Nicotinamide Adenine Dinucleotide (NAD): Difference between revisions

Nicotinamide Adenine Dinucleotide (NAD) (view source)

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 * The effective dosages and potential side effects.
 * The real impact on human longevity.
-==NAD+ and Aging-Related Enzymes==
+== NAD+ and Its Role in Aging ==
-Nicotinamide adenine dinucleotide (NAD+) is a key coenzyme in metabolic processes, playing roles in energy expenditure, metabolic and stress adaptations, and circadian rhythm maintenance. A significant decline in NAD+ levels with age can be attributed to CD38, an enzyme responsible for NAD+ degradation, disrupting NAD+ synthesis pathways during aging{{pmid|27304496}}. NAD+ homeostasis is critical for optimal biological function, with NAD+ consuming enzymes playing specific roles in biological aging. They are potential targets for geroprotection, including CD38, the sirtuins (SIRT) deacetylases, poly [ADP-ribose] polymerase 1 (PARP1, involved in DNA damage response), and the neuronal degenerating factor SARM1{{pmid|28676700}}{{pmid|25908823}}.
+Nicotinamide adenine dinucleotide (NAD+) is a crucial molecule in our bodies, involved in turning nutrients into energy, adapting to stress, and maintaining our daily biological rhythms. As we age, the amount of NAD+ in our bodies decreases. This is partly due to the action of an enzyme called CD38, which breaks down NAD+, leading to lower levels in older individuals{{pmid|27304496}}. Keeping a balance of NAD+ is important for our cells to work properly, and enzymes that use NAD+ are being studied for their potential to slow down aging processes. These enzymes include CD38, sirtuins (SIRT), which are involved in cell regulation, PARP1, important for DNA repair, and SARM1, linked to nerve cell health{{pmid|28676700}}{{pmid|25908823}}.
+Our bodies can make NAD+ in two ways: either from scratch using certain nutrients like nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), or by recycling components from chemical reactions in our cells{{pmid|32694684}}. An enzyme on the surface of our cells, called CD73, also helps to keep NAD+ levels up by converting NMN to NR{{pmid|32389638}}.
+=== The Role of NNMT in NAD+ Levels ===
+An enzyme named nicotinamide N-methyltransferase (NNMT) plays a key role in managing NAD+ levels. It changes nicotinamide, a form of vitamin B3, into a substance called methylnicotinamide (MNT). This change affects how much nicotinamide is available to make NAD+ in our cells. NNMT is linked to conditions like obesity and type two diabetes{{pmid|29483571}}. Interestingly, NNMT also helps stabilize SIRT1, an enzyme that protects cells from stress and can increase lifespan{{pmid|34153425}}{{pmid|26168293}}{{pmid|24077178}}. Researchers are looking into NNMT inhibitors as potential treatments for diseases like cancer, obesity, and liver diseases related to alcohol use{{pmid|29483571}}{{pmid|34704059}}{{pmid|34572571}}{{pmid|29155147}}{{pmid|34424711}}. The balance between NNMT, MNT, and NAD+ is important for our health, especially as we age.
-NAD+ can be synthesized de novo from nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), or salvaged through the NAD+ salvage pathway, crucial for recycling metabolites to replete NAD+ stores{{pmid|32694684}}. An extracellular conversion of NMN to NR by CD73, a cell surface enzyme, also helps maintain intracellular NAD+ content{{pmid|32389638}}.
-===Nicotinamide N-Methyltransferase (NNMT) and Its Role===
-Nicotinamide N-methyltransferase (NNMT) regulates cellular NAD+ levels by methylating nicotinamide into methylnicotinamide (MNT), reducing free nicotinamide availability for NAD+ conversion through the NAD+ salvage pathway. NNMT and MNT are associated with conditions like obesity and type two diabetes mellitus{{pmid|29483571}}. Interestingly, NNMT stabilizes SIRT1, offering metabolic benefits and protection against oxidative stress-induced cellular injury{{pmid|34153425}}{{pmid|26168293}}. Methylnicotinamide has been shown to increase lifespan{{pmid|24077178}}. Furthermore, various NNMT inhibitors have been developed, showing potential in treating pathological states like cancer, metabolic disorders, and alcohol-related fatty liver disease{{pmid|29483571}}{{pmid|34704059}}{{pmid|34572571}}{{pmid|29155147}}{{pmid|34424711}}. The interaction between NNMT, MNT, and their regulatory pathways plays a significant role in NAD+ homeostasis and the complex disease states affecting the aging process.
 == NAD+, Sirtuins and Longevity-Promoting Pathway ==
 [[File:CD38-NAD+-SIRT1 Axis.png|thumb|The CD38/NAD+/SIRT1 Axis. NAD+ levels in the body can be influenced by the supplementation of precursors nicotinamide (NAM), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). NAD+ levels decrease with age and are further metabolized by the activation of SIRT1, PARP1, SARM1, and CD38. Restoring NAD+ levels allows for an increase in SIRT1 activity due to increased substrate availability, resulting in the inhibition of age-promoting pathways and activation of adaptive and protective transcription factors and processes. The central lineage may be described as the CD38/NAD+/SIRT1 axis, and targeting this access with nutraceutical interventions may prevent the age-related decline of NAD+ levels in the body. Black lines indicate conversion or activation. Red lines indicate inhibitors or destroyers of the indicated target.{{pmid|36678315}}|450x450px]]