Skip to main menu Skip to main content Skip to footer
NAD

You Might Also Like

»

What is NAD?

Nicotinamide adenine dinucleotide (NAD) is an important co-factor involved in numerous physiological processes, including metabolism, post-translational protein modification, and DNA repair. In living organisms, a careful balance between NAD production and degradation serves to regulate NAD levels. 

Recently, a number of studies have demonstrated that NAD levels decrease with age, and the deterioration of NAD metabolism promotes several aging-associated diseases, including metabolic and neurodegenerative diseases and various cancers. Research demonstrates that by the age of 50, a typical person may only have half the NAD+ levels they did in their youth. By age 80 these levels drop to only 1-10% of youth levels. 

Conversely, the upregulation of NAD metabolism, including dietary supplementation with NAD precursors, has been shown to prevent the decline of NAD and exhibits beneficial effects against aging and aging-associated diseases. In addition, many studies have demonstrated that genetic and/or nutritional activation of NAD metabolism can extend the lifespan of diverse organisms. Collectively, it is clear that NAD metabolism plays important roles in aging and longevity. In this review, we summarize the basic functions of the enzymes involved in NAD synthesis and degradation, as well as the outcomes of their dysregulation in various aging processes. In addition, a particular focus is given on the role of NAD metabolism in the longevity of various organisms, with a discussion of the remaining obstacles in this research field.

A single vial of NAD

Mechanism of Anti-Aging

  • NAD+ is required for functioning of sirtuins (proteins that contribute to longevity by maintaining the length of critical telomeres)
  • Telomeres are stretches of repetitive DNA strands that cap the ends of chromosomes. Every time the cell replicates, the telomeres at the end of that DNA strand shorten. Once telomeres reach a critical short length, cell renewal virtually halts, leading to accelerated aging or death of the cell. 
  • Telomere shortening is both a marker of cellular aging and a predictor of shortened lifespan
  • Even though DNA is protected by its chromosomal shelter, it is highly vulnerable to damage.
  • This can lead to broken DNA strands and mutations in crucial genes. Accumulated DNA damage contributes to the aging process and can result in specific lifespan-shortening diseases like cancer and poor immune function.
  • When DNA is damaged, it activates an enzyme known as PARP-1 that carries out DNA repair within cells.19 To carry out its function, PARP-1 consumes enormous amounts of NAD+. As NAD+ is depleted, the ability of PARP-1 to repair DNA is significantly hindered.
  • The good news is that replenishing NAD+ to cells can restore DNA repair and prevent cell death under stress.26,29 In two different animal models of neurodegenerative disease, increasing cellular NAD+ reduced the severity of the disorder, normalized neuromuscular function, delayed memory loss, and extended lifespan.
  • Conclusion: Improving DNA repair with NAD+ may slow cellular aging, reduce the persistence of cancer-causing mutations, and play an important role in preventing inflammatory conditions such as atherosclerosis.
  • A universal feature of aging is the loss of cellular energy, which results in diminished ATP levels and inadequate cellular fuel necessary to power your body.
  • One cause of this energy loss is a breakdown in the efficiency of the electron transport chain, the main pathway through which we extract energy from food (and of which NAD+ is an essential component).Disorders ranging from obesity and diabetes to bone loss have been associated with loss of this vital pathway. 
  • Studies now show that restoring electron transport chain function by raising levels of NAD+ is a rapid and efficient means of promoting the essential enzymes involved in energy extraction and sustaining youthful cell function. This helps to reduce physiological decline and provides protection from age-related disease.
  • Conclusion: Improving the energy-extraction process in all cells with NAD+ increases their capacity to do the work they are specialized for. It also protects mitochondria from early death, a benefit that is associated with reduced cellular aging and lowered risks for cardiovascular and brain disease.
  • A universal feature of aging is the loss of cellular energy, which results in diminished ATP levels and inadequate cellular fuel necessary to power your body.
  • One cause of this energy loss is a breakdown in the efficiency of the electron transport chain, the main pathway through which we extract energy from food (and of which NAD+ is an essential component). Disorders ranging from obesity and diabetes to bone loss have been associated with loss of this vital pathway.
  • Studies now show that restoring electron transport chain function by raising levels of NAD+ is a rapid and efficient means of promoting the essential enzymes involved in energy extraction and sustaining youthful cell function. This helps to reduce physiological decline and provides protection from age-related disease
  • Conclusion: Improving the energy-extraction process in all cells with NAD+ increases their capacity to do the work they are specialized for. It also protects mitochondria from early death, a benefit that is associated with reduced cellular aging and lowered risks for cardiovascular and brain disease.
  • Our chromosomes are complex structures housing our DNA. Access to DNA strands for “reading out” genetic instructions requires biochemical control of those proteins to make sure each gene functions properly
  • But like any complex molecular structure, chromosomes can become unstable. Eventually, this triggers errors in the ways our genes are interpreted—which ultimately contributes to deleterious changes in cell function and structure. Aging is accelerated in the presence of increased chromosome instability
  • The enzymes involved in sustaining stable chromosomal structures require NAD+ in order to function properly.
  • In animal models showing that NAD+ contributes to longevity, a major factor has been shown to be sufficient availability of the nutrient. And studies show that when enzymes that require NAD+ are inactive, chromosome structure suffers and cells replicate abnormally.
  • Conclusion: NAD+ supplementation is a promising cutting-edge strategy to improve chromosome stability, a treatment that may slow down cellular aging (senescence) and lower the risk of cancer.
  • Neurotransmitters are brain chemicals that relay signals between nerve cells. In doing so, they help regulate body-wide functions such as mood, appetite, and stress.
  • NAD+ has been found to meet all criteria for a neurotransmitter.
  • Evidence for NAD+’s neurotransmitter function has now been found in intestinal and blood vessel smooth muscles, as well as in the brain itself.
  • Conclusion: Ample NAD+ nutrition appears essential for sustaining brain health.
  • Proteins called sirtuins are major regulators of cellular aging because they influence fundamental functions such as DNA repair and inflammatory responses. They also influence whether cells enter a replicative cycle or instead die a programmed death (apoptosis)
  • Compounds that activate sirtuins are eagerly sought as chemical “fountains of youth.” Familiar supplements like resveratrol and quercetin have been evaluated as promising sirtuin activators.
  • NAD+ is required for sirtuins to function.
  • Conclusion: Sirtuin activation has shown great promise in fighting cardiovascular disease and preserving aging brain function, but these longevity-promoters cannot function without sufficient NAD+.
  • NAD+ was first discovered as an important part of the process that channels chemical energy from foods to the ATP fuel our cells require. Recent studies have revealed that NAD+ is itself a form of “energy currency” similar to ATP.
  • NAD+ is also a functional signaling molecule in processes related to energy production, including PARP-1 and sirtuins. When DNA damage occurs, PARP-1 consumes large quantities of NAD+, leading to reduced energy production. In addition, high levels of NAD+ can activate sirtuins, permitting them to carry out their metabolic and stress-protective responses and contributing to longevity. 
  • Conclusion: Supporting efficient energy production and adequate ATP levels requires consistent and abundant NAD+. This is critical because waning energy supplies contribute to the aging process.

Metabolic Benefits of Boosting NAD+

Nicotinamide riboside boosts NAD+ and appears useful in preventing diseases associated with abnormal energy utilization. These include obesity, diabetes, and atherosclerosis, which are components of metabolic syndrome.

A mouse study revealed that prediabetic mice given nicotinamide riboside have better glucose tolerance, less weight gain and liver damage, and slower development of fatty livers. Similarly, in diabetic mice, nicotinamide riboside markedly reduced blood sugar, weight gain, and liver fat, while also preventing diabetic nerve damage.

Nicotinamide riboside is especially beneficial in combatting nonalcoholic fatty liver disease (NAFLD), which is considered the liver manifestation of metabolic syndrome. Interventions that reduce NAFLD generally improve all-around metabolic health. Studies in animal models of NAFLD have shown that nicotinamide riboside supplementation corrects biochemical and microscopic liver changes in mice fed a high-fat diet. In another study of obesity induced by a high-fat diet, supplementation with nicotinamide riboside increased NAD+ levels, activated sirtuins, and protected against the oxidative stresses and other damage induced by the diet (many of NAD+’s longevity mechanisms mentioned above).

Routes of Administration for NAD+ Treatment

  • Intravenous
  • Oral 
  • Topical 
  • Nasal 

Potential Side Effects

  • Flushing and warm sensation 
  • Nausea and GI disturbances
  • Headache 
  • Dizziness
  • Lightheadedness
⇧