The relationship between NAD+ and Sirtuins in aging
There has been extensive research to discover molecules that hold an answer to delay aging and increase longevity. In addition, several naturally occurring molecules in our body have also shown their role in aging, and they may be exploited to delay the process.
Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme that regulates enzymes such as sirtuins that consume NAD+. An intimate relationship exists between the NAD+ and sirtuins that control energy utilisation. Furthermore, this lays a foundation in the process of aging and longevity control in a plethora of organisms. It is time for us to explore the relationship between NAD+ and sirtuins in aging.
Let us try and understand more about how the two compounds function as a dynamic couple in the aging and longevity of humans.
NAD: An essential moiety in cellular processes and metabolism
Being discovered a century ago, NAD+, a hard-working molecule, mediates various reactions inside every cell in our body that create energy. These reactions involve the oxidation of nutrients, commonly referred to as the metabolism. Several studies propose that NAD+ is responsible for extending life span and proven ways such as dietary restrictions for increasing health-span.
NAD+ is an essential fuel for our body’s numerous processes, like converting food into energy. It also repairs the damaged DNA, builds cells’ defense power, and maintains our body’s internal clock. This clock is a circadian rhythm with a cycle of physical, mental, and behavioral changes that automatically get repeated every 24 hours.
So, in gist, NAD+ increases stress resistance, boosts our health, and also the lifespan. However, its levels drastically drop as you age. So what happens as you age? With increasing age, the amount of NAD+ in our body naturally falls. Low levels of NAD+ are directly linked to the risk of developing old age diseases like diabetes, loss of vision, Alzheimer’s disease, and many more. Studies indicate that if you are provided with NAD+ at an older age, you will get several health benefits to counter aging-associated pathologies and accelerated aging. The good news is that supplements of NAD+ intermediates may normalize this deficiency. NAD+ also activates certain enzymes in our body that help promote healthy aging. One such example is sirtuins. Let's now understand what these sirtuins do.
Role of Sirtuins
Sirtuins are a family of enzymes in our body that help control age-related diseases and improve lifespan. However, they work in collaboration with NAD+. Several research studies have proved their health-span and lifespan-extending benefits, anti-aging mechanisms of caloric restriction, and intermittent fasting. Sirtuins are the major players in delaying biological aging. The sirtuins activation not only increases metabolism inside the cells but also reduces oxidative stress. Many age-related diseases like diabetes, Alzheimer’s, cancer, and heart diseases are mainly due to oxidative stress in the body. Their actions prevent premature aging, as seen in calorie restriction. Calorie restriction, a form of reducing average daily caloric intake and intermittent fasting, has shown to increase lifespan, delay aging and control some diseases in the older age.
The combined action of all 7 members of the sirtuin family builds our immunity, reduces inflammation, and thus helps reduce the risk of chronic inflammatory diseases like diabetes, Inflammatory bowel disease, cancer, and many more. Hence, the overall effect of sirtuins contributes to anti-aging and controlling diseases at an older age.
Effect of sirtuins on circadian cycle and how it affects NAD+
Circadian rhythms are 24-hour cycles that are part of the body's internal clock. One of the most important and well-known circadian rhythms is the sleep-wake cycle. Sirtuins also regulate our body’s biological clock the way NAD+ does. The simplest example of a disturbed biological clock is jet lag. NAD+ and sirtuins work together to reset it to normal. However, as you age, the enzymes from the sirtuins family deplete, resulting in defects in the circadian cycle that causes premature aging and several age-related degenerative diseases. Reciprocally, the synthesis of NAD+ is also regulated by the circadian cycle. Hence, any change in the cycle results in depletion in the NAD+ levels.
By now, scientists have learned the game of NAD+ and sirtuins. The interesting connection between the pair is clearly understood. Sirtuins depend on NAD+ for their activity. Therefore, the availability of NAD+ is a boost for the action of sirtuins. The intimate interplay between NAD+ and sirtuins makes you physiologically robust and mitigates age-associated functional decline, just like lifespan expansion through calorie restrictions.
Overcoming the depletion of NAD and sirtuins as we age
With increasing age, the NAD+ levels drop. The communication between the cell components gets compromised as NAD+; the mediator is deficient. Thus, the connection between NAD+ and sirtuins at every tissue level breaks down, resulting in a decline in body functions. As a result, the activity of the sirtuins also reduces. This causes the collapse of cells functioning that causes aging.
Research suggests that several natural factors are responsible for the activation of sirtuins. Since then, the hunt for molecules that activate sirtuins is on. One such animal study proves that the effect of sirtuins is similar to a calorie-restricted diet. Members of the sirtuin family get activated by plant polyphenols, flavones, stilbenes, chalcones, and anthocyanidins that protect against harmful effects of a high-calorie diet, delay age-related diseases, and improve exercise endurance. Thus, sirtuins are regarded as the novel approach as therapeutic agents to target diabetes, cancer, inflammatory diseases, and neurodegenerative disorders. It is the basis of the Sirtfood diet!
In addition, the relationship between NAD+ and sirtuins provides a deeper understanding of how energy metabolism affects the process of aging. Since NAD+ is also one such booster of sirtuins, NAD+ boosting molecules and NAD+ supplements can overcome the depletion of NAD+ and sirtuins. Several such supplements are being researched.
Just as the African Proverb says, “If you want to go fast, go alone. If you want to go far, go together,” so is the relationship of NAD+ and sirtuins. Together they pave the path of delayed aging, longevity, and good health.
Aging is an irreversible process, but the intimate couple NAD+ and sirtuins together can modulate and delay aging. Together, they also control several diseases by regulating metabolism, increasing stress resistance, handling the process of transcription, cell survival, and proliferation. It will also improve the quality of life during aging.
About Eugene He
Eugene is the founder of Invity, a clinical naturopath and a nutraceutical formulator. He has spent the past twenty years educating and writing about nutrition, phytotherapy and general wellness. His work has been featured in Forbes, Yahoo, Tatler, CEW, Allure and many other publications around the world.
- Imai, Si., Guarente, L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. npj Aging Mech Dis 2, 16017 (2016).
- Imai, S., & Guarente, L. (2014). NAD+ and sirtuins in aging and disease. Trends in cell biology, 24(8), 464–471.
- Rajman, L., Chwalek, K., & Sinclair, D. A. (2018). Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell metabolism, 27(3), 529–547.
- Guarente, L. (2018). Sirtuins, NAD +, Aging, and Disease. Introductory Review on Sirtuins in Biology, Aging, and Disease, 1–6. doi:10.1016/b978-0-12-813499-3.00001-0
- Bonkowski, M. S., & Sinclair, D. A. (2016). Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nature reviews. Molecular cell biology, 17(11), 679–690.
- Gaur, U., Tu, J., Li, D., Gao, Y., Lian, T., Sun, B., Yang, D., Fan, X., & Yang, M. (2017). Molecular evolutionary patterns of NAD+/Sirtuin aging signaling pathway across taxa. PloS one, 12(8), e0182306. https://doi.org/10.1371/journal.pone.0182306