Why Does NAD Matter?
Updated: Feb 7
NAD+ could hardly be more important. It is the central regulator of metabolism.
What NAD Does
NAD+ is essential to the transfer of cellular energy, and also is directly used by enzymes like PARPs and sirtuins that manage other important cellular processes. If you don't have enough NAD, it causes a lot of problems, including the kind we associate with aging:
NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response through these enzymes. Numerous studies have shown that NAD levels decrease with aging and under disturbed nutrient conditions, such as obesity. Additionally, a decline in NAD levels is closely related to the development of various metabolic disorders, including diabetes and fatty liver disease...
NAD+ influences cellular health in many important ways, including aging, DNA repair, epigentic regulation, circadian rhythms, sexual reproduction, autophagy, and metabolic energy balance.
[NAD+ affects] an extensive suite of processes, including: DNA repair, central metabolism, circadian rhythms, meiosis and lifespan. Owing to its centrality in cellular homeostasis, defects in NAD+ metabolism are often associated with a variety of disease states, seen in diabetes, neurological disorders, and various cancers.
NAD+ levels have important biological functions in aging. During aging, the declined cellular NAD+ level can affect DNA repair, epigenetic regulation, autophagy, and redox balance. Because NAD+ is a cofactor for various enzymes, loss of NAD+ impacts many cellular processes. For example, NAD+ is required for the activity of epigenetic regulators such as histone deacetylase SIRT1, and a decline in its level causes changes in histone acetylation, which subsequently influences chromatin organization and gene expression. NAD+ is also required for DNA repair via PARPs during aging, and the decline of NAD+ could cause DNA damage accumulation. Autophagy is regulated by NAD+ levels via sirtuins (mostly SIRT1). The decline of NAD+ levels reduces overall autophagy. Moreover, NAD+ is an important coenzyme in redox reactions. The NAD+/NADH redox balance is required for metabolic homeostasis.
Since NAD+ levels can directly and indirectly impact a number of metabolic functions regulated by enzymes whose activity depends on NAD+, changes in intracellular NAD+ levels affect all the processes regulated by these enzymes, which include cellular metabolism, gene expression regulation, DNA repair, mitochondrial functions, redox reactions, inflammation, intracellular trafficking, aging, and cell death. Therefore, many pathological conditions are associated with an impairment of intracellular NAD+ levels, including cardiovascular diseases, cancer, obesity, neurodegenerative diseases, and aging.
-- Antioxidants, February 4, 2023
If you DNA is damaged, NAD gets used up quickly as part of the repair process. And if NAD is aggressively routed to DNA repair, then there will be a severe limitation of NAD+ availability for other functions.
It has been demonstrated that extensive DNA breaking can dramatically reduce intracellular NAD+ content up to 20–30% of its normal level, resulting in severe limitation of NAD+ availability for other NAD+-dependent enzymes.
-- Antioxidants, February 4, 2023
Not only does NAD+ plays a unique role in DNA repair, epigenetic control, and immune activation, but may also be implicated in treating degenerative diseases:
Maintenance of intracellular NAD+ levels is pivotal for the regulation of DNA repair, stress resistance, and cell death...Agents such as NR, and to a lesser degree, NA and NAM, can protect severed axons from degeneration, and extend life span in small organisms...
NAD Levels and the Immune System
Not just degenerative diseases, but also infectious diseases. Some pathogens take down the host's immune defenses by attacking the NAD system:
Interestingly, several pathogens also appear to target the NAD+ metabolic network upon infection including Mycobacterium tuberculosis [tuberculosis], Aspergillus fumigatus [fungal infection], Toxoplasma gondii [toxoplasmosis], SARS-CoV-2 (COVID-19), and HIV [AIDS]..NAD+ levels also appear to decline with age, which may render the elderly more susceptible to various infections as well as age-associated disorders...
NAD Levels and Non-Infectious Diseases
And it's not just diseases that lower your NAD levels. Reduced NAD levels, can cause and/or result from all kinds of physical disorders, like obesity, diabetes, neuropathy, kidney and liver diseases, aging, and cancer. And restoring NAD levels can help:
Aberrant NAD+ metabolism, which causes substantial metabolic stress, has been implicated in diverse disorders ranging from obesity, diabetes, neuronal degeneration, kidney diseases, fatty liver disease and cancers. NAD+ preservation (or enhanced NAD+ homeostasis) is also shown to alleviate age-associated functional decline and/or extend life span in various model systems
NAD Levels and Neurodegenerative Diseases
In addition, many degenerative nerve disorders, such as Alzheimer's disease, Parkinson's disease, Ataxia, and ALS involve axon disintegration. It appears that in these neurodegenerative disorders, something in the metabolic chain of events causes NAD depletion, and when the axons run out of NAD they die:
Axonal degeneration (Wallerian degeneration) is seen in many disorders in the nervous system including Alzheimers’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). The discovery of the slow Wallerian degeneration mutant mouse (Wld s) immediately linked NAD+ biosynthesis enzymes, NMNATs, with disease of the nervous system...Regarding the cause of neuronal death...it is well-supported that NAD+ depletion is the common factor...[emphasis added]
NAD is essential for cells to do what they do. When cells run low on NAD, they can't function properly. When they entirely run out of NAD, they die. Whether, when, and how best cellular function can be restored by replenishing NAD is what scientists are trying to determine right now, and what this website is documenting.
Read more about What Is NAD?