Monthly Archives: April 2019

The 8 Most Important Things You Need to Know About NMN

Three studies published in 2018 all show that several cardiovascular diseases stemming from vascular aging can be reversed by stimulating the activation of a group of proteins known as sirtuins. These sirtuins are activated by boosting a molecule called NAD+ through another precursor molecule called NMN ((nicotinamide mononucleotide) that is ingested as a supplement.

Let’s review each of the three studies to see how NMN was tested to improve NAD+ and sirtuins, potentially resulting in the repair of damaged blood vessels.

March 2018 Study

A study lead by Dr. David Sinclair’s lab at Harvard Medical School and published in March 2018showed that the vascular aging process can be reversed in mice, setting the stage for radical new therapies to help people age better. This study has unraveled the cascade of interactions between blood vessels and muscles.

Endothelial cells, which line the walls of blood vessels, are essential for the health and growth of the blood vessels. As endothelial cells age, blood vessels get damaged, begin to atrophy and die, blood flow to many parts of the body diminishes, organs and tissues begin to function poorly.

Damaged blood vessels hit muscles especially hard because muscles rely on a robust supply of blood for their function. Blood vessel atrophy can be slowed down with regular exercise, but not eliminated. At some point, even exercise fails to stave off damaged blood vessels and muscle loss.

What was learned in this study was how aged and damaged blood vessels become deaf to the signals from exercise muscle. This actually leads to these muscles shrinking as we get older. We then are less able to exercise and grow new blood vessels.

The two key players in the crosstalk between blood vessels and muscles are a molecule called NAD+ and a protein called SIRT1 (or sirtuin 1). NAD+ boosts SERT1, which in turn enables the conversation between muscles and damaged blood vessels.

In a series of experiments, the Harvard team found that reduced blood flow develops as endothelial cells start to lose a critical protein known as SIRT1. Previous studies have shown that SIRT1 delays aging and extends life in yeast, fruit flies and mice.

SIRT1 loss is, in turn, precipitated by the loss of NAD+, a key regulator of protein interactions and DNA repair that was identified more than a century ago. Previous research by Sinclair and others has shown that NAD+, which also declines with age, boosts the activity of SIRT1.

The problem is that both NAD+ and SIRT1 decline as we age, gradually becoming less capable of performing their role as the interface between the muscles and blood vessels.

In the attempt to increase NAD+ and SIRT1, the researchers gave mice NMN, a chemical compound commonly found in the body and previously shown to boost NAD+ levels, which in turn augments SIRT1.

Here’s what NMN did to the mice:

  • They had better endothelial function;
  • Their blood vessels grew;
  • The blood supply to their muscles improved; and
  • These animals’ capacity for exercise improved dramatically – the old mice treated with NMN had up to 80% greater exercise capacity compared with mice not consuming NMN.

Watch Dr. David Sinclairsummarize his 2018 study in the video below. He ends with this:

“These results, I believe, can help millions of people who have lost their mobility or simply can no longer exercise, either through frailty, disability or old age. This sets the stage for new medicines that will be able to restore blood flow in organs that have lost it either through a heart attack, a stroke or even in patients with dementia.”

Rewinding the clock on aging blood vesselsfrom Harvard Medical Schoolon Vimeo.

According to Harvard Medical School, Dr. Sinclair’s research team’s ultimate goal is to replicate the findings and, eventually, move toward developing small-molecule, NMN-based drugs that mimic the effects of exercise – enhanced blood flow and oxygenation of muscles and other tissues. Such therapies may even help with new vessel growth of organs that suffer tissue-damaging loss of blood supply and oxygen, a common scenario in heart attacks and ischemic strokes. (1)

Sinclair’s second study published in 2018 underscores his commitment to NMN.

September, 2018 Study

In September 2018, Drs. David Sinclair and Alice Kane published the results of a study they headed called, Sirtuins and NAD+in the Development and Treatment of Metabolic and Cardiovascular Diseases.

The purpose of the study was to examine how the family of seven siturins found in mammals protects against a decline in vascular endothelial function, metabolic syndrome, ischemia-reperfusion injury, obesity, cardiomyopathy and dyslipidemia.

Endothelial functionbegins with the health of the endothelium, a thin membrane that lines the inside of the heart and blood vessels. Endothelial cells release substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function and platelet (a colorless substance in the blood) adhesion. (2)

Metabolic Syndromeis a cluster of conditions – increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels – that occur together, increasing your risk of heart disease, stroke and diabetes. (3)

Ischemia-reperfusion injuryis the tissue damage caused when blood supply returns to tissue after a period of ischemiaor lack of oxygen. (4)

Cardiomyopathyrefers to various diseases of the heart muscle that typically cause the heart muscle to become enlarged, thick or rigid. In rare instances, diseased heart muscle tissue is replaced with scar tissue. (5)

Dyslipidemiais an abnormal amount of lipids (e.g. triglycerides, cholesterol and/or fat phospholipids) in the blood. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. (6)

The activation of sirtuins and NAD+ by consuming NMN was shown to improve all of these cardiovascular events, as well as improve insulin sensitivity, and other health benefits in a wide range of age-related cardiovascular and metabolic disease models.

November, 2018 Study

Yet another study published in 2018, in November, showed that the notable decline in capillary density and blood flow that contributes to mortality and morbidity may be reversed by NAD+ boosters, such as NMN (nicotinamide mononucleotide). (7)

Again, as in other such studies, the increased NAD+ levels stimulated by NMN supplementation activated sirtuins. Specifically, this study demonstrated that SIRT1 in endothelial cells is a key mediator of signals by muscle cells (myocytes) that stimulate new blood vessel growth by pre-existing vessels (pro-angiogenic signals).

Treatment of mice with the NAD+ precursor NMN improves blood flow and increases endurance in advanced aged mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise.

Together, these findings have implications for improving blood flow to organs and tissues, increasing performance in aged individuals.

Conclusions

It’s noteworthy that, as with all published studies on NMN, the three summarized here were not done on humans.

Does that make their findings irrelevant to us?

The scientists don’t think so. Genetically and genomically, the human and the mouse are very similar. Almost all of the genes in mice share functions with the genes in humans.(8)

Moreover, the mouse studies testing NMN’s capacity to boost NAD+ and then sirtuins have been so favorable that researchers like Dr. David Sinclair and Dr. Leonard Guarente take NAD+ precursors themselves; in Sinclair’s case, 1 gram of NMN per day. (9, 10)

Even though thousands of people have been consuming NMN safely for years, it’s effectiveness for humans must be tested. To that end, in a small early trial at Brigham and Women’s Hospital, Dr. Sinclair is testing how the NMN molecule works in people, particularly its effect on aging. (11) In 2016, scientists in Japan have also begun a human trial testing NMN, the results of which have yet to be published. (12)

References

  1. Ekaterina Pesheva: Rewinding the Clock
  2. Cedars-Sinai Medical Center: Endothelial Function Testing
  3. Mayo Clinic: Metabolic syndrome
  4. Wikipedia: Reperfusion injury
  5. Heart.org: What Is Cardiomyopathy in Adults?
  6. Wikipedia:Dyslipidemia
  7. M S Bonkowski, A Das, M Schultz, Y Lu, J Mitchell, L Wu, L Guarente, D Sinclair: Impairment of An Endothelial NAD+ – H2S Signaling Network Is a Reversible Cause of Vascular Aging
  8. The Jackson Laboratory: Why are mice considered excellent models for humans?
  9. Brady Hartman: Dr. David Sinclair, Discoverer of Anti-aging NAD Fad, Speaks About Human Trials of NMN
  10.   Joe Rogan Experience #1234: David Sinclair
  11.   Alice Park: This Compound Can Reverse Aging in Mice. Will It Work in People?
  12.   Innovation Toronto: NMN reduces signs of aging: It’s safety is being tested

The Effects of Nicotinamide Mononucleotide (NMN) on Aging and Longevity

Supplementation with Nicotinamide Mononucleotide (NMN) has preventive and therapeutic effects against age-associated functional decline and common ailments of aging. Even though science has improved our understanding of the progressive decline in function our bodies experience because of aging, there is not yet a clear mechanism that can explain why chronic diseases are an inherent part of the aging process. We expect to live longer lives, but our quality of life is affected by age-related diseases.

Maintaining Cellular Energy Levels at Youthful levels

Many of these age-related impairments have common roots at the cellular level and can be traced back to deficits in the production of cellular energy. NMN has an important effect on the production of cellular energy because it is a critical component in the production of NAD+. Levels of NAD+ are of critical importance for keeping mitochondria, the body’s powerhouse, working at peak, youthful levels. Because of its importance as a NAD+ intermediate, active supplementation with NMN increases the concentration of NAD+ in the body, providing a readily available supply of this important nutrient for the amelioration of age-associated diseases and conditions. As we get older, NAD+ levels consistently decline, energy production is less efficient, and the aging process gains momentum, which contributes to the development of many of the “typical” diseases of aging. (1)

When it comes to the production of NAD+, no other nutrient is more important than NMN. In fact, NMN is considered to be the rate-limiting biosynthetic enzyme for the production of NAD+, not only in humans, but in all mammals. Multiple studies have demonstrated that supplementation with NMN promotes the biosynthesis of NAD+ across organs such as the pancreas, liver, muscle, kidneys, eyes, and blood vessels. (2-7)

Countering Age Related Metabolic Decline

The effects if NMN supplementation go beyond just the increased production of NAD+. Studies done in rodents have shown that NMN improves glucose tolerance in aging mice who developed diabetes because of high-sugar diets. These findings suggest similar effects might be possible in older humans who develop diabetes because of a poor diet. (3-8) Further studies have demonstrated the benefits of NMN supplementation for improving sugar metabolism as we age. NMN increases the production of insulin, when insulin-resistance has been caused by a high-fat diet. This is achieved by restoring adequate production of NAD+ and by reducing inflammation and stress caused by free radical damage, countering the effects of age-related chronic inflammation. (3) These studies have also shown that NMN reduces inflammation in fatty tissue, and improves sensitivity to insulin across several different organs. (9) Most importantly, these beneficial effects were found to be more effective in old age.

Keeping Circulation Young

The circulatory system carries blood rich in oxygen, exchanges heat and nutrients, and removes waste from all the organs and systems in the body. The aging process may lead to chronic changes that diminish the density of the blood vessels that compromise this system. This decline in blood flow worsens over time and contributes to the occurrence of chronic disease and premature aging. (10)

One of the direct consequences of this reduction in blood flow is the loss of muscle mass. This progressive loss of muscle mass is a huge contributor to decreased quality of life in old age due to its impact on performance and loss of mobility. NAD+ precursors such as NMN increase the production and maintenance of blood vessels by repairing damaged DNA at the cellular level, optimizing mitochondrial energy production, and promoting glucose tolerance. (7)

Sirtuin deacetylase (SIRT1) is a compound critical for the production and maintenance of new and existing blood vessels. NAD+ precursors such as NMN are an effective way of stimulating SIRT1 activity. (5) Studies done in rodents show that supplementation with NMN has a dramatic effect on the preservation of blood vessels. In one study, NMN was shown to restore the number of blood vessels and increase circulatory density in old mice, effectively reverting circulatory capacity to levels seen in young mice. Remarkably, the mice that received the NMN supplementations demonstrated a 60-80% improvement in muscle endurance. (11)

Preserving a Sharp Mind in Old Age

One of the most exciting findings regarding how NMN can promote the production of NAD+, is that administration of NMN was shown to cause an increase of NAD+ production in the brain. (12, 13) Findings from recent studies suggest that NMN may be of benefit for preserving cognitive function and protecting neuronal health. Studies done with models for Alzheimer’s showed that NMN had significant, beneficial effects on memory and cognition. (14, 15) NMN not only is protective against the decline in cognitive abilities associated with old age, but has found to be of value for preservation of neurons after a stroke. (16, 17)

Extending Cellular Lifespan

Research into the anti-aging properties of NMN shows that the notion of aging being an irreversible process may no longer be an absolute, experiments done in human stem cells have demonstrated that providing an environment rich in NMN extends the lifespan of these cells by delaying age related decline that is a result of continued cell replication. These anti-aging benefits have been related to NMN’s ability to maintain a high production of NAD+ for production of energy in the cell’s mitochondria. (18)

Conclusion

Anti-aging research has shown that supplementation with NMN, a key NAD+ intermediate, is effective at mitigating age-associated metabolic decline and slowing the progression of a multitude of age-related diseases. NMN has beneficial effects on the production of energy at the cellular level, improves tolerance to glucose, reduces inflammation, helps preserve the circulatory system, repairs DNA, and has beneficial effects on the preservation of cognitive function. NMN has also shown potential as a therapeutic agent against Alzheimer’s disease and other neurodegenerative disorders typical of old age. Supplementation with NMN may be of benefit in preserving endurance and mobility. Preserving the functions of these diverse systems across the body promotes health and longevity and significantly improves quality of life as aging progresses.

References:

  1. Canto, C., Menzies, K.J., and Auwerx, J. (2015). NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 22, 31–53.
  2. Guan, Y., Wang, S.R., Huang, X.Z., Xie, Q.H., Xu, Y.Y., Shang, D., and Hao, C.M. (2017). Nicotinamide mononucleotide, an NAD+ precursor, rescues age-associated susceptibility to AKI in a sirtuin 1-dependent manner. J. Am. Soc. Nephrol. 28, 2337–2352.
  3. Yoshino, J., Mills, K.F., Yoon, M.J., and Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14, 528–536.
  4. Peek, C.B., Affinati, A.H., Ramsey, K.M., Kuo, H.Y., Yu, W., Sena, L.A., Ilkayeva, O., Marcheva, B., Kobayashi, Y., Omura, C., et al. (2013). Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342, 1243417.
  5. Gomes, A.P., Price, N.L., Ling, A.J., Moslehi, J.J., Montgomery, M.K., Rajman, L., White, J.P., Teodoro, J.S., Wrann, C.D., Hubbard, B.P., et al. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155, 1624–1638.
  6. Lin, J.B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., et al. (2016). NAMPT-mediated NAD (+) biosynthesis is essential for vision in mice. Cell Rep. 17, 69–85.
  7. de Picciotto, N.E., Gano, L.B., Johnson, L.C., Martens, C.R., Sindler, A.L., Mills, K.F., Imai, S., and Seals, D.R. (2016). Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15, 522–530.
  8. Caton, P.W., Kieswich, J., Yaqoob, M.M., Holness, M.J., and Sugden, M.C. (2011). Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediate impairment of mouse islet function. Diabetologia 54, 3083–3092.
  9. Stromsdorfer, K.L., Yamaguchi, S., Yoon, M.J., Moseley, A.C., Franczyk, M.P., Kelly, S.C., Qi, N., Imai, S., and Yoshino, J. (2016). NAMPT-mediated NAD(+) biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice. Cell Rep. 16, 1851–1860.
  10. Le Couteur, D.G., and Lakatta, E.G. (2010). A vascular theory of aging. J. Gerontol. A Biol. Sci. Med. Sci. 65, 1025–1027
  11. Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Sinclair, D. A. (2018). Impairment of an Endothelial NAD + -H 2 S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 173(1), 74–89.e20. doi:10.1016/j.cell.2018.02.00
  12. Stein, L.R., and Imai, S. (2014). Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 33,1321–1340.
  13. Yoon, M.J., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., and Imai, S. (2015). SIRT1-mediated eNAMPT secretion from adipose tissue regulates hypothalamic NAD(+) and function in mice. Cell Metab. 21, 706–717.
  14. Wang, X., Zhang, Z.F., Zheng, G.H., Wang, A.M., Sun, C.H., Qin, S.P., Zhuang, J., Lu, J., Ma, D.F., and Zheng, Y.L. (2017). The inhibitory effects of purple sweet potato color on hepatic inflammation is associated with restoration of NAD(+) levels and attenuation of NLRP3 inflammasome activation in high-fat-diet-treated mice. Molecules 22, https://doi.or 3390/molecules22081315.
  15. Yao, Z., Yang, W., Gao, Z., and Jia, P. (2017). Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease. Neurosci. Lett. 647, 133–140.
  16. Park, J.H., Long, A., Owens, K., and Kristian, T. (2016). Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically amelioratesbrain damage following global cerebral ischemia. Neurobiol. Dis. 95, 102–110.
  17. Wei, C.C., Kong, Y.Y., Li, G.Q., Guan, Y.F., Wang, P., and Miao, C.Y. (2017a). Nicotinamide mononucleotide attenuates brain injury after intracerebral hemorrhage by activating Nrf2/HO-1 signaling pathway. Sci. Rep. 7, 717
  18. Son MJ, Kwon Y, Son T, Cho YS. Restoration of Mitochondrial NAD+ Levels Delays Stem Cell Senescence and Facilitates Reprogramming of Aged Somatic Cells. Stem Cells. 2016 Dec; 34(12):2840-2851. doi: 10.1002/stem.2460. Epub 2016 Jul 22

NAD+, The Sirtuin Activator That Governs Aging

In your body, NMN is converted into a related compound called nicotinamide adenine dinucleotide (NAD), which is found in every cell of living organisms and is essential for life.

NAD+ is crucial in fueling the seven different genes in our body that govern aging. These genes are called sirutins and are referred to as SIRT1-7. NAD+ is the sirtuin activator.

The sirtuins are a family of proteins involved in regulating cellular processes including the aging and death of cells and their resistance to stress. Unfortunately, as we age and our NAD+ levels decline, so do our sirutins.

Sirtuins are indispensable for DNA repair, controlling inflammation and antioxidative defense which makes them good anti-senescence/anti-aging targets.

The vital importance of NMN in activating all of the seven sirtuins is a key explanation of the wide-ranging activity of this supplement.

The sirtuins do not simply increase the numbers of mitochondria within the cell; they stimulate the death and destruction of damaged mitochondria and improve intercellular communication. They almost seem to act as a kind of team of proteins, restoring cellular functions to a much higher level of youthful effectiveness.

Calorie restriction (CR) is so far the only effective way to extend lifespan without genetic or pharmacological intervention. The effects of calorie restriction (besides lifespan extension) are manifested by physiological and behavioral changes, such as reduced body fat, decreased level of growth factors, glucose and triglycerides.

The level of almost all sirtuins, except SIRT4, increases as an effect of calorie restriction Therefore, it’s believed that sirtuins help mediate (bring about) beneficial effects elicited by such a diet.

Let’s examine what each of the seven sirutins do to assist in health and longevity, as described in a study by Dr. Grabowska et al entitled, “Sirtuins, a promising target in slowing down the aging process.”(1)

Sirtuin 1 Repairs DNA and Arteries

SIRT1 is the best studied in the sirtuins family of seven.

Scientists think that the declining NAD+ availability as we age decreases SIRT1 in the liver, while simultaneously increasing DNA damage. Age-dependent decrease in the level of SIRT1 is seen also in the arteries, suggesting its involvement in the aging of the cardiovascular system.

As the level of SIRT1 diminishes, cells become more prone to apoptosis (a form of programmed cell death), researchers believe that declining SIRT1 is one of the mechanisms responsible for sustaining the balance between DNA repair, apoptosis and senescence. (Senescent cells occur when normal cells cease to divide, becoming zombie-like, neither alive or dead, but disrupting normal, healthy signaling between normal cells.)

SIRT1 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Cell survival, longevity, physical activity/increase in CR Cellular senescence, oxidative stress, inflammation, neurodegeneration, cardiovascular diseases, adiposity, insulin resistance, liver steatosis

Sirtuin 2 Can Reduce Body Fat and Oxidative Stress

SIRT2 has been implicated in regulating adipose (fat) tissue development and function. There is less SIRT2 in the fat tissue of obese people and more of it in the white fat tissue and kidneys of mice subjected to calorie restriction. The implication here is that SIRT2 expression is involved in reducing body fat.

The other prominent role SIRT2 has is that it can serve as a cellular senescence marker, given that it’s prominent in senescent (zombie) cells, but not in cells that entered apoptosis (dead cells). However, scientists don’t believe that SIRT2 is a factor in causing senescence, but may be an effect of the changes occurring in cells during senescence.

SIRT2 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Longevity/increase in CR Oxidative stress, neurodegeneration (the progressive loss of structure or function of neurons, including death of neurons)

Sirtuin 3 is Thought to Influence Longevity

SIRT3 is the only sirtuin that current evidence indicates can influence longevity in humans.

A certain polymorphism (a genetic variation) in the SIRT3 gene can be found more often in long-lived people. People with less of it are less likely to survive to an old age.

Mice lacking SIRT3 are characterized by decreased oxygen consumption and a simultaneous increase in the production of reactive oxygen species (ROS, commonly referred to as “free radicals”), as well as higher oxidative stress in muscle.

SIRT3 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Longevity, metabolic health, glucose homeostasis/increase in CR Oxidative stress, neurodegeneration, cardiac hypertrophy (the abnormal enlargement, or thickening, of the heart muscle), adiposity (being severely overweight or obese), liver steatosis (fatty liver disease)

Sirtuin 4 Can Repress Tumors and Help with Autophagy

SIRT4 may act as an oncogene (a gene that can transform a cell into a tumor cell) and tumor suppressor gene, which may be dependent on the affected tissue types and specific tumor environment.

SIRT4 shows enhanced potential as an antitumor therapeutic when used with glucose metabolism inhibitors. More research is expected investigating the use of SIRT4 in combination with chemotherapy drugs, on the glucose metabolism and its effects on autophagy (the condition whereby the cells start to recycle damaged and garbage parts (defects) into basic elements thereby allowing the cells to remodel themselves).(2)

SIRT4 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Currently Unknown Fatty acid oxidation

Sirtuin 5 Helps Reduce Fatty Acids in the Liver and Oxidative Stress

SIRT5 can help eliminate of oxidative stress-promoting ammonium, as well as mitigate a buildup of fatty acids in the liver.

SIRT5 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Increase in CR Oxidative stress, fatty acid oxidation

Sirtuin 6 Regulates Blood Sugar and Decreases Insulin Resistance

The first evidence that sirtuins can be involved in regulation of mammalian aging came from mice lacking SIRT6. It appears that among sirtuins, SIRT6 depletion exhibits the most severe phenotype (observable physical characteristics), as it seems to be indispensable for reaching a normal lifespan.

Three weeks after birth such mice exhibit symptoms of degeneration and premature aging, such as a sudden decrease in subcutaneous fat, lordokyphosis (swayback spine), colitis (inflammatory bowel disease), severe lymphopenia (too few white blood cells), and osteopenia (thinning bones), which all together result in death in about the fourth week of life.

SIRT6 Aging and Age-related Diseases
Increase or Involvement in CR Decrease
Longevity, glucose homeostasis/increase in CR Cardiac hypertrophy, adiposity, liver steatosis, inflammation, insulin resistance

Sirtuin 7 Benefits the Heart

SIRT7 has been shown to have beneficial functions in the heart. SIRT7-deficient mice develop heart hypertrophy (enlarging) and inflammatory cardio-myopathy. SIRT7 appears to regulate heart cell death and damage and has been shown to block stress-induced cardiac hypertrophy by impinging upon ROS (free radical) generation.(3)

References

  1. Wioleta Grabowska, et al: Sirtuins, a promising target in slowing down the aging process.
  2. Guoyu Huang, et al: Sirtuin-4 (SIRT4), a therapeutic target with oncogenic and tumor-suppressive activity in cancer.
  3. Thaddeus T. Schug et al: Surprising sirtuin crosstalk in the heart.

Fix Damaged DNA with NMN

Everybody ages, but no one knows exactly why. What we do know is that increased fatigue, weakened bones and ill health walk in lockstep with aging, as does chronic disease.

Age is the number one risk factor for many diseases, including Alzheimer’s, cancer, cataracts, and macular degeneration. Researchers are making progress in understanding and treating each of these ailments, and in their understanding of the aging process itself.

DNA damage is a big part of the story. And now we know that NMN might help fix damaged DNA.

In 2013, a group of Spanish scientists led by Dr. Carlos Lopez-Otin took a crack at identifying and explaining what they referred to as the “Hallmarks of Aging.” They clearly showed that aging is the outcome of diverse and complex changes in normal biological functions, from dysfunction of proteins and altered communication – both within cells and among distant tissues in the body – to the accumulation of DNA damage.

In 2017, research led by scientists at Harvard Medical School revealed a critical step in a molecular chain of events that allows cells to fix damaged DNA. This occurred by taking a vitamin supplement called NMN that activated a DNA-repair molecule called NAD+ .

Before I review the Harvard study and what its conclusions might mean to your health, let’s examine how DNA damage ages us.

DNA Gets Damaged As We Age

As we age, damage accumulates, including mutations and impairments in DNA repair processes. At the cellular level, decreases in the regenerative abilities of stem cells, impairments in mitochondrial function, and a tendency for proteins to misfold can all contribute to aging.

dna_with_nmn

Credit: DNA Repairs

In the case of DNA, as it replicates, the cellular machinery involved in the process makes mistakes, leading to changes in the DNA sequence. Mutagens such as reactive oxygen species (ROS or free radicals) or UV radiation can also damage DNA. Most of the time, DNA repair mechanisms fix the damage, but errors slip through and accumulate as we age. Aging has also been linked to the deterioration of DNA repair machinery, allowing permanent errors to become more common in older people.

Among many here are three ways DNA damage affects us:

(1) When DNA has become too damaged, cells kill themselves or enter a nonreplicating state, which is called senescence. Though largely dormant, senescent cells may speed the aging process by secreting inflammatory cytokines thought to contribute to atherosclerosis and other aging-related diseases.

(2) DNA scaffolding proteins that typically help stabilize the genome (our genetic material) show changes with age, contributing to impaired cell division, increased senescence, and other aging-related processes.

(3) Telomeres may be especially prone to DNA damage and lose their ability to protect the body from cancer and protect chromosomes from fusing with one another.

Obviously, helping the body repair its DNA damage is a big step to aging more slowly and extending healthspan, if not lifespan. That’s why the findings of the Harvard study are so important.


Credit: Medicalxpress.com

Harvard Shows NMN Boosts NAD+ and Protects DNA

Published March 24, 2017 in Science, the Harvard studyoffers important insights into how and why the body’s ability to fix damaged DNA dwindles over time. It also shows that the signaling molecule NAD+ is a key regulator of protein-to-protein interactions in DNA repair. Experiments conducted on mice show that treatment with the NAD+ precursor NMN mitigates age-related DNA damage and wards off DNA damage from radiation exposure.

If affirmed in further animal studies and in humans, the findings can help pave the way to therapies that prevent DNA damage associated with aging. In addition, they may help with cancer treatments that involve radiation exposure and some types of chemotherapy, which along with killing tumors, can cause considerable DNA damage in healthy cells.

Dr. David Sinclair, senior author of the study said:

“Our results unveil a key mechanism in cellular degeneration and aging, but beyond that they point to a therapeutic avenue to halt and reverse age-related and radiation-induced DNA damage.”(1)

Dr. Sinclair is a professor in the Department of Genetics at Harvard Medical School, co-director of the Paul F. Glenn Center for the Biology of Aging, and professor at the University of New South Wales School of Medicine in Sydney.

See what he says about the Harvard Study:


Interestingly, Dr. Sinclair and his family consume NMN daily. Before he started consuming NMN, the then 47-year-old Professor Sinclair had his blood tested and was told his body had a biological age of 58. After taking a 500 mg NMN pill every morning for three months, he was tested again and his biological age was 32. (2) Now, as Dr. Sinclair told Joe Rogan in an interview, he and his family have increased their dose from 500 mg to one gram of NMN per day. (3)

Dr. Sinclair obviously believes that the benefits conferred to the mice he studied that consumed NMN will also occur in people. That’s because NMN stimulated NAD+ which in turn boosts the activity of SIRT1.

The NAD+/NMN Chain Reaction

At the outset, the Harvard researchers knew that NAD+ is needed to boost the activity of the SIRT1 protein, which delays aging and extends life in yeast, flies, and mice. The problem is that NAD+ declines steadily in all animals as we age, including us. Given that both SIRT1 and PARP1 (a protein known to control DNA repair) consume NAD+ in order to do their work, less NAD+ means fewer health benefits conferred by SIRT1 and PARP1.

A sirtuin is a type of protein involved in regulating cellular processes including the aging and death of cells and their resistance to stress. SIRT1 refers to the first of seven sirtuins that are in mammals. PARP1 is one of a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.

SIRT1 and PARP1 are big players in maintaining a mammal’s vitality, but as mentioned, both of these proteins require NAD+ to function. To increase NAD+ levels, the researchers treated young and old mice with the NAD+ precursor NMN, which makes up half of an NAD+ molecule. NAD+ is too large to cross the cell membrane, but NMN can slip across it easily. Once inside the cell, NMN binds to another NMN molecule to form NAD+.

As expected, old mice had lower levels of NAD+ in their livers, lower levels of PARP1. After receiving NMN with their drinking water for a week, however, old mice showed marked differences both in NAD+ levels and PARP1 activity. NAD levels in the livers of old mice shot up to levels similar to those seen in younger mice. The cells of mice treated with NMN also showed increased PARP1 activity. Overall, the mice showed a decline in molecular markers that signal DNA damage.

NMN Lowers Damage Caused By Radiation

In a final step, the Harvard scientists exposed mice to DNA-damaging radiation. Cells of animals pre-treated with NMN showed lower levels of DNA damage.Such mice also didn’t exhibit the typical radiation-induced aberrations in blood counts, such as altered white cell counts and changes in lymphocyte and hemoglobin levels. The protective effect was seen even in mice treated with NMN after radiation exposure.

Taken together, the results shed light on the mechanism behind cellular demise induced by DNA damage. They also suggest that restoring NAD levels by NMN treatment should be explored further as a possible therapy to avert the unwanted side effects of environmental radiation, as well as radiation exposure from cancer treatments.

References

  1. Harrison Wein, Ph.D.: Researchers find clue to repair of aging DNA
  2. George Tait Edwards: How To Live A Healthy Long Life
  3. Joe Rogan Experience #1234 – David Sinclair: https://www.youtube.com/watch?v=HOTS0HS7aq4

Research Proves You Can Boost NAD+ With Nicotinamide Mononucleotide (NMN)

In 1841 the average girl born in the United Kingdom was not expected to see her 43rd birthday; whereas a girl born there in 2011 was expected to reach age 83, nearly twice as long. These life expectancy numbers are similar in all industrialized countries today. (1)

A doubling in life expectancy in less than 175 years is not due to an amazing increase in lifespan, but in life expectancy. Lifespan has been remarkably steady over the last 2,000 years; it’s life expectancy that has increased so rapidly. The reason life expectancy has doubled stems from the dramatic improvements in healthcare, which has produced a remarkable decline in infant mortality and an improvement in medicine, such as vaccines. (2)

In the modern era, you have an excellent chance of reaching your 60s, 70s and beyond. At the same time, you also have an excellent chance of getting one or more chronic diseases associated with old age, because aging is a major risk factor for disease.

As we grow older, the chances of contracting virtually every chronic disease increase quickly. High cholesterol tends to increase with age – it’s a risk factor for heart attack and stroke. Blood sugar tends to increase with age – it’s a risk factor for type 2 diabetes, also instigated by body fat, which positively correlates with age. Rather than increase as we get older, our muscles wither, a condition known as sarcopenia.

Arguably, aging is the most dominant cause of chronic disease, and yet it’s not being managed. Doctors don’t sit on their hands until you have a heart attack or a stroke – they notice that you have high cholesterol and manage that cholesterol. Likewise, they don’t wait until you have kidney damage caused by diabetes (diabetic nephropathy) – they manage the hyperglycemia. But no one monitors the aging process directly, nor advocates for preventative protocols that could slow down how fast we age.

What we need to do is manage the rate of aging to be able to prevent disease and maintain our physiological and cognitive functionality longer. One way to do that is to activate the cellular signaling pathwaysthat are involved in promoting the only proven method to enhance longevity and healthspan – calorie restriction.

As you’ll soon see, Nicotinamide Mononucleotide (NMN) is such an activator. But first let’s get some understanding about how it works by mimicking the life-sustaining benefits of caloric restriction.

Reduce Calories = Increase Life Span

Studies done on the dietary regimen known as Calorie Restriction (CR) provide irrefutable evidence of the importance of metabolism in the aging process.(3)

CR has been studied extensively in yeast, worms, mice, monkeys and even humans. In a laboratory you can control the caloric consumption of animals during their lifetime, but humans are too long lived and none would appreciate living their life in a lab. Left unaided by scientists, the long term adherence to a CR dietary regimen for a human is extremely difficult for most to maintain, but some people do.

Today in America, only 22 people per 100,000 live to 100. In the UK that number is also 22. Worldwide, a dismal six. Compare those numbers to Japan, the country that currently has the greatest number of known centenarians of any nation with 67,824 according to their 2017 census, or 35 per 100,000 people. (4)

Why are the Japanese typically the longest lived humans? Fewer calories.

The people of Japan, particular those from Okinawa, eat fewer calories as in proportion to their basal metabolic rate (the rate at which the body uses energy while at rest to keep vital functions going, such as breathing and keeping warm.) Another way of looking at it is that Okinawans thrive on a long-term energy deficit. This isn’t because they lack enough food, but by cultural habit, known as hara hachi bu – “to eat until you are 80 percent full.” (5)

The good news is that you might be able to improve your healthspan, and possibly lifespan, without reducing your calories by 20%, but by activating the same cellular pathways that caloric restriction does. The solution to experiencing the benefits of long-term CR would be to identify and use compounds which act as “CR mimetics” (6).

Over the past 20 years, scientists have made great strides in understanding the key cellular components involved in mediating many of the metabolic changes that contribute to the aging process. They have discovered how certain compounds are capable of inducing similar cellular changes that are normally seen during CR.

NAD+ Flips the Switch

In their investigation about how CR can improve longevity, scientists discovered a “molecular switch” that is flipped in response to a nutritional deficit. It’s been found in a family of protein molecules known as sirtuins. Mammals have seven sirtuins, and collectively they are among the important modifiers for lifespan.

Sirtuins are responsible for critical biological functions like DNA expression, cellular health and various aspects of aging. However, sirtuins can only function in the presence of NAD+ (nicotinamide adenine dinucleotide), a coenzyme found in all living cells. (7)

NAD+ is a major metabolic signaling molecule. They are plentiful when we’re young, but decline precipitously as we age. At the age of 50, your NAD+ levels are at about half the level as in your youth. By 80 years of age, NAD+ levels drop to only 1 to 10% of your youthful levels. (7)

One way CR slows down the aging process is by reversing the age-related decline of bioavailable NAD+. This key metabolite plays a crucial role in regulating the activity of many important signaling molecules involved in age-related diseases.

So, given that NAD+ is essential to longevity, but declines as we age, how do you boost it?

The answer is that you must activate its production indirectly. Feeding or administering NAD+ directly into the body is impractical, because the NAD+ molecule cannot readily cross cell membranesto enter cells, and therefore would be unavailable to positively affect metabolism. Instead, precursor molecules to NAD+ – such as NMN – must be used to increase bioavailable levels of NAD+.

Although it’s true that niacin is one such metabolic precursor of NAD+, niacin is separated by many metabolic steps upstream of the final production of cellular NAD+, and thus has a limited impact on the magnitude of NAD+ bioavailability. (8)

Boost NAD+ With Nicotinamide Mononucleotide

In a study published in 2013, Ana P. Gomes, PhD. and her collaborators showed that by administering the NAD+ precursor NMN (Nicotinamide Mononucleotide) in normal drinking water to older mice, NAD+ levels were restored to those normally associated with younger healthy animals. Old mice fed Nicotinamide Mononucleotide for just one week experienced a restoration in muscle mitochondrial function to levels seen in younger mice.

Mitochondria are cellular organelles that function as power plants within a cell. In the same way that a local power plant produces electricity for an entire city, mitochondria are responsible for the production of energy derived from the breakdown of carbohydrates and fatty acids.

Mitochondria oxidize or “burn” carbohydrates, amino acids and fatty acids for energy, yielding ATP. ATP is the cellular form of energy utilized by cellular processes all throughout the body, providing the energy to pump your heart, power neurons in your brain, contract muscles in your limbs, exchange gases in your lungs, extract nutrients from food and regulate body temperature, to name just a few.

In order to provide the massive amounts of ATP needed for movement and exercise, your muscles contain the highest mitochondrial content of any tissue in your body, which is why the finding that NMN restores youthful mitochondrial function in muscle was so important.

But, as the TV commercials say, “That’s not all.”

A2016 studyconducted by Kathryn F. Mills, PhD and 11 of her associates concludes that:

  • NMN is well-tolerated without any obvious harmful effects.
  • NMN suppresses age-associated body weight gain and enhances energy metabolism.
  • NMN improves insulin sensitivity, eye function, and other features with no toxicity.
  • NMN prevents age-associated gene expression changes in a tissue-specific manner.
  • NMN is an effective anti-aging intervention that could be translated to humans.

Nicotinamide Mononucleotide Increases NMN in Blood and NAD+ in Tissues

In the 2016 study, researchers confirmed that NMN entered the bloodstream within 2.5 minutes of oral consumption and increases in NAD+ levels were observed in the liver, skeletal muscle, and cortex of the brain. In addition, they found that the NMN synthesized NAD+ in tissues of the liver and soleus muscle.

These results suggest that orally administered NMN is quickly absorbed, efficiently transported into blood circulation, and immediately converted to NAD+ in major metabolic tissues.

Nicotinamide Mononucleotide Suppressed Age-Associated Body Weight Gain

The average numbers of percent body weight reduction in NMN-fed mice was dose-dependent, and was between 4% and 9%  less, depending on the amount of NMN ingested, than the control group that was not fed NMN. At 12 months, the higher dose NMN group had a decreased fat mass and an increased lean mass compared to controls – meaning that they were both less fat and more muscular.

Nicotinamide Mononucleotide Enhanced Energy Metabolism and Higher Physical Activity

The researchers measured oxygen consumption, energy expenditure, and respiratory quotient for the NMN-fed mice and control group, and found that as compared to the control, the NMN-fed mice experienced:

  • Significantly increased oxygen consumption.
  • Increased energy expenditure.
  • Significantly decreased respiratory quotient, suggesting that NMN-fed mice switched their main energy source from glucose to fatty acids.

Taken together, these results strongly suggest that NMN has significant preventive effects against age-associated impairment in energy metabolism.

Nicotinamide Mononucleotide Improved Insulin Sensitivity and Blood Lipid Profile

NMN-fed mice showed significantly improved insulin sensitivity compared to the control group consisting of body weight-matched individuals. Consistent with this improved insulin sensitivity, triglyceride levels (body fat stores) – a surrogate of insulin resistance – were lower in NMN-fed mice.

As we age, typically insulin sensitivity declines, fasting and average blood glucose levels increases and we gain weight; however the results of this mouse study suggest that long-term NMN consumption can ameliorate age-associated decline in insulin sensitivity, independent of its effect on body weight.

Moreover, the NMN-fed mice experienced less age-associated increases in adipose tissue (body fat) inflammation, a hallmark of obesity and insulin resistance.

Long-Term Nicotinamide Mononucleotide Consumption Significantly Improves Eye Function and Bone Density

NMN prevented the decline in rod cell function in aged NMN-fed mice. Rod cells are photoreceptor cells in the retina of the eye that can function in less intense light than the other type of visual photoreceptor, called cone cells. In addition to these effects of NMN on eye function, the researchers detected small but significant increases in bone density in the NMN-fed mice.

In conclusion, the 2016 Kathryn F. Mills NMN study, asreported in Cell Metabolism, provides:

“… compelling support to an effective anti-aging intervention using NMN, a key NAD+ precursor… it will be of great interest to translate our study from mice to humans and examine whether this endogenous compound, NMN, is also an effective intervention that prevents age-associated physiological decline in humans.”

Of Mice and (Wo)Men

To date, no studies on the ability of NMN to increase NAD+ levels in humans have been published. That’s not to say that such a study hasn’t actually been done.

In 2016, Naturepublished a report: The first human clinical study for NMN has started in Japan, which said:

  • An international collaborative team between Keio University School of Medicine in Tokyo and Washington University School of Medicine in St Louis has started the Phase I human clinical study for NMN to assess the safety and the bioavailability of NMN in humans.
  • NAD precursors and sirtuin activators are attracting significant attention owing to the vast amount of data accumulated in the last 16 years since the discovery of the NAD+ and sirtuin interaction. Although NAD+ itself is difficult to administer directly to humans, its precursors – NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) – are promising natural compounds with which to augment NAD levels in the cells and the body.
  • This phase I study is not planned for a pharmaceutical development, but for a nutraceutical (vitamin) development.

According to a BusinessWirereport, “there are no plans for public disclosure of the clinical research results”; however, based on the results of these clinical studies, the intention is “to create products based on the newly discovered effects of NMN.”

Moreover, Shinkowa Pharmaceutical Co., Ltd., which funded the human NMN trial will establish an NMN manufacturing facility, continue with human clinical trials and “seek business tie-ups with companies that are actively looking to invest in the NMN business and the field of productive aging.”

Although we don’t know yet the specific outcome of the human trial begun in 2016, it seems apparent from Shinkowa’s actions that they were favorable.

References

  1. Office for National Statistics: How has life expectancy changed over time?
  2. Benjamin Radford: Human Lifespans Nearly Constant for 2,000 Years
  3. Richard Conniff: The Hunger Gains: Extreme Calorie-Restriction Diet Shows Anti-Aging Results
  4. Wikipedia: Centenarian
  5. Jeremy Chan: Longevity In A Bottle
  6. NCBI – Pubmed.gov: Calorie restriction mimetics: can you have your cake and eat it, too?
  7. Laboratory of Molecular Bases of Aging, Department of Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Pasteur Str. 3, 02-093 Warsaw, Poland Wioleta Grabowska, Email: lp.vog.ikcnen@akswobarg.w. : Sirtuins, a promising target in slowing down the ageing process
  8. John M.Denu: Vitamins and Aging: Pathways to NAD+ Synthesis

Why you need to boost NAD+

By age 50, people have about half as much NAD+ in their bodies as they did at age 20. Scientists have linked low levels of NAD+ with several chronic diseases, such as multiple sclerosis, Alzheimer’s and cardiovascular disease.

NAD+ is short for “nicotinamide adenine dinucleotide,” and you can’t live without it. This coenzyme is required for the fundamental biological processes that make your life possible.

A coenzyme is a compound that’s necessary for an enzyme to do its job as a catalyst to bring about a biochemical reaction. NAD+ is such a compound. It’s found in every cell in your body and is needed to regulate how quickly your cells age.

Found in virtually all living cells, NAD+ is essential to sustaining life.(1)

A fascinating aspect of NAD+ is its dual role in protecting against factors that age us. This includes mitigating chemical stress, inflammation, DNA damage, and failing mitochondria.

At the same time, NAD+ promotes longevity by facilitating DNA repair and providing cellular benefits associated with caloric restriction and exercise.(2)

So, why don’t we just consume the NAD+ molecule?

Because NAD+ cannot pass through the plasma membrane. It needs a precursor that can boost NAD+ once entering the cell. NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) are the two most common and studied precursors. Of these, the sublingual form of NMN, such as Prohealth’s NMN Pro, is preferable given its enhanced bioavailability.

NAD+ is involved in a multitude of cellular repair processes in our bodies, mainly by activating sirtuins, a family of proteins responsible for a wide range of cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and mitochondrial biogenesis.

As we age, the decline in NAD+ levels causes these critical cellular processes to become less effective, resulting in the cascade of multiple biochemical and physiological effects we call aging.

In 2016, multiple trials of NMN on mice showed that this compound reanimated brain, skin, and muscle stem cells. The treated mice became rejuvenated – with a higher ability to repair their DNA and a slightly increased lifespan.(3)

Your Body Needs NAD+ For Two Fundamental Reasons

NAD+ has two basic roles in your body:

  1. As a vital player in metabolism. NAD+ helps transfer energy from fatty acids and glucose to the mitochondria (our cells’ “power plants”), which converts them to cellular energy; and
  2. As a helper molecule for proteins that regulate other crucial biological activity.

These processes are incredibly important because they are responsible for regulating oxidative stress and circadian rhythms while maintaining the health of DNA and keeping you healthier, longer.

The problem is that NAD+ levels quickly decline as we age. By age 50 a typical person may have only half the NAD+they did in youth. By age 80, NAD+levels drop to only 1% to 10% expressed in youth.(4)

The Science is Conclusive – Boosting NAD+ will Boost Your Health

A plethora of scientific studies have recently focused on NAD+ due to its central role in many essential biological functions, with research in animals tying NAD+ to exceptional benefits, including for us humans.

In particular, researchers have been researching how NAD+ relates to overall health and age-related diseases. For example, consider three animal studies and one – which is rare – human study:

  • A 2016 study found that mice and worms with degenerative muscles had improved muscle function when supplemented with NAD+ precursors.(5)
  • A 2017 study showed that mice supplemented with an NAD+ precursor experienced an increase in DNA damage repair, with tissue in two-year-old mice given the NAD+ precursor looking identical to tissue in three-month-old mice.(6)
  • A 2018 study found that mice with NAD+ precursor supplementation had improved cognitive function, pointing to signs of therapeutic potential for Alzheimer’s disease.(7)
  • Finally, we have a human study that showed convincingly that NAD+ can be increased by precursors, in this case nicotinamide riboside and pterostilbene, which along with resveratrol, is a potent polyphenol that can raise suritins, particularly SIRT2.(8)

These are only some of the recent findings, and they’re sufficiently inspiring for scientists to continue their NAD+ research, including on humans. The reason is simple – increasing NAD+ levels may be a sure-fire way to improve healthy aging.

References

  1. David A. Sinclair: Can NMN Increase Longevity?
  2. Science Daily: Natural compound reduces signs of aging in healthy mice.
  3. Brady Hartman: Can These Revolutionary Technologies Beat Aging In Our Lifetime?
  4. Stephen Harrington, Anti-aging Effects of NAD+
  5. Dongryeol Ryu, et al: NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.
  6. Jun Li, et al: A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.
  7. Hou Y, et al: NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency.
  8. Ryan W. Dellinger, et al: Aging and Mechanism of Disease.

What we believe about Longevity

We believe in order to live a long and healthy life, you must build the right lifestyle habits. And we believe that science-backed supplementation is an important part of that longevity lifestyle.

Science tells us that aging occurs when our body’s repair mechanisms don’t keep up with the damage that accumulates over time. You don’t need to be a scientist to know that this is true. And as you’ve also undoubtedly noticed, some of us age more slowly, live longer and have more vitality than others.

We know from the Blue Zone studies conducted by longevity expert and National Geographic Explorer Dan Buettner that the longest lived, healthiest people in the world (living in the “Blue Zones”) share a specific type of lifestyle built on a plant-dominant diet, strong interpersonal bonds and a sense of purpose. (1)

These life-enhancing qualities exhibited in the Blue Zone can be adopted by us, and magnified by supplementation, as you’ll see in some examples I’ll share below.

We Believe NMN Boosts NAD+ to Youthful Levels

One of the most exciting examples of a supplement that can magnify the benefits of your positive lifestyle habits and virtually turn back the clock on aging is NMN (Nicotinamide Mononucleotide).

NMN acts as a precursor to boost the body’s NAD+ levels. Why is that important? Because NAD+ (nicotinamide adenine dinucleotide), a coenzyme found in all living cells, is essential for the fundamental biological processes that make life possible.

Unfortunately, NAD+ levels decline as we get older. By the age of 50, our NAD+ levels have already dropped by 50% and will continue a steady decline throughout the rest of our lives. Fortunately, though, that’s not the end of the story.

Thanks to the research of Dr. David Sinclair, a Professor in the Department of Genetics at Harvard Medical School and Co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging, we now know that NAD+ can be boosted to youthful levels by administering its precursor – NMN.

Dr. Sinclair is best known for his work on understanding why we age and how to slow its effects. In fact, his longevity research is so highly respected that in 2014, TIME magazine listed him as one of the “100 most influential people in the world.”

So what does one of the world’s most knowledgeable researchers in the science of aging do? He takes NMN – and he gives it to his family as well. Their results have been nothing short of remarkable. (2)

Before beginning NMN, 47-year-old Sinclair had his blood tested and was told his body had a biological age of 58. After consuming 500 mg of NMN every day for three months, he was tested again and his biological age was 32.

When Sinclair’s mother had her left lung removed, he was told by her doctors that her remaining life expectancy was about a year. Sinclair was not accepting that. He prescribed his mother NMN, and she lived for 20 more years.

Taking NMN has reduced Sinclair’s 77-year-old father’s apparent age by about two or three decades, and he has successfully taken up mountaineering.

Sinclair’s younger brother was so affected by being outpaced by his 77-year-old father that he, too, is now taking NMN.
Ongoing research continues to reveal the numerous anti-aging benefits of NMN. For example, a 2016 study showed that: (3)

NMN suppresses age-associated body weight gain and enhances energy metabolism.
NMN improves insulin sensitivity, eye function, and other features with no toxicity.
NMN prevents age-associated gene expression changes in a tissue-specific manner.
NMN is well-tolerated without any obvious harmful effects.
We Believe Chronic Stress Shortens Telomeres and Makes You Prematurely Old

Dr. Elizabeth Blackburn won a Nobel Prize for her co-discovery of telomerase, the enzyme that replenishes telomeres, the part of chromosomes related to the process of aging. (4)

As we get older, our telomeres shorten. Telomere length is representative of biological age – the age your body thinks it is – as opposed to what the calendar suggests. The shorter your telomeres, the older is your body.

Dr. Blackburn’s research shows that chronic stress disrupts the ability of the enzyme telomerase to help keep telomeres long. If you’re stressed too much for too long, you become older, quicker.

The telomere example underscores the value of choosing the right lifestyle habits, because if you take the time to become mindful of the events that stress you and take actions to mitigate them, then you’re taking an active and positive step to improve your healthspan. In this case, you could meditate and take stress-reducing adaptogens, such as as Ashwagandha and GABA (gamma-aminobutyric acid), the number one inhibitory (calming) neurotransmitter in the brain.

So, yes, we believe supplements make a difference if they’re backed by scientific research. If properly selected, some supplements can help improve our repair mechanisms and/or reduce the damage that accumulates as we age. Take cardiovascular disease, for example, the number one killer worldwide.

We Believe the Risk of Heart Disease Can Be Reduced with Supplements

The risk of dying from cardiovascular disease plummets by more than three-quarters (76%) if you combine healthy eating habits with at least five of six strategies recommended by the American Heart Association. They are: don’t smoke, stay physically fit, maintain a healthy weight, keep blood pressure at 120/80 or lower, be sure total cholesterol is less than 200 and make sure your fasting blood sugar level remains below 100. (5)

Along with these lifestyle factors, certain supplements can help to reduce the risk of heart disease. A 2019 study showed that the probiotic Bifidobacterium longum, CoQ10 and Red Yeast Rice Extract reduced total cholesterol and LDL (the so-called “bad cholesterol”) in people with high cholesterol. (6)

We Believe Polyphenols Can Help Prevent Many Chronic Diseases

A 2015 study showed that certain natural compounds contain the healing properties that may play a preventative role in many of the diseases plaguing us, particularly as we get older.

The compounds that have beneficial biological effects are called polyphenols – including apigenin, epigallocatechin gallate, genistein and epicatechin – and “can be used to treat acute and chronic conditions such as ischemia/reperfusion injury, neurodegeneration, diabetes, and cancer,” the researchers said. (7)

These natural compounds are plentiful in our Green Tea EGCG Extreme™, Pterostilbene Supreme and Natural Resveratrol.

These are all examples taken from scientific studies that show certain supplements can amplify the benefits of lifestyle habits we adopt to extend our healthspan, and perhaps our lifespan as well.

We just need to cross the bridge.

You’re Facing Bridge #1 – Cross It

Ray Kurzweil, American inventor, author and futurist, came up with a metaphor that we think is useful for understanding how the human race will be able to extend its longevity. He calls it the “Three Bridges,” each referring to progressive strides science will make in the future to enable us to live longer and healthier than what is currently possible. (8)

The second and third bridges have not yet been built. They are waiting for the necessary longevity biotechnology that can actually repair DNA and reverse chronic disease to be invented and tested.

But the first bridge is right in front of you. You can cross it now.

Bridge #1 is constructed of the lifestyle habits you make to reduce your chances of getting a chronic disease that will eventually kill you. Because, remember, you don’t die because of old age, but because of disease – the deterioration of some biosystem that can no longer support life.

I hope you now have a better understanding of how and why we believe that the right supplements, supported by scientific research, and coupled with healthy lifestyle choices can help you cross that first bridge to greater health, vitality and longevity.

References:

1. Joe Garma: Want 10 Extra Years? It’s Easier Than You Think In The Blue Zones.

2. George Tait Edwards: How To Live A Healthy Long Life.

3. Kathryn F. Mills, et al: Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.

4. The Milken Institute Center for the Future of Aging: The Habits That Can Help You Live Longer.

5. Maureen Callahan: Fifty-something Diet: Boosting Your Longevity Odds.

6. Ruscica, et al: Nutraceutical approach for the management of cardiovascular risk – a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study.

7. Joseph Shay, et al: Molecular Mechanisms and Therapeutic Effects of (−)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration.

8. Joe Garma: Ray Kurzweil’s March To Extend Life.

8 Great Reasons NAD+ is Anti-aging

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Our cells use NAD+ to make sirtuin proteins work to regulate biological pathways and protect cells from age-related decline.Sirtuins play a crucial role in maintaining the length of telomeres, which are DNA strand end caps that keep our chromosomes from unraveling. Scientists have linked long telomeres with longevity.(1)
Unfortunately, our NAD+ levels drop as we age. One reason is that a compound called CD-38 destroys NAD+. This is a good thing if done modestly, because CD-38 keeps our NAD+ from getting too high and impinging on important biochemical processes, such as sleep-wake and hunger cycles. But as we get older, CD-38 gets too ambitious and destroys too much NAD+. The balance is upended, resulting in too much CD-38, and not enough NAD+.

#1 NAD+ Helps Lengthen Telomeres
Inside the nucleus of a cell, our genes are arranged along twisted, double-stranded molecules of DNA called chromosomes. At the ends of the chromosomes are stretches of DNA called telomeres, which protect our genetic data, make it possible for cells to divide, and hold some secrets to how we age.

Each time a cell divides, the telomeres get shorter. When they get too short, the cell can no longer divide; it becomes inactive (senescent) or it dies (apoptosis). This telomere shortening process is associated with aging, cancer, and a higher risk of death.
NAD+ is required for functioning of the sirtuin proteins that help maintain the length of telomeres.
Foods and supplements rich in polyphenols, such as resveratrol and pterostilbene, may activate sirtuins and contribute to extending lifespan, but emerging evidence suggests sirtuins function best when NAD+ is activated.(2)
#2 NAD+ Helps Repair Our DNA
DNA is highly vulnerable to damage, which can include broken DNA strands and gene mutations. As DNA damage accumulates, it contributes to the aging process and can result in specific lifespan-shortening diseases like cancer and weakened immunity.(3)
Our DNA can fight back. When damaged, DNA activates an enzyme known as PARP-1 that carries out DNA repair within cells. To do this, however, PARP-1 relies on NAD+. To carry out its function, PARP-1 consumes enormous amounts of NAD+. As we get older and our NAD+ becomes gradually depleted, the ability of PARP-1 to repair DNA is significantly compromised.(4)(5)
Replenishing NAD+ restores the DNA repair process and prevents cell death under stress.(6)(7)  In two different animal models of neurodegenerative disease, increasing cellular NAD+ reduced the severity of the disorder, normalized neuromuscular function, delayed memory loss, and extended lifespan.(8)
#3 NAD+ Tunes Immune Cell Signaling
As we age, our immune cells become inconsistent––some become overactive (which can contribute to autoimmune disease) and others slow down (which increases the risk of infection). This process, called immunosenescence, is intimately related to mitochondrial function and energy balance, both of which depend on NAD+ activity.
Thus, adequate intracellular NAD+ is vital for youthful cellular energy, a critically important factor in fending off immunosenescence and maintaining defenses against infections and autoimmune disease.
#4 NAD+ Regulates the Energy Enzymes that Fuel Us
A universal feature of aging is the loss of cellular energy, which results in diminished ATP levels and inadequate cellular fuel necessary to power your body. ATP (Adenosine Triphosphate) is the main source of energy for most cellular processes. All living things, plants and animals, require a continual supply of energy in order to function. The energy is used for all the processes required to keep us alive.(9)
One cause of this energy loss is a breakdown in the efficiency of the electron transport chain, the main pathway through which we extract energy from food and of which NAD+ is an essential component. Disorders ranging from obesity and diabetes to bone loss have been associated with loss of this vital pathway.(10)(11)
Studies show that restoring electron transport chain function by raising levels of NAD+ is a rapid and efficient means of promoting the essential enzymes involved in energy extraction and sustaining youthful cell function. This helps to reduce physiological decline and provides protection from age-related disease.(12)(13)
#5 NAD+ Helps Stabilize Chromosomes
Our chromosomes are complex structures housing our DNA. Think of it this way: DNAis in genes; genes are on chromosomes.
Access to DNA strands for “reading out” genetic instructions requires biochemical control of those proteins to make sure each gene functions properly, but like any complex molecular structure, chromosomes can become unstable. Eventually, instability triggers errors in how genes are interpreted, which ultimately contribute to harmful changes in cell function and structure. Aging is accelerated in the presence of increased chromosome instability.(14)(15)(16).
The enzymes involved in sustaining stable chromosomal structures require NAD+ in order to function properly. When sufficiently present, NAD+ contributes to longevity in animal models showing that NAD+ contributes to longevity; whereas when enzymes that require NAD+ to function are inactive, chromosome structure suffers and cells replicate abnormally.(17)
#6 NAD+ Promotes Brain Health
NAD+ appears essential for sustaining brain health due to its effect on neurotransmitters; in fact, it meets the criteria for a neurotransmitter itself.(18)(19)
Neurotransmitters are brain chemicals that relay signals between nerve cells, and thereby help regulate body-wide functions such as mood, appetite, and stress.
#7 NAD+ Supports Cellular Energy Production
NAD+ was first discovered as an important part of the process that channels chemical energy from foods to the ATP fuel our cells require. Recent studies have revealed that NAD+ is itselfa form of “energy currency” similar to ATP, the complex organic chemical that provides energy to drive many processes in living cells.(20)
NAD+ is also a functional signaling molecule in processes related to energy production, including PARP-1 and sirtuins. When DNA damage occurs, PARP-1 consumes large quantities of NAD+, leading to reduced energy production. In addition, high levels of NAD+ can activate sirtuins, permitting them to carry out their metabolic and stress-protective responses and contributing to longevity.(21)
Supporting efficient energy production and adequate ATP levels requires consistent and abundant NAD+. This is critical because as our cellular energy diminishes, so does our life force.
#8 NAD+ Activates Sirtuins, Regulators of Cellular Aging
Proteins called sirtuinsare major regulators of cellular aging because they influence fundamental functions such as DNA repair and inflammatory responses. They also influence whether cells enter a replicative cycle or instead die a programmed death (apoptosis).(26)
Compounds that activate sirtuins are eagerly sought as chemical “fountains of youth.” Familiar supplements like resveratrol, pterbolene and quercetin have been evaluated as promising sirtuin activators.(22) (23)(24)
Sirtuin activation has shown great promise in fighting cardiovascular disease and preserving aging brain function, but these longevity-promoters cannot function without sufficient NAD+.(25)(26)
The bottom line is that NAD+ is needed for sirtuins to function.
References
Courtney Sperlazza: Is NAD+ the Anti-aging Miracle Pill? Here’s What the Science Says.
Shin-ichiro Imai, et al: NAD+ and Sirtuins in Aging and Disease.
Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature.2009;461(7267):1071-8.
Ying W, Garnier P, Swanson RA. NAD+repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochem Biophys Res Commun.2003;308(4):809-13.
Burkle A, Beneke S, Muiras ML. Poly(ADP-ribosyl)ation and aging. Exp Gerontol.2004;39(11-12):1599-601.
Wang S, Xing Z, Vosler PS, et al. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: role of enhanced DNA repair. Stroke.2008;39(9):2587-95.
Pittelli M, Felici R, Pitozzi V, et al. Pharmacological effects of exogenous NAD on mitochondrial bioenergetics, DNA repair, and apoptosis. Mol Pharmacol.2011;80(6):1136-46.
Fang EF, Kassahun H, Croteau DL, et al. NAD+Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell Metab.2016;24(4):566-81.
Paul May, Bristol University: Adenosine Triphosphate (ATP).
Ritov VB, Menshikova EV, Azuma K, et al. Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity. Am J Physiol Endocrinol Metab.2010;298(1):E49-58.
Shum LC, White NS, Nadtochiy SM, et al. Cyclophilin D Knock-Out Mice Show Enhanced Resistance to Osteoporosis and to Metabolic Changes Observed in Aging Bone. PLoS One.2016;11(5):e0155709.
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.
Mills KF, Yoshida S, Stein LR, et al. Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell Metab.2016;24(6):795-806.
Chen M, Huang JD, Deng HK, et al. Overexpression of eIF-5A2 in mice causes accelerated organismal aging by increasing chromosome instability. BMC Cancer.2011;11:199.
Lushnikova T, Bouska A, Odvody J, et al. Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression. Oncogene.2011;30(46):4622-31.
Rao CV, Asch AS, Yamada HY. Emerging links among Chromosome Instability (CIN), cancer, and aging. Mol Carcinog.2017;56(3):791-803.
Fatoba ST, Okorokov AL. Human SIRT1 associates with mitotic chromatin and contributes to chromosomal condensation. Cell Cycle. 2011;10(14):2317-22.
Mutafova-Yambolieva VN. Neuronal and extraneuronal release of ATP and NAD(+) in smooth muscle. IUBMB Life. 2012;64(10):817-24.
Watroba M, Dudek I, Skoda M, et al. Sirtuins, epigenetics and longevity. Ageing Res Rev. 2017;40:11-9.
Scitable: Cell Energy and Cell Functions.
Oka S, Hsu CP, Sadoshima J. Regulation of cell survival and death by pyridine nucleotides. Circ Res. 2012;111(5):611-27.
Rowlands BD, Lau CL, Ryall JG, et al. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism. J Neurosci Res. 2015;93(7):1147-56.
Hung CH, Chan SH, Chu PM, et al. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res. 2015;59(10):1905-17.
Xiao N, Mei F, Sun Y, et al. Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in adipocytes with regulation of AMP-activated kinase and/or sirtuin 1 activity. Planta Med. 2014;80(12):993-1000.
Imai SI, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2:16017.
Rowlands BD, Lau CL, Ryall JG, et al. Silent information regulator 1 modulator resveratrol increases brain lactate production and inhibits mitochondrial metabolism, whereas SRT1720 increases oxidative metabolism. J Neurosci Res. 2015;93(7):1147-56.

8 important things to know about NMN

You cannot enjoy robust health if your body doesn’t manufacture energy. Unfortunately, as we age, we gradually become increasingly less energetic simply because our bodies produce less of it.

NMN may be a way to cheat Father Time.

Led by Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine, researchers at Washington University School of Medicine in St. Louis have shown that supplementing healthy mice with a natural compound called NMN can compensate for this loss of energy production, reducing typical signs of aging such as gradual weight gain, loss of insulin sensitivity and declines in physical activity.(1)

In skeletal muscle, the investigators discovered that NMN administration helps energy metabolism by improving the function of mitochondria, which operate as cellular power plants.

They also found that mice given NMN:

  • Gained less weight with aging even as they consumed more food, likely because their boosted metabolism generated more energy for physical activity;
  • Gained better function of their retina, as well as increased tear production (often lost with aging);
  • Developed improved insulin sensitivity, and this improvement remained significant even when they corrected for differences in body weight.

#1. Sublingual NMN is the Best NAD+ Booster

The remarkable things that NMN can do to improve your health and help you age better is due to its ability to boost NAD+, and that best happens when the NMN can actually enter your bloodstream.

As you’ll see in the next section, NAD+ (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells, and is necessary for the fundamental biological processes that make life possible.

NAD+ has two general sets of reactions in the human body: helping turn nutrients into energy as a key player in metabolism and working as a helper molecule for proteins that regulate other biological activity. These processes are incredibly important because they are responsible for regulating oxidative stress and circadian rhythms while maintaining the health of DNA and keeping humans healthier for longer.

Unfortunately, NAD+ levels decline as we age, and we simply can’t consume this molecule directly to make up for its decline in our body. That’s why we need to take an NMN sublingual precursor to NAD+ that will boost its levels.

NMN Needs To Enter Your Bloodstream

Taken in a capsule, NMN is primarily digested in the gastrointestinal tract and processed in the liver. However, in sublingual form – where it’s dissolved under your tongue – NMN can bypass the stomach and liver and circulate in your blood where it’s needed. (2)

The absorption of molecules delivered through the sublingual route can be 3 to 10 times greater than oral route delivered via capsule, and is only surpassed by direct IV injection.(3)

#2. NMN Can Reverse Aging of Blood Vessels and Grow Muscle

Vascular aging causes many diseases – cardiovascular, neurological, muscle wasting, frailty, and even aging. As we age, the smallest blood vessels in our bodies wither and die, reducing the blood flow to organs and tissues.

Harvard professor, Dr. David Sinclair’s experiments with mice have demonstrated a way to reverse blood vessel aging and grow muscle.

Dr. Sinclair is among the most renowned anti-aging scientists in the world, and is an expert on NAD+ and NMN. He reports that the NAD+ boosting NMN compound reverses aging in blood vessels and restores muscle strength, while increasing exercise endurance.(5)

A 2018 research study used NMN as the precursor to increase NAD+ levels. Commenting on the study, Dr. Sinclair said:

“We’ve discovered a way to reverse vascular aging by boosting the presence of naturally occurring molecules in the body that augment the physiological response to exercise” adding, “The approach stimulates blood vessel growth and boosts stamina and endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging.”(6)

Old blood vessels become deaf to the signals from exercise muscles, which results in muscles shrinking as we age and a diminished capacity to exercise and grow new blood vessels.

This muscle tissue loss and weakness that happens as we grow older is a condition called sarcopenia. Physically inactive people can lose as much as 3% to 5% of their muscle mass each decade after age 30.

At some point from 75 onward, some amount of muscle attrition occurs even with exercise. Any loss of muscle matters because it lessens strength and mobility, often leading to instability and a higher chance of falling.(7)

Cognizant of the effects of sarcopenia, Dr. Sinclair and his research associates decided to examine why exercise loses its protective power to sustain muscle vitality and whether this process is reversible.

The signaling crosstalk between blood vessels and muscles requires NAD+ and sirtuin1, or SIRT1. NAD+ boosts SIRT1, which in turn enables the signaling conversation between muscles and blood vessels. The problem is that both NAD+ and SIRT1 decline as we age and eventually can no longer perform their role as the interface between muscles and blood vessels.

In Dr. Sinclair’s study, mice were given NMN which boosted NAD+ levels and in turn boosted SIRT1. The results were that these mice had better endothelial function, blood vessel growth and improved blood supply to their muscles.

#3. NMN Can Lower Your Body Fat

Weight gain and weight loss resistance are common struggles for countless people across the world. NMN is a powerful nutraceutical ally in weight loss efforts because it reverses insulin resistance, improves glucose tolerance, and ameliorates mitochondrial dysfunction, three factors that contribute to stubborn weight issues.

Shin-ichiro Imai, MD, PhD from the Washington University School of Medicine conducted an experiment on mice to see if NMN could augment their NAD+ levels by converting NMN to NAD. The results were so startling that Timemagazine wrote a feature article about the experiment.(8)

Remarkably, this study showed that old mice could be made young, thin, and energetic again with NMN. The researchers showed, at least in mice, aging could be reversed with NMN supplementation.(9)

In Dr. Imail’s study, mice fed low-dose NMN lost 4% of their body weight. Those fed high-dose NMN lost 9% of their body weight.

#4. NMN Can Increase Your Energy

The mitochondria are the energy power plants of cells. In Dr. Imai’s study, mice given NMN were much more energetic and had better energy production from their mitochondria.

Indeed, the most important NAD+ precursor for mitochondrial synthesis is NMN.(10)

During the course of Dr. Imai’s experiment, NMN-consuming mice switched their primary energy source from glucose to fatty acids. The overall results from the experiment “strongly suggest that NMN has significant preventive effects against age-associated impairment in energy metabolism…”(11)

#5. NMN Can Improve Your Insulin Sensitivity

Mice on NMN showed much better insulin sensitivity. Better insulin sensitivity means less diabetes. Even heavier mice on NMN showed better insulin sensitivity.

Consistent with these insulin results, after 12 months of NMN administration, NMN-fed mice showed significantly improved insulin sensitivity compared to the body weight-matched control group.(12)

#6. NMN Can Improve Your Heart

The human heart requires a continuous supply of ATP to fuel its muscular contractions and sustain life. ATP is short for Adenosine Triphosphate, a molecule known in biochemistry as the “molecular currency” of intracellular energy transfer; meaning that ATP stores and transports chemical energy within cells.

Without ATP we would soon die, but that doesn’t happen. What does happen is Interruptions in the heart’s ATP supply, which can impair cardiac and vascular function and contribute to the development of cardiovascular disease.

By enhancing the biosynthesis of NAD+, an essential substrate in ATP-producing reactions, NMN boosts cardiac ATP levels and significantly improves heart health. Importantly, NMN also reduces arterial aging and vascular dysfunction, two phenomena that play crucial roles in the pathogenesis of cardiovascular disease.(13)

#7. Alzheimer’s Symptoms Improved with NMN

Alzheimer’s is a chronic neurodegenerative disease that usually starts slowly and worsens over time. It is the cause of 60 to 70% of cases of dementia. The most common early symptom is difficulty in remembering recent events or newly learned information (short-term memory loss).

Although nearly 60% of the world’s population thinks that Alzheimer’s is a typical part of aging, it is not. It can be avoided.(14)

For most people, scientist think that Alzheimer’s disease is caused by a combination of genetic, lifestyle and environmental factors that affect the brain over time, with genetics being the most minor cause; just 1%.(15)

The exact causes of Alzheimer’s disease aren’t fully understood, but at its core are problems with brain proteins that fail to function normally, disrupt the work of brain cells (neurons) and unleash a series of toxic events. Neurons are damaged, lose connections to each other and eventually die.

The damage most often starts in the region of the brain that controls memory, but the process begins years before the first symptoms. The loss of neurons spreads in a somewhat predictable pattern to other regions of the brains. By the late stage of the disease, the brain has shrunk significantly.

The good news is that NMN may help decrease the causes of Alzheimer’s. A study published in 2107 concluded that:

“NMN decreased β-amyloid production, amyloid plaque burden, synaptic loss, and inflammatory responses in AD-Tg mice.” [Mice that mimic a range of Alzheimer’s disease-related pathologies.] (16)

#8. NMN Can Help Repair DNA

Your DNA is the blueprint for your body’s physiological function. When proper DNA expression is altered because of an unhealthy diet, environmental toxins and aging, then your body’s DNA blueprint can be altered. Should this happen, chronic health conditions can develop, such as cancer, diabetes, and neurological dysfunction. NMN helps prevent adverse changes in gene expression by repairing damaged DNA.(17)


References

  1. Science Daily: Natural compound reduces signs of aging in healthy mice.
  2. Ling Liu: Quantitative Analysis of Redox Metabolism.
  3. Neha Narang, Jyoti Sharma: Sublingual Mucosa As A Route For Systemic Drug Delivery.
  4. Healthline: Xylitol, Everything You Need to Know.
  5. David Sinclair, et al:Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging
  6. EKATERINA PESHEVA: Rewinding the Clock
  7. WebMD: Sarcopenia With Aging.
  8. Alice Park: How This Broccoli Enzyme Can Slow Aging.
  9. Shin-ichiro Imai, et al: Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.
  10.  Antonio Lucena-Cacace, et a: Nicotinamide phosphoribosyltransferase: Biology, role in cancer, and novel drug target.
  11.  Shin-ichiro Imai, et al: Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.
  12.  Ibid
  13.  Yamamoto T, et al: Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion.
  14.  Alzheimer’s Association: https://www.alz.org/news/2014/nearly-60-percent-of-people-worldwide-incorrectly
  15.  Mayo Clinic: Alzheimer’s Disease.
  16.  Yao Z, et al: Nicotinamide mononucleotide inhibits JNK activation to reverse Alzheimer disease.
  17.  Jun Li, et al: A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.