NAD+ is a fundamental component of the human body involved in many cellular processes. But, where does our body produce it in the first place? Scientists have discovered NAD+ derives from the precursors from which it is synthesized. Such NAD+ precursors have been found to play an important role in longevity, which will be the primary focus of this article.
Learn About NAD+ Precursors That Affect the Years of Your Life
What Are NAD+ Precursors?
NAD+ is a critical coenzyme in the human body involved in various functions, including energy metabolism, cell signaling, mitochondrial maintenance, and cell survival dictation. On the other hand, NAD+ precursors are the molecules that serve as the intermediates in NAD+ generation. In other words, they are the molecules from which NAD+ is synthesized. There are five NAD+ precursors as below:
- Tryptophan (Trp)
- Nicotinic acid (NA)
- Nicotinamide (NAM)
- Nicotinamide mononucleotide (NMN)
- Nicotinamide riboside (NR)
NAD+ decreases with age, which results from the reduced synthesis and increased consumption of NAD+ by enzymes. Therefore, it would be optimal if the body could perpetually synthesize NAD+ to maintain sufficient NAD+ content. Rather than control the enzymes that constantly consume NAD+ to achieve NAD+ preservation, pharmaceutical supplementation of NAD+ precursors is more practical, hence easier to achieve.
NAD+ Precursors and Aging
In addition to NAD+ functions as mentioned above, its role in organismal longevity has recently been under investigation. While NAD+ is efficiently preserved through the balance between NAD+ generation and consumption in young and healthy people, it decreases during biological aging and in several age-related diseases, including Alzheimer’s disease. On this account, there is an association between NAD+ depletion and aging, prompting intensive research into NAD+ restoration.
According to a review, restoring NAD+ results in beneficial effects that improve healthspan in aged individuals, one of which is prohibiting cellular senescence, a hallmark of aging. Moreover, NAD+ prolongs lifespan and alleviates several conditions, such as premature aging diseases in preclinical trials. NAD+ also improves systemic and organic dysfunction and extends lifespan in mice. These findings suggest that NAD+ restoration through NAD+ precursors can play a role in targeting aging and age-related diseases.
Although scientists have discovered a total of five NAD+ precursors, not every one of these molecules plays a role in aging and longevity. Instead, only NMN and NR have recently shown potential in slowing down aging and promoting healthy longevity. The same review above records more than 30 clinical trials on NMN and NR and their health benefits, indicating their great possibilities for this particular purpose.
Nicotinamide Mononucleotide (NMN)
According to studies, using NMN to restore and enhance NAD+ has shown plenty of health benefits in mice, including reversing vascular dysfunction, reducing oxidative stress, suppressing age-associated body weight gain, enhancing physical activity, and improving insulin sensitivity. Most importantly, NMN can alleviate age-related phenotypes, which are the significant risk factors that cause susceptibility to age-related diseases.
Additionally, NMN treatment has increased longevity by 117 percent in studies on animal models. Further, supplementing NMN to treat metabolic, neurodegenerative, and premature aging diseases can increase NAD+ levels, leading to improvements in disease pathologies, such as mitochondrial dysfunction, which is another hallmark of aging along with cellular senescence mentioned above.
Nicotinamide Riboside (NR)
According to the same review, NR shows significant potential in healthy longevity. It can prolong lifespan in subjects with neurodegenerative and premature aging diseases. In studies on mouse models with premature aging diseases, NR administration can increase both health and lifespan similarly to NMN. In addition, NR can prevent detrimental effects due to high body fat, suppress body weight gain, and enhance insulin sensitivity and mitochondrial content.
Is Using NAD+ Precursors Safe?
Most NAD+ precursors, including NMN and NR, are safe at the tested doses. Specifically, NMN is well-tolerated at low doses, yet higher doses may need further experiments to conclude safety. In a study involving healthy Japanese men, NMN 500 mg was safe and caused no significant side effects. Likewise, a study has proven that NR in doses up to 1000 mg was well-tolerated in humans.
Given the massive amount of research done on the benefits of NAD+ in treating age-related diseases, NAD+ restoration by using NAD+ precursors has excellent potential in promoting health and longevity.
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