Could NAD+ Be The Golden Ticket To Anti-Aging?

Research suggests that scientists may be close to finding that golden ticket to help us, this golden nucleotide is called nicotinamide adenine dinucleotide (NAD), and it plays a central role in aging.

NAD is found in all living cells, this helper molecule is a coenzyme that helps other enzymes complete their activities, and it is involved in cellular metabolism chemical reactions that sustain life.

Nicotinamide adenine dinucleotide exists in two forms: NAD+ and NADH because it is an electron carrier. In redox reactions one reagent transfers electrons to another while the other loses or is oxidized; in the case of NAD, NAD+ is reduced by accepting 2 electrons and a hydrogen atoms to become NADH.

Cells would not be able to stay alive without NAD+, think of it as a courier transporting electron goods to mitochondria factories; this shuffling helps enzymes to complete their duties.

NAD+ was initially thought to only be associated with cellular respiration, but now we know it goes beyond redox reactions to such as acting as a cosubstrate for three classes of enzymes that play key roles in maintaining cellular balance: 1) Sirtuins(SIRTS) the longevity gene; 2) ADP ribose transferases(ARTs) and poly(ADP-ribose) polymerases(PARPDs); and 3) cyclic ADP- ribose (cADRP) synthases (CD38 and CD157).

These enzymes rely on NAD+ to function, indicating that NAD+ plays a key role in biological processes such as DNA transcription, DNA repair, fatty acid synthesis, increasing energy production and utilization, coordinating circadian rhythms, regulation of protein-protein interaction, and new roles are still being discovered.

NAD+ levels decline with age, and low levels are thought to correlate with declining health which includes but is not limited to cognitive decline, fatigue, cancer, cardiovascular diseases, and disruptions in sleep cycle. Why levels of NAD+ decrease with age isn’t fully understood, but it is closely correlated with mitochondria health which is the powerhouse of the cell and a hallmark of aging.

As you read, write, watch tv, or look at a painting brain cells work to process the information through a series of signals. There are typically 86 billion neurons with 100 trillion interconnections in the human brain that provide physical basis for numerous capabilities such as processing images as quickly as blinking an eye.

This unparalleled processing ability is powered by the mitochondria through cellular respiration which breaks down food chemically to generate adenosine triphosphate energy currency for cells. To complete their functions estimates are that the body uses 160kg of ATP a day. Cellular respiration happens in four stages: glycolysis, pyruvate oxidation, citric acid cycle, and oxidative phosphorylation. Once this process is complete and all of the energy has been taken from food cells are able to store it for all of their activities.

There are 9 hallmarks of aging: genomic instability; mitochondrial dysfunction; stem cell exhaustion; altered intercellular communication; telomere attrition; deregulated nutrient sensing; loss of proteostasis; cellular senescence; and epigenetic alterations.

Mitochondrial health is thought to be one of the drivers of aging because they begin to lose function with age leading to disruption of homeostasis and eventually to a wide range of disease.

Accumulation of reactive oxygen species and mutations in mitochondrial DNA were initially believed to be the primary reasons for mitochondrial dysfunction;some now believe it is the decline in NAD+ levels which prevent mitochondria from producing ATP efficiently.

NAD+ is consumed and degraded by enzymes that depend on it to function, however the body does not have an endless supply of NAD+. There are several ways the body makes and maintains NAD+  including through precursors from which NAD+ can be synthesized.

Sirtuin proteins regulate biological functions important to aging such as DNA repair, cell cycle, inflammatory response, mitochondrial functions, maintenance of telomere length, DNA transcription, and apoptosis. Sirtuins have been dubbed the guardians of the genome, however they cannot function without NAD+: when levels are high sirtuins are more active and when low activities decline leading to aging.

The brain consumes more energy than any other organ in the body, meaning neurons depend on mitochondria to carry out their functions, this dependence also means mitochondrial dysfunction can contribute to neurodegenerative diseases; supplementation with NAD+ precursors or NADH has been shown to have neuroprotective properties.

SIRT3 protects cells from ROS that are a byproduct of oxidative phosphorylation, and it activates superoxide dismutase 2 scavenger enzymes that detoxifies ROS from cells.

New research suggests that NAD+ may promote development of some cancers as high levels can alter the NAD+/NADH ratio to disrupt cellular homeostasis and promote cancer; inhibiting NAMPT may suppress development of cancer, slow down cancer progression, improve patient survival, increase apoptosis, initiate cell death, and sensitize cancer cells to chemotherapy agents. Anti-aging health benefits may become clouded by possible roles in promoting cancer cell growth, however more research is needed to fully understand the role(s) NAD+ may play in cancer because reports of higher than normal levels being seen in cancer doesn't prove that it actually promotes cancer. 

Mounting evidence suggests that oxidative damage and mitochondrial dysfunction may contribute to the development of fibromyalgia and chronic fatigue syndrome, as patients with these disorders have low ATP levels; replenishment of NAD+ is believed to help trigger increased ATP regeneration and increase energy.

You can boost levels of NAD+ by consuming precursors found in rice, milk, flour, fish, beer, chicken, yeast, green vegetables, crimini mushrooms, and fermented foods like kombucha and sauerkraut.

Intermittent fasting can help to increase sirtuin levels which can redirect cellular energy towards maintaining homeostasis and exhibit anticancer effects.

Ketones may have antioxidant properties and they are an alternative fuel for the brain which have been shown to increase the brain NAD+/NADH ratio suggesting nutritional ketosis may help to preserve brain health.

With regular exercise the body burns NADH for energy and produces more NAD+. Exercise also increases activity of sirtuins and levels of NAMPT which correlates with better mitochondrial function.

Vitamin B3 and NAD+ precursor supplements can help to boost NAD+ levels. You can’t just take a NAD+ supplement because it will not be able to survive the digestion process while its precursors have been shown to be able to and undergo conversion into NAD+.

NR is uniquely bioavailable in the body, supplementation can increase NAD+ levels by 2.7 fold in a single dose. Supplementing with NR can help to increase insulin sensitivity, improve exercise performance, decrease oxidative stress, increase neuroproduction, improve stem cell function, improve mitochondrial function, increase resistance to the negative effects of a high fat diet, improve blood flow, assist in non-alcoholic fatty liver disease, and extend lifespan.