Nicotinamide Riboside Reprograms Aging Stem Cells

 

By Mickey Johnston

A study published in the leading academic journal Science in April 2016 showed that supplementation of aged mice with nicotinamide riboside, a form of vitamin B3, resulted in both increased lifespan and enhanced healthspan.1

Scientists found that nicotinamide riboside has the ability to reprogram dysfunctional stem cells to function as they did in youth.(1)

Although this study was done on mice, it suggests enormous promise for nicotinamide riboside to halt and reverse human aging factors.

Nicotinamide riboside functions to boost cell levels of the energy-factor NAD+.

In this article, we will review the implications of this research for human longevity. We’ll also review the beneficial impact of nicotinamide riboside on obesity, fatty liver disease, and cognitive impairment.

Landmark Study

Landmark Study

An international group of researchers investigated the impact of nicotinamide riboside on life-span and functions related to overall health.1 The results, published in mid-2016, were remarkable.

Aged mice (24 months old) treated with nicotinamide riboside for 6 weeks survived, on average, 5% longer than control mice.(1)

While this may seem to be a fairly modest increase, consider two points.

First, the supplementation began when these mice were already fairly advanced in age.

Second, the average human life expectancy today is about 78.8 years.2 A 5% increase in this figure would add nearly 4 years, a significant increase if those years are healthy and rewarding ones.

Perhaps most importantly, this study suggests that the supplemented animals were healthier overall compared with controls.

Here are the highlights of those findings:(1)

  • Aged mice supplemented with nicotinamide riboside demonstrated increases in maximal running times and distances, and in grip strength.
  • Chemically damaged muscle tissue from supplemented mice was regenerated faster, and regenerated muscle was bulkier than in mice fed the control diet.
  • Supplemented mice showed increased proliferation and development of new brain cells, especially in the memory-intensive hippocampus region of the brain, compared with control animals.

Reprogramming Dysfunctional Stem Cells

With aging, adult stem cell function declines (stem cell senescence), causing a loss in tissue homeostasis and regeneration.(1)

Researchers found that nicotinamide riboside increased strength, endurance, and recovery times in aged mice because it increased the number and function of muscle stem cells, providing the mice greater resources for maintaining strong, healthy muscles.(1)

This study showed that supplementation with nicotinamide riboside led to significant improvements in lifespan and factors influencing health. The fact that these changes occurred in aged mice gives hope to older individuals who are looking for viable ways to live longer, healthier lives.

How it Works

How it Works

The reason why nicotinamide riboside is such a potent promoter of healthspan and lifespan is because once it enters the body, it converts to one of the most essential factors in energy production in cells, nicotinamide adenine dinucleotide(NAD+).

NAD+ has two key functions in the body that help combat aging. First, it enhances cellular energy by boosting the function of mitochondria, the body’s cellular “power plants” that convert the food we eat into energy our bodies can use.3 While age-related mitochondrial dysfunction can result in tissue and organ failure, studies show that restoring mitochondrial function slows aging and extends longevity.1

Second, NAD+ activates enzymes called sirtuins that control gene expression. SIRT enzymes “turn off” certain genes that promote aging, such as those involved in inflammation,4,5 in fat synthesis and storage, and in blood-sugar management.6,7

By boosting the body’s levels of NAD+, nicotinamide riboside helps protect the body against some of the most potent age-accelerating processes that threaten longevity. Three of these disorders include obesity, nonalcoholic fatty liver disease, and cognitive decline.

Let’s look at nicotinamide riboside’s impact on each one:

  • Obesity: A 2012 paper showed that nicotinamide riboside supplementation in both cultured cells and tissues activates sirtuins, which boost fat-burning and prevent some of the metabolic changes induced by obesity.8
  • Nonalcoholic fatty liver disease: NAFLD is the most common chronic liver disorder in industrialized nations and one closely related to our obesity epidemic.9 Nicotinamide riboside was found to prevent—and even reverse—NAFLD in mice on a high-fat, high-sugar diet. This effect was due to its ability to increase sirtuin activity, which resulted in sharp increases in mitochondrial fat burning as well as increases in the energy storage molecule ATP, which all cells require to perform their functions.9
  • Alzheimer’s disease: Mitochondrial dysfunction and poor energy management in brain cells are closely associated with the development of Alzheimer’s disease.10 Nicotinamide riboside helps combat both of these factors. A recent study of a mouse model of Alzheimer’s showed that supplementation with nicotinamide riboside for three months significantly slowed cognitive deterioration.10 As expected, these results appeared to arise from the supplement’s ability to improve energy production in brain cells.

Summary

The concept of radical life extension is steadily moving from science fiction to science reality

The concept of radical life extension is steadily moving from science fiction to science reality.

Nicotinamide riboside shows evidence of enhancing the healthspan as well. This is vital, because added years of low-quality life do not represent, for most people, much of a gain.

This landmark study indicates that supplementing with nicotinamide riboside could help one live longer and healthier. More research is urgently needed to corroborate these remarkable findings.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Zhang H, Ryu D, Wu Y, et al. NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science. 2016;352(6292):1436-43.
  2. Available at: https://www.cdc.gov/nchs/fastats/life-expectancy.htm. Accessed December 21, 2016.
  3. Guarente L. CELL METABOLISM. The resurgence of NAD(+). Science. 2016;352(6292):1396-7.
  4. Kotas ME, Gorecki MC, Gillum MP. Sirtuin-1 is a nutrient-dependent modulator of inflammation. Adipocyte. 2013;2(2):113-8.
  5. Galli M, Van Gool F, Leo O. Sirtuins and inflammation: Friends or foes? Biochem Pharmacol. 2011;81(5):569-76.
  6. Li X, Kazgan N. Mammalian sirtuins and energy metabolism. Int J Biol Sci. 2011;7(5):575-87.
  7. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25(3):138-45.
  8. Canto C, Houtkooper RH, Pirinen E, et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-47.
  9. Gariani K, Menzies KJ, Ryu D, et al. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice. Hepatology. 2016;63(4):1190-204.
  10. Gong B, Pan Y, Vempati P, et al. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-gamma coactivator 1alpha regulated beta-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging. 2013;34(6):1581-8.

Research shows Nicotinamide Riboside may prevent Liver Disease

liverdisease

Nonalcoholic fatty liver disease (NAFLD) is the underlying problem being most liver disease in the US and other western countries due to the prevalence of obesity.

It can result in total liver failure and death. With nearly 37%  of adults in the US now classified as Obese, and projected to be 60% in the next 10 years, the problem is only going to get worse.

Although there are many contributing factors, insulin resistance plays a key role in the deterioration of the livers ability to process the fat.

Mitochondria dysfunction also contributes to inflammation and fibrosis further impacting the liver function.

This study  demonstrates that boosting NAD+ can  protects  against many age and diet related chronic diseases such as chronic liver failure.

The results confirm prior studies on the role NAD+   plays in supporting sirtuinsi to repair cellular damage, and in particular protecting from NAFLD.

The research shows that a diet high in  fat and sugar contributes to NAFLD, and that adding Nicotinamide Riboside to the diet boosts NAD+ levels which improves Mitochondria unfolded protein response (UPRMT) to help prevent and reverse NAFLD.

For the study,  SIRT Knockout Mice were fed a high-fat, high-sucrose diet, or normal chow diet.   1/2 the mice were also fed  500 mg/kg Nicotinamide Riboside pellets for 18 weeks.

From the data, the researchers postulated that boosting NAD+ levels increases sirtuin-mediated UPRmt activation and mitochondrial biogenesis, while also reducing UPRer stress response.

In agreement, they found nicotinamide riboside attenuated the severe mitochondrial dysfunction, typified by reduced mitochondrial content and function, present in fatty livers of mice fed a long-term high-fat high-sucrose diet.

These robust effects of NR on mitochondrial function were reliant on the NAD+-mediated SIRT1 and SIRT3 induction of mitonuclear protein imbalance, triggering the UPRmt.

Similar to previous reports linking the beneficial effects of NMN and NR to the UPRmt activation of UPRmt in livers of these NR-treated animals maintained optimal mitochondrial function despite a chronic FA overload.

Overall the data shows that boosting of depleted liver NAD+ stores in mouse models of NAFLD, by administration of Nicotinamide Riboside supplements, recovers liver NAD+-dependent SIRT1 and SIRT3 signaling to counteract the development of NAFLD.

And that the beneficial effects of NR are largely mediated by the cell-autonomous effect of SIRT1 activation in the liver.

Using the FDA guidelines for converting the dosage tested to humans, the 500 mg/kg results in a daily dosage of around 2,200 mg for a person weight 160 lbs.  This is in the range used for other testing with mice for therapeutic purposes.

Note that this is much higher than the dosage used in recent testing for safety.  It is also nearly 4x the  recommended by most brands, and more than double the amount used in recent testing to measure NR’s ability to raise NAD+ levels.

Chromadex is currently performing tests with humans at various dosage levels to determine optimum and safe dosage levels.