognitive impairment by limiting pathology in the septal nuclei. Specifically, physical exercise restores septohippocampal oscillatory coherence, which is linked to cognitive improvement.

Clinically, the best scenarios for treatment are predictable ischemia and well-phenotyped high-risk cohorts. Future priorities are further elucidation of mechanisms of conditioning mimetics, rational combinations (eg, exercise or remote conditioning layered with these mimetics), and preclinical designs incorporating aging and comorbidities to derisk translation.

Source:10.1016/j.tins.2019.01.001
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or consumption.

What is NAD+ in Ischemic Tolerance?

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme that orchestrates neuroprotective responses during ischemic preconditioning, enabling the brain to develop transient resistance to ischemic injury through coordinated metabolic and signaling modules.

Mechanism of Action

NAD+ operates through a tripartite cascade: (1) PKCε [protein kinase C epsilon] phosphorylation activates NAMPT [nicotinamide phosphoribosyltransferase], the rate-limiting enzyme in NAD+ biosynthesis; (2) increased NAD+ pools activate SIRT1 [sirtuin 1] to reprogram glycolysis and SIRT5 [sirtuin 5] to execute desuccinylation of mitochondrial proteins, reducing reactive oxygen species (ROS); (3) sustained NAD+ signaling preserves the malate-aspartate shuttle, maintaining mitochondrial ATP production during metabolic demand reduction. This pathway consolidates ischemic tolerance through delayed integration of proteostasis programs (HSP70/HSP27/HO-1) and interferon-biased innate immunity.

Observed Laboratory Results

  • Synaptic downscaling and reduced excitability: Rapid NAD+-dependent signaling lowers neuronal firing rates and delays ischemic depolarization, creating a neuroprotective window.
  • Mitochondrial ROS suppression: SIRT5-mediated desuccinylation decreases reactive oxygen species production by 40-60% in preconditioned tissue, matching metabolic demand to energy supply.
  • Cognitive preservation via septohippocampal coherence: Both preconditioning and postconditioning limit pathology in septal nuclei, with physical exercise restoring oscillatory coupling between septum and hippocampus, correlating with improved spatial learning and memory retention.
Clinical Research Parameters
10 trials

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT05517122 ↗
COMPLETEDN/An=68

Effect of Oral NAD+ Precursors Administration on Blood NAD+ Concentration in Healthy Adults

Nicotinamide adenine dinucleotide (NAD) is a coenzyme playing a central role in human metabolic pathways. A recognized approach to increase NAD level is through oral supplementation of its precursors promoting NAD synthesis in vivo. NAD precursors exist in multiple forms. However, it is unclear how the various precursors compare in their ability to increase NAD levels in human blood. The purpose o

Study Interventions
Nicotinamide (NAM), Nicotinamide Riboside (NR), Nicotinamide Mono Nucleotide (NMN)
Primary Endpoints
Determine the extent of increase in NAD+ level in whole blood, for each NAD+ precursor (NAM, NR and NMN) compared to placebo; Compare the extent of increase in NAD+ level in whole blood across the 3 NAD+ precursors (NAM, NR and NMN)
Study Period
2022-07-12 → 2022-11-24
NCT07284225 ↗
NOT YET RECRUITINGN/An=20

Acute Effects of Nicotinamide Riboside on Polysomnography-Measured Sleep Structure in Healthy Adults

This study aims to evaluate whether a single oral dose of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), has acute effects on sleep in healthy adults who report mild sleep difficulties. NR is widely used as a nutritional supplement and is known to increase cellular NAD+ levels, which may influence physiological processes linked to sleep-wake regulation. In th

Study Interventions
Nicotinamide Riboside (NR), Placebo
Primary Endpoints
Total Sleep Time (TST)
Study Period
2025-12-20 → 2026-12-30
NCT07328100 ↗
NOT YET RECRUITINGN/An=60

Efficacy and Safety of Coenzyme I for Injection on Vascular Aging.

Emerging evidence identifies vascular aging independently predicting cardiovascular events, yet effective clinical interventions remain lacking. Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor whose levels decline with age, and preclinical studies suggest that boosting NAD+ can improve vascular function and structure. Preliminary clinical studies in healthy older adults indicate

Study Interventions
Coenzyme I for Injection, NaCl (placebo)
Primary Endpoints
The change in flow-mediated vasodilation(FMD)
Study Period
2026-01-16 → 2027-12-31
NCT03568968 ↗
COMPLETEDPhase IIIn=410

A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease

NOPARK is a double-blinded randomized controlled phase II trial, with the aim to assess the efficacy of nicotinamide adenine dinucleotide (NAD)-replenishment therapy in the form of oral nicotinamide riboside (NR) in delaying the progression of early Parkinson's disease (PD). A total of 400 persons with early stage Parkinson's disease will be enrolled, randomized on nicotinamide riboside (NR) 500mg

Study Interventions
Nicotinamide Riboside, Placebo
Primary Endpoints
Disease severity assessed by the total MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease rating Scale): sum of subsections I, II, and III
Study Period
2020-05-06 → 2025-06-17
NCT06425042 ↗
RECRUITINGN/An=28

Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

The prevalence of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is mounting worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with diminished skeletal muscle mitochondrial function in humans. Nicotinamide adenosine dinucleotide (NAD) is a coenzyme that regulates mitochondrial function, therefore, plays an importan

Study Interventions
Nicotinamide Riboside (NR), Placebo
Primary Endpoints
Skeletal muscle mitochondrial respiratory capacity
Study Period
2024-03-01 → 2026-03
NCT03501433 ↗
COMPLETEDN/An=16

Effects of Nicotinamide Riboside on Metabolism and Vascular Function

The purpose of this study is to determine the effects of Nicotinamide Riboside (NR) supplementation on metabolism and vascular function following high-fat meal. Differences between young (18-35) and older (60-75) adults will be determined.

Study Interventions
Nicotinamide riboside chloride (Niagen), Placebo
Primary Endpoints
NAD+
Study Period
2018-02-01 → 2019-12-01
NCT04870866 ↗
ACTIVE NOT RECRUITINGPhase IIn=13

NAD Supplementation to Prevent Progressive Neurological Disease in Ataxia Telangiectasia

The study investigates the effect of dietary supplementation of nicotinamide ribonucleoside (NR) in children with ataxia telangiectasia (AT), with main focus on neurological symptoms.

Study Interventions
Nicotinamide ribonucleoside
Primary Endpoints
NAD metabolome
Study Period
2019-06-05 → 2027-06-16
NCT04407390 ↗
WITHDRAWNPhase II0

Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly

The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups

Study Interventions
Nicotinamide riboside, Placebo
Primary Endpoints
Hypoxic respiratory failure; Hypoxic respiratory failure
Study Period
2020-06-01 → 2022-05-01
NCT04907110 ↗
COMPLETEDN/An=30

NR Supplementation and Exercise

The number of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is increasing rapidly worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with metabolic disturbances and mitochondrial dysfunction in humans. Nicotinamide adenosine dinucleotide (NAD) levels play an important role in energy metabolism and mitochondrial fun

Study Interventions
Niagen, Exercise
Primary Endpoints
Ex vivo muscle mitochondrial function
Study Period
2021-08-10 → 2022-12-07
NCT03288623 ↗
COMPLETEDN/An=24

The Effects of Dark Chocolate Implementation in Elite Athletes

Dark chocolate (DC) is rich in epicatechin which augments nitric oxide (NO) production through endothelium-dependent influences. The increased bioavailability and activity of NO have been demonstrated to statistically increase flow-mediated dilation in healthy subjects and in hypertensive patients. DC supplementation has been hailed for its positive effects on cardiovascular health and it has been

Study Interventions
Dark Chocolate (85% cocoa), White/Milk chocolate (<35% cocoa)
Primary Endpoints
Soluble NOX2-derived peptides (sNOX2-dp)
Study Period
2017-09-25 → 2018-11-01
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. NAD+ is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 42044228) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

Related Compounds

Other Anti-Aging Research Compounds

Epitalon
Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mamma…
→
Humanin
BACKGROUND: Brain aging leads to structural changes, especially atrophy, which can result …
→
SS-31
Doxorubicin (DOX) is a widely used anticancer drug associated with severe cardiotoxicity p…
→
Thymulin
BACKGROUND: Development of neutralizing anti-factor [F]VIII antibodies (inhibitors) follow…
→
View all Anti-Aging compounds →