NAD+, short for nicotinamide adenine dinucleotide, is the oxidized form of NADH. It’s main biological function is to carry electrons from one biochemical reaction to another, acting to shuttle energy within a cell and, in certain conditions, to extracellular locations as well. NAD+ also plays roles in enzyme activation/deactivation, posttranslational modification of proteins, and cell-to-cell communication. As an extracellular signaling molecule, NAD+ has been found to be released from neurons in blood vessels, the bladder, the large intestine, and from certain neurons in the brain.


Anti-Aging Research and NAD+

One of the primary results of the standard aging process is a decline in both the quality and activity of mitochondria. Mitochondria are the body’s power plants, producing the energy for everything from neuron firing to digestion and muscle function. A decline in mitochondrial functioning has been associated with normal aging, but is also a factor in a number of age-related disease processes. Research shows that mitochondrial aging contributes to cellular senescence, inflammation, and even changes in stem cell activity that reduce rates of healing and make it harder for the body to recover from injury in old age.

The Role of NAD+ In Muscle Function

Another link between aging and NAD+ can be seen in skeletal muscle tissue. In mouse models, age-related muscle decline occurs in two steps. In the first step, oxidative phosphorylation (the process mitochondria use to produce energy) declines because of reduced expression of mitochondrial genes (mitochondria contain their own DNA). In the second step, genes regulating oxidative phosphorylation begin to malfunction in both the mitochondria and nucleus. Phase 1 is reversible. If NAD+ is administered, mice in these studies show improved mitochondrial function and do not progress to step 2. If, however, the mice are allowed to progress to stage 2 without intervention, then NAD+ cannot rescue them. This evidence suggests that intervention in mitochondrial aging is possible using NAD+, but that waiting too long results in refractory dysfunction. It is the best argument yet that early supplementation with NAD+ is critical to fighting off aging in the long term.

NAD+ in Neurodegenerative Disease

Much of what has been learned about NAD+ and the aging process is actually applicable to a number of disease conditions. In particular, changes in NAD+ appear to have far-reaching effects in the central nervous system and have been linked to a number of neurodegenerative diseases such as Alzheimer’s and Huntington’s diseases. A review article published in 2019 explained the current state of the knowledge as it relates to NAD+ and the central nervous system. In short, NAD+ is neuroprotective in a number of mouse models of human diseases such as Huntington’s disease. It appears that the cofactor is important in improving mitochondrial function, which in turn decreases the production of reactive oxygen species (ROS). ROS are known to cause damage in a number of inflammatory and disease conditions. They also accelerate the aging process. There is interest in a possible synergistic effect that could be gained through NAD+ supplementation in combination with a class of medications known as PARP inhibitors. PARP proteins are involved in DNA repair and programmed cell death. Though activated PARP is important to DNA repair, too much PARP activity can actually deplete cellular energy stores and induce programmed cell death.

The Role of NAD+ in Reducing Inflammation

NAD+ levels are regulated by a number of factors, one of which is NAMPT. This particular enzyme is known to be associated with inflammation and is often overexpressed by certain types of cancer. Researchers are, in fact, targeting NAMPT as a potential anti-cancer treatment. The regulator has also been linked to the development of obesity, type 2 diabetes, and nonalcoholic fatty liver disease. It is a potent activator of inflammation and its levels increase dramatically as NAD+ levels decrease. It is thought that supplementation with NAD+ can help to reduce NAMPT activation and thus modulate inflammation.

NAD+ in Addiction Treatment

It has long been known that drugs and alcohol can have a deleterious effect on NAD+ levels. This leads to nutritional deficits, but has also been linked to changes in mood and awareness. Supplementation with NAD+ to help overcome these deficits started in the 1960s, but has recently gained popularity as a result of studies showing that NAD+ in combination with specific amino acid complexes can actually boost recovery and lead to more profound and lasting results during addiction rehabilitation. Research indicates that the combination of NAD+ and certain amino acids can reduce cravings and improve stress and anxiety levels>.

NAD+ Supplementation and the Future of Aging Research

There is good evidence from animal models to suggest that NAD+ supplementation can offset some of the effects of mitochondrial aging. Much of this evidence, however, comes from animal models. There has been a strong push to test NAD+ in clinical trials of neurodegenerative disease and chronic type 2 diabetes. In both cases, the simple cofactor holds a great deal of promise for, at the very least, slowing the progression of these devastating diseases. There is even hope that NAD+ can, by itself or in combination with other therapies, reverse certain disease processes or even regulate the aging process itself.

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