Nicotinamide adenine dinucleotide, or short NAD+, is an oxidized form of NADH. This coenzyme is present in all living cells and plays a significant role in metabolism and energy production. NAD+ is important for metabolic processes since it's involved in redox reactions.
It serves as a significant electron transporter in the ETC or mitochondrial electron transport chain, producing ATP or cells' energy currency. As cells age, NAD+ levels decrease, which has been linked to age-related cellular damage and metabolic dysregulation.
NAD+ Research
NAD+ and Anti-Aging
As previously mentioned, one of the main results of the standard aging process is a decline in both the activity and quality of mitochondria, which are the body's power plants. They generate energy for everything from digestion and muscle function to neuron firing.
While the decline in mitochondrial function has been associated with regular aging, it's also a factor in several age-related disease conditions. New research on animal models found that some age-related decline observed in mitochondria can be reversed through NDA+ dietary supplementation.
David Sinclair, who worked at Harvard University and discovered the anti-aging effects of resveratrol, a component in red wine, also uncovered that mitochondria in mice muscle could be rejuvenated by injecting a precursor to NDA+.
Research conducted in 2013 proved that declining levels of NDA+ led to a pseudohypoxic state within cells. This interrupts the normal signaling between the nucleus, where DNA resides, and the mitochondria. By giving old mice NDA+, mitochondrial function and communication are restored.
Muscle Function
Another connection between NAD+ and aging can be noticed in skeletal muscle tissue. In laboratory settings, a study was conducted on mice, and scientists discovered that age-related muscle decline happens in two steps. In the first step, the mitochondria’s energy production process, called oxidative phosphorylation, slows down because the expression of their own genes drops. (Yes, mitochondria have their own DNA!)
During the second step, genes that regulate oxidative phosphorylation malfunction in the nucleus and mitochondria. Phase one is reversible. If NDA+ is administered, mice that were involved in this study showed significant improvement in mitochondrial function and didn't progress to step two. But, if mice progressed to stage two without intervention, NDA+ could not rescue them.
Neurodegenerative disease
Changes happening in NAD+ seem to have far-reaching effects on the central nervous system and have been connected to several neurodegenerative diseases, like Huntington's and Alzheimer's diseases. According to studies conducted on mice, NAD+ acts as a neuroprotective in a few mouse models of human diseases like Huntington's disease.
It appears that the cofactor is crucial in boosting mitochondrial function, which in turn lowers the production of ROS or reactive oxygen species. ROS can cause damage to a number of diseases and inflammatory conditions. They also speed up the aging process.
NAD+, when combined with PARP inhibitors, which are proteins involved in DNA repair, can cause a significant improvement in neurodegenerative conditions.
When it comes to Parkinson's disease, it has been shown in animal models that NDA+ supplementation can help protect against the death of dopaminergic neurons and motor deficits.
Reducing inflammation
Several factors regulate NAD+ levels, one of which is NAMPT. This particular enzyme is linked to inflammation and is often overexpressed by certain types of cancer. Scientists discovered that targeting NAMPT could be a potential anti-cancer treatment in animal settings. It has been connected to the development of type 2 diabetes, obesity, and non-alcoholic fatty liver disease. NAMPT can activate inflammation, and its levels increase as NAD+ levels lower.
Some believe that administering NAD+ can reduce NAMPT and regulate inflammation. After conducting studies on rats, good evidence indicates that NAMPT/NAD+ dichotomy is the main reason for the insulin resistance associated with heart disease and obesity.
It seems that obesity could cause inflammation and lead to an overall reduction of NAD+ levels, which in turn boosts free fatty acid levels in the blood. In this case, the liver will produce more glucose, and the result is insulin resistance, which the pancreas tries to overcome by producing more insulin.
Addiction treatment
We all know that alcohol and drugs have a harmful effect on NAD+ levels, leading to nutritional deficits. It has also been associated with changes in awareness and mood. When administered in animal models, NAD+ was successful in overcoming these deficits.
It all started with research in the 1960s but recently has gained in popularity as a result of studies indicating that NAD+ in combination with particular amino acid complexes can enhance recovery and lead to more long-lasting results in addiction recovery.
Summary
NAD+ (nicotinamide adenine dinucleotide) is an indispensable coenzyme that functions in the energy and metabolic pathways. It acts as an electron carrier in the mitochondrial electron transport chain, transferring electrons to oxygen molecules to produce ATP. Its natural presence decreases together with aging. Its low supply of NAD+ is likely to be responsible for the development of diseases - an increased oxidative reaction, a disorder of the metabolic state, and age-related diseases in cells.
Consequently, it is suggested by the latest research that the steady jump in NAD+ can reverse mitochondrial damage, fix muscle malfunction, and also, improve the communication between the nucleus and the mitochondria. Also, it has proven to be effective in scientific research as a neuroprotective that reduces oxidative stress and inflammation in conditions linked to movement disorders like Alzheimer’s, Huntington’s or Parkinson’s diseases.
On another note, it is said that it may be used to manage the inflammation, resulting from being overweight as well as an associated issue such as diabetes and heart disease. Incidentally, it has helped addicts improve their recovery. It’s important to mention that all these findings are based on animal models and we need more research to fully confirm these claims.
References:
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- Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L, White JP, Teodoro JS, Wrann CD, Hubbard BP, Mercken EM, Palmeira CM, de Cabo R, Rolo AP, Turner N, Bell EL, Sinclair DA. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013 Dec 19;155(7):1624-38. doi: 10.1016/j.cell.2013.11.037. PMID: 24360282; PMCID: PMC4076149.
- Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014 Aug;24(8):464-71. doi: 10.1016/j.tcb.2014.04.002. Epub 2014 Apr 29. PMID: 24786309; PMCID: PMC4112140.
- Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels. Rejuvenation Res. 2014 Feb;17(1):62-9. doi: 10.1089/rej.2014.1546. PMID: 24410488.
- Ringholm S, Olesen J, Pedersen JT, Brandt CT, Halling JF, Hellsten Y, Prats C, Pilegaard H. Effect of lifelong resveratrol supplementation and exercise training on skeletal muscle oxidative capacity in aging mice; impact of PGC-1α. Exp Gerontol. 2013 Nov;48(11):1311-8. doi: 10.1016/j.exger.2013.08.012. Epub 2013 Aug 29. PMID: 23994519.
- Lloret A, Beal MF. PGC-1α, Sirtuins and PARPs in Huntington's Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochem Res. 2019 Oct;44(10):2423-2434. doi: 10.1007/s11064-019-02809-1. Epub 2019 May 7. PMID: 31065944.
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