Nicotinamide Adenine Dinucleotide (NAD+) is the newest powerhouse nutrient in the fight against age for cellular processes, DNA repair, and regulation of gene expression. It is now widely recognized by researchers that NAD+ is a crucial player in longevity and the treatment of diseases in aging. This in-depth guide explores the biology of NAD+ and its relevance to human health.

Understanding Nicotinamide Adenine Dinucleotide (NAD+)

Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme present in all living cells. Just like Nicotinic acid, the pro-vitamin, NAD+ exists as an oxidized (NAD+) and a reduced (NADH) form: It is well known that NAD+ plays a central role in cellular metabolism, as it is essential for a large number of oxidation-reduction reactions catalyzed by different NAD+-dependent enzymes. Oxidation-reduction reactions are vital to all lifeforms, especially because they generate the energy we need for our survival, with most of the energy stored in food eventually released via such reactions.

The Role of NAD+ in Longevity

An increasing amount of data supports a strong link between NAD+ levels and longevity. Levels drop off with age. That is partly why cells age and become more prone to diseases. Cells start following the wrong pathways and developing inflammation. Restoring it – whether through supplements or activation of the biosynthesis pathway – can reverse this and help people live longer.

NAD+ increasing longevity

NAD+ and Age-Related Diseases

Age-related pathologies often promote an underlying cellular dysfunction, and some of the common diseases of aging – such as cardiovascular disease, neurodegeneration, and metabolic syndromes – seem to progress by a process of cellular deterioration fueled by NAD+ depletion, through mechanisms including poor mitochondrial function, DNA repair defects and unwanted inflammation. With new directions to explore, intervention strategies based around NAD+ are therefore poised to become a novel therapeutic tool in the fight against age-related disease.

The Link Between NAD+ and DNA Repair

DNA repair. An accumulation of DNA damage, the most essential aspect of the development of senescence, is one of the main reasons we get old, and suffer from age-related pathologies. NAD+ is a cofactor in these DNA repair processes, so it is what keeps the enzymes that patrol our genome – namely, poly-ADP-ribose polymerases (PARPs) and sirtuins – running. PARPs are protein regulators that contribute to genetic stability by repairing damaged DNA strands, thus preventing the accumulation of the mutations that result in senescence and age-related disease.

NAD+ Precursors and Supplements

To increase NAD+ levels, scientists have studied many different precursors and supplements. Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN) are two of the most-researched NAD+ precursors – compounds that can both enter cells and stimulate NAD+ biosynthesis, increasing NAD+ levels in cells and tissues. Many supplements are used by consumers because they have NAD+ precursors like NR and NMN, or NAD+ activators such as resveratrol and quercetin. These supplements are used for their potential anti-aging effects.

Old couple exercising to increase NAD+ levels

Regulation of NAD+ Biosynthesis Pathways

NAD+ biosynthesis is a tightly governed process and occurs through the coordination of a multitude of enzymes and signaling pathways. The NAD+ salvage pathway involving the use of precursors such as NR and NMN, together with the de novo synthesis pathway, controls cellular NAD+ levels. Caloric restriction, exercise, and/or pharmacological inhibition of de novo synthesis of NAD+ can all be used to modulate NAD+ biosynthesis pathways, holding promise for longevity and healthy aging.

Clinical Implications and Future Directions

This suggests that NAD+ could be a promising target for anti-aging interventions and has instigated a good deal of translational research and clinical trials in the past few years. Cancer drug trials with mRNA (messenger ribose nucleic acid) and an NAD+ nicotinamide activation trial for Parkinson’s Disease have completed clinical phases in humans, showing encouraging first results for longevity-promoting outcomes in age-related diseases. Though much is still unknown about the scope and mechanism of NAD+, future studies will shed light and advance resilience-promoting targets toward increasing longevity and healthy trajectories of aging.

Frequently Asked Questions (FAQs)

Q1: Can NAD+ supplementation reverse aging?

A1: NAD+ supplementation now shows promise to alleviate some age-related decline. Whether it can reverse aging is still an open research question. So far, there are indications that precursors and activators of NAD+ can improve aspects of aging. However, the extent to which they would affect longevity and health more generally is still a mystery.

Q2: Are there any side effects associated with NAD+ supplementation? 

A2: Adequate trials have not been performed to figure out whether NAD+ supplementation has significant side effects, but irritation of the gastrointestinal tract and allergic responses to individual amino acids have been reported. Before supplementation with NAD+ or any other dietary supplement, you should always seek advice from a healthcare professional. In case of a pre-existing medical condition, it is particularly important to consult your doctor.

Q3: How can I naturally increase NAD+ levels? 

A3: Physical activity, calorie restriction, and sufficient sleep all encourage upregulation of the NAD+ biosynthesis pathways. Food-derived NAD+ precursors, such as lactose found in dairy products, creatine found in fish, and tryptophan found in nuts also aid in supporting the level of NAD+.

Q4: Is NAD+ involved in the regulation of circadian rhythms? 

A4: Yes, NAD+ is integral to ‘circadian homeostasis’, which refers to the family of processes that regulate sleep-wake cycles, metabolism, and other physiological activities on a 24-hour schedule. Interference to the metabolism of NAD+ has been implicated in circadian rhythm disorders and related conditions.

Q5: Can NAD+ supplementation improve cognitive function?

A5: There is increasing evidence to prove that NAD+ supplementation can improve cognitive function in aging humans by enhancing mitochondria function and retaining other essential mechanisms responsible for DNA repair in neurons. NAD+ precursors and activators could be valuable interventions for age-related cognitive decline.


NAD+ is one of the most studied molecules for aging and aging-related diseases. As NAD+ mechanistic and therapeutic potential continues to be unraveled in the coming years, we suggest that it could stand as one of the most important targets for improving human health span and longevity.

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