Nicotinamide Mononucleotide (NMN)
The Importance of Boosting NAD+ with NMN
After water, NAD+ is the most abundant molecule in the body and is necessary for life. NAD+ is a coenzyme — a “helper” molecule that enzymes need to function. Enzymes are a specialized type of protein that make chemical reactions much faster. For example, without enzymes some biological reactions would take 2.3 billion years to finish. Thus, life would likely not exist without enzymes.
Importantly, with age, and in cases of chronic diseases like obesity, cardiovascular disease, neurodegenerative disease, and sarcopenia (age-related muscle wasting), NAD+ declines. Thus, restoring NAD+ levels under these circumstances with NAD+ precursors like NMN can potentially mitigate the ill effects of aging and even prevent or reverse chronic diseases. The anti-aging and pro-longevity effects of boosting NAD+ in both animal models and humans is currently supported by a growing body of scientific evidence.
NAD+ Activates Sirtuins
NAD+ fuels a critical class of enzymes called sirtuins. Sirtuins are what some call “guardians of the cell,” as they play an active role in repairing DNA and supporting the health of our mitochondria. Mitochondria are referred to as the powerhouse of the cell because they produce cellular energy called ATP. Unhealthy mitochondria produce less ATP, which leads to cell death. Since excessive DNA damage also leads to cell death, sirtuins promote cell survival by repairing DNA and keeping mitochondria pristine.
As David Sinclair, a Harvard geneticist and NAD+ researcher says we lose NAD+ as we age “and the resulting decline in sirtuin activity, is thought to be a primary reason our bodies develop diseases when we are old but not when we are young.” He believes that increasing NAD+ levels, including with NMN during aging may slow or reverse certain aging processes.
In addition to NMN, polyphenols — longevity-promoting plant-based molecules, exercise and caloric restriction — consuming less calories without malnourishment can also boost NAD+ levels and activate sirtuins. In addition to increasing cell survival and protecting DNA (genomic stability), sirtuins provide a multitude of benefits. Sirtuins protect against diabetes and fatty liver by improving insulin secretion from the pancreas, promoting fat metabolism in the liver, and elevating liver glucose production. Sirtuins also protect against sarcopenia, neurodegenration, and fat (adipose) tissue gain.
NAD+ Functions as a Coenzyme in Mitochondria
NAD+ plays an especially active role in metabolic processes, such as glycolysis, the TCA Cycle (AKA Krebs Cycle or Citric Acid cycle), and the electron transport chain, which occurs in our mitochondria and is how we obtain cellular energy.
In its role as a ligand, NAD+ binds to enzymes and transfers electrons between molecules. Electrons are the atomic basis for cellular energy and by transferring them from one molecule to the next, NAD+ acts through a cellular mechanism similar to recharging a battery. A battery is depleted when electrons are expended to provide energy. Those electrons can’t return to their starting point without a boost. In cells, NAD+ serves as that booster. In this way, NAD+ can decrease or increase enzyme activity, gene expression, and cell signaling.
NAD+ Helps Control DNA Damage
As organisms grow older, they accrue DNA damage due to environmental factors such as radiation, pollution, and imprecise DNA replication. According to the current aging theory, the accumulation of DNA damage is the main cause of aging. Almost all cells contain the ‘molecular machinery’ to repair this damage. This machinery consumes NAD+ and energy molecules. Therefore, excessive DNA damage can drain valuable cellular resources.
One important DNA repair protein, PARP (Poly (ADP-ribose) polymerase), depends on NAD+ to function. Older individuals experience decreased levels of NAD+. The accumulation of DNA damage as a result of the normal aging process leads to increased PARP, which causes decreased NAD+ concentration. This depletion is exacerbated by any further DNA damage in the mitochondria.
Why Should We Care About NAD+
Since the discovery of NAD+ in 1906, the molecule has been on scientists’ radar for its abundance in the body and its crucial role in molecular pathways that keep our body running. In animal studies, raising NAD+ levels in the body have shown promising results in research fields like metabolic and age-related disease and has even shown some anti-aging properties. Age-related illnesses such as diabetes, cardiovascular diseases, neurodegeneration and general decreases in the immune system.
Aging
NAD+ is the fuel that helps sirtuins sustain genome integrity and promote DNA repair. Like a car cannot drive without fuel, sirtuins’ activation requires NAD+. Results from animal studies showed that raising NAD+ level in the body activates sirtuins and increases the lifespans of yeast, worms and mice. Although animal studies showed promising results in anti-aging properties, scientists are still studying how these results can translate to humans.
Metabolic Disorders
NAD+ is one of the keys to maintaining healthy mitochondrial functions and steady energy output. Aging and high-fat diet reduces the level of NAD+ in the body. Studies have shown that taking NAD+ boosters can alleviate diet-associated and age-associated weight gain in mice and improve their exercise capacity, even in aged mice. Other studies even reversed the diabetes effect in female mice, showing new strategies to fight metabolic disorders, such as obesity.
Heart Function
Boosting NAD+ levels protect the heart and improves cardiac functions. High blood pressure can cause an enlarged heart and blocked arteries that lead to strokes. In mice, NAD+ boosters have replenished NAD+ levels in the heart and prevented injuries to the heart caused by a lack of blood flow. Other studies have shown that NAD+ boosters can protect mice from abnormal heart enlargement.
Neurodegeneration
In mice with Alzheimer’s, raising the NAD+ level can decrease protein build up that disrupts cell communication in the brain to increase cognitive function. Boosting NAD+ levels also protect brain cells from dying when there’s insufficient blood flow to the brain. Many studies in animal models present new prospects of helping the brain age healthily, defending against neurodegeneration and improving memory.
Immune System
As adults get older the immune system declines, people get ill more easily, and it becomes harder for people to bounce back from illnesses such as the seasonal flu, or even COVID-19. Recent studies have suggested that NAD+ levels play an important role in regulating inflammation and cell survival during the immune response and aging. The study underscored the therapeutic potential of NAD+ for immune dysfunction.