NAD+ AND AGING
Nicotinamide-Adenine-Dinucleotide or NAD+ for short is a coenzyme of vitamin B3 that is vital for every cell of the human body. This molecule is essential for energy synthesis, cellular regeneration, repair of DNA damage, and prevention of aging. It participates in over 500 enzymatic reactions and plays a key role in the regulation of almost all major biological processes.
NAD+ is a key regulator of cellular processes that controls the body's response to stress. Its fluctuations affect mitochondrial function and metabolism, redox reactions (any chemical reaction in which both reduction and oxidation occur), circadian rhythm, immune response, inflammation, DNA repair, and cell division (1). NAD+ levels by age decrease, causing a slowdown in metabolism and increased risk of cardiovascular, endocrine, and mental disorders. That’s why NAD+ is considered a key factor in healthy aging and longevity.
NAD+ was first discovered in 1906 by British biochemists Arthur Harden and William John Young, who studied enzymatic processes involving sugars and scientifically substantiated the existence of this molecule. Only 20 years later, the structure of NAD was described in detail by Hans von Euler-Chelpin, who called it "cozymase" and showed that it consists of two nucleotides. For their discovery, Sir Arthur Harden and Euler-Chelpin were awarded the Nobel Prize in Chemistry in 1930. Throughout the 20th century, this key cell coenzyme will bring many more Nobel Prizes and pose many mysteries to its researchers. Now literally the whole world is following the discoveries in the field of NAD+ since the latest data show that this molecule is directly related to the aging of living organisms.
NAD+ is a coenzyme of vitamin B3 and plays a critical role in many biological processes in the body. Actually, NAD+ is the main regulator of biochemical processes in the cell involved in redox reactions. It takes electrons from some molecules and transfers them to others - in this way the energy that a person receives from food is converted into chemical energy that feeds our body and brain. This coenzyme promotes the production of a strong antioxidant ATP by mitochondria - the main source of energy in the human body, it also supports our nervous system, and participates in metabolic processes.
NAD+ levels decrease significantly with age and chronic inflammation is an important reason for the decline its levels. The inflammation causes an increase in the level of the cellular enzyme CD38, which breaks down NAD+ and is actually its precursor. Increased levels of CD38 reduce NAD levels by age and accelerate aging.
NAD+ increases sirtuins levels as well. Sirtuins are specialized proteins that not only regulate intracellular homeostasis, but also participate in inflammation processes, fat synthesis and storage, blood sugar regulation, and aging (2). In a research study published in Nature, the authors refer to these proteins as “longevity proteins” to emphasize their important role in slowing aging (3). Some aspects of NAD anti aging properties are sirtuin-dependent. The higher the NAD+ levels, the higher the activity of sirtuins (4).
Data analysis show that NAD levels by age are reduced regardless of the quality of life and overall health. By the age of 40, NAD+ levels are reduced by 50%, and by the age of 60, by 80%. Recent studies show that low NAD levels by age accelerate the aging of the body since a connection between a decrease in coenzymes and the occurrence of age-related diseases has been established. With a decrease in the NAD+ levels, which means that less ATP is produced, organs and tissues receive less and less energy, cells are more and more depleted, and die as a result.
Low NAD+ levels by age can cause metabolic slowdown, leading to weight gain and poor blood sugar control, rapid fatigue, and deterioration of blood vessels. This increases the risk of heart disease and diabetes mellitus. Also, a decrease in NAD+ can lead to an age-related decrease in muscle mass (sarcopenia), impairment of mental health, a decrease in visual acuity and hearing. How to Increase NAD+ Levels?
There are several options to increase NAD+ levels in a natural way. Here are the most common of them:
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Regular Exercise
Physical activity is another great way to increase your natural production of NAD+. Exercise boosts your metabolism, so your heart, lungs, muscles, and brain require more energy. During exercise, our bodies use the energy that comes from NAD +. That’s why the body increases its production of NAD+ during physical activity to meet these needs. Basically, exercise forces the muscles in our body to increase the number of mitochondria, which are kind of the "cell powerhouse". As a result, increased production of mitochondria naturally increases NAD+ levels in the body.
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Sauna and Thermal Effects
Whether you decide to shower in the sauna or sunbathe on a warm summer day, body warming is another good way to boost your NAD + levels. When the body temperature rises, the cooling system turns on, which requires energy. The energy used to cool the body increases NAD+ levels.
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Diet
There are certain foods that can increase the levels of NAD in the body. Studies have shown that cow's milk is a good source of nicotinamide riboside, which positively affects the metabolism of NAD. A liter of fresh cow's milk contains approximately 3.9 µmol of NAD +. Additionally, some varieties of fish, such as tuna, salmon, and sardines, are rich sources of NAD+. You should also pay attention to grains as they are a rich source of vitamin B3, which contains NR, the precursor (creator) of NAD. Nicotinamide riboside anti aging properties have been investigated in recent clinical trials showed NR benefits over other NAD+ precursors (5). Avoid excessive alcohol consumption as it tends to interfere with normal metabolic processes and reduce NAD+ levels.
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Supplements
Given the importance of NAD+ for normal cell function and anti-aging, increasing NAD+ levels through nutritional supplements and innovative transdermal patches is becoming increasingly popular. Oral NAD+ supplements in form of sublingual lozenges have high bioavailability, contain relatively high doses of NAD+ coenzyme and effectively increase intracellular NAD + levels when taken long-term. Transdermal patches are a more convenient alternative to sublingual lozenges because they require little or no attention during long-term use, contain a high concentration of NAD+ and provide optimal dosing throughout the day.
NAD + is an essential molecule for the body's energy production and regulation of key cellular processes. Low NAD+ levels by age cause metabolic slowdown, increase risk of heart disease, type 2 diabetes mellitus, and accelerate aging. To increase and maintain NAD+ levels one should regularly exercise, eat healthy food and use NAD+ supplements. NAD+ supplementation provides health benefits due to the restoration of intracellular NAD+ levels and reactivation of sirtuins, as well as other important NAD+ dependent biomolecules (6).
Goody, M. F., & Henry, C. A. (2018). A need for NAD+ in muscle development, homeostasis, and aging. Skeletal Muscle, 8(1), 1-14.
Wątroba, M., Dudek, I., Skoda, M., Stangret, A., Rzodkiewicz, P., & Szukiewicz, D. (2017). Sirtuins, epigenetics and longevity. Ageing research reviews, 40, 11-19.
Imai, S. I., Armstrong, C. M., Kaeberlein, M., & Guarente, L. (2000). Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature, 403(6771), 795-800.
Belenky, P., Bogan, K. L., & Brenner, C. (2007). NAD+ metabolism in health and disease. Trends in biochemical sciences, 32(1), 12-19.
Search of: Nicotinamide riboside - List Results - ClinicalTrials.gov. (2021). U.S. National Library of Medicine. https://clinicaltrials.gov/ct2/results?cond=&term=Nicotinamide+%20riboside&cntry=&state=&city=&dist=
Imai, S. I., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in cell biology, 24(8), 464-471.
