NAD+

Introduction – What is NAD+?

NAD+ (Nicotinamide Adenine Dinucleotide) is a vital coenzyme found in all living cells, playing a crucial role in cellular metabolism and energy production. Structurally, NAD+ consists of two nucleotides joined through their phosphate groups, with one nucleotide containing an adenine base and the other a nicotinamide base. Functionally, NAD+ is essential in redox reactions, acting as an electron carrier. It cycles between its oxidized form (NAD+), which can accept electrons, and its reduced form (NADH), which carries and donates electrons to other molecules. This electron transfer is fundamental in cellular respiration processes like glycolysis, the citric acid cycle, and oxidative phosphorylation, all of which generate ATP, the primary energy currency of cells. Beyond energy production, NAD+ is involved in DNA repair, gene expression regulation, and maintaining genome integrity. It also activates sirtuins, a family of proteins linked to aging, inflammation, and stress resistance.

Biologically, NAD+ is crucial for converting nutrients into energy and ensuring cellular health. Its levels naturally decline with age and boosting NAD+ has been associated with improved health span and lifespan in various organisms. Adequate NAD+ levels are necessary for optimal cell function and survival. Given its significance, NAD+ precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have become popular dietary supplements. Ongoing research aims to understand how increasing NAD+ levels can affect aging and age-related diseases, highlighting its potential in promoting healthy aging and optimal cellular function.

What happens when NAD+ levels are low?

When NAD+ levels are low, several adverse effects can occur due to its essential role in cellular processes. One of the primary consequences is a decline in cellular energy production, as NAD+ is crucial for converting nutrients into ATP, the cell’s main energy currency. This energy deficit can lead to increased fatigue, reduced physical performance, and general lethargy. Additionally, low NAD+ levels impair the function of sirtuins, proteins that regulate inflammation, stress resistance, and cellular repair. This impairment can accelerate aging and increase susceptibility to age-related diseases.

Furthermore, insufficient NAD+ hinders DNA repair processes, leading to genomic instability and a higher risk of mutations and cancers. The decline in NAD+ also affects mitochondrial function, potentially resulting in neurodegenerative diseases and cognitive decline due to reduced brain cell protection and maintenance. Metabolic health can be compromised as well, increasing the risk of conditions such as obesity, diabetes, and cardiovascular diseases. Overall, maintaining adequate NAD+ levels is crucial for sustaining energy production, cellular health, and longevity, and its deficiency can have wide-ranging negative impacts on overall health and well-being.

NAD+ is the second most abundant cofactor in the human body. Anti-aging therapies are becoming more mainstream as aging is now more often being viewed as a disease. Now that this transition is happening, the ability for NAD+ to activate PARPS, Sirtuins, and help with immune dysregulation has been thoroughly investigated and NAD+ and its precursors have been highly popularized. The clinical importance of maintaining cellular NAD+ levels was established early in the last century with the finding that pellagra, a disease characterized by diarrhea, dermatitis, dementia and death, could be cured with foods containing the NAD+ precursor niacin.

Additionally, cellular concentrations of NAD+ have been shown to decrease under conditions of increased oxidative damage such as occur during aging Altered levels of NAD+ have been found to accompany several disorders associated with increased oxidative/free radical damage including diabetes, heart disease, age-related vascular dysfunction, ischemic brain injury, misfolded neuronal proteins, and Alzheimer’s dementia. Interventions targeted at restoring NAD+ has been shown in animal models to support healthy aging and improve metabolic function, and dementia.

A need for NAD+ in muscle development, homeostasis, and aging

In a review study, researchers discuss the recent data that document conserved roles for NAD+ in skeletal muscle development, regeneration, aging, and disease as well as interventions targeting skeletal muscle and affecting NAD+ that suggest promising therapeutic benefits. The researchers also highlight gaps in our knowledge and propose avenues of future investigation to better understand why and how NAD+ regulates skeletal muscle biology.