As we age, the tiniest blood vessels in our bodies become damaged, wither and die, and our arteries harden and become less pliable. When this happens the blood flow to organs and tissues is reduced, leading the way to many diseases - cardiovascular, neurological, muscle-wasting frailty and even aging itself.
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 2018 showed 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 Sinclair summarize 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."
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)
Interestingly, Dr. Sinclair and his family are not waiting for an NMN-based drug to be developed. What they are doing is taking an NMN supplement every morning, the same NMN offered by Prohealth's NMN Pro Powder.
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 function begins 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 Syndrome is 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 injury is the tissue damage caused when blood supply returns to tissue after a period of ischemia or lack of oxygen. (4)
Cardiomyopathy refers 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)
Dyslipidemia is 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.
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)
Joe Garma has written more than 670 articles on his anti-aging blog, GarmaOnHealth, and is currently writing a book, The Ageproof Method, 12 Biohacks for A Long and Strong Life. Prohealth Longevity readers can get his four-part guide, Transform Your Body and Mind here.
- Ekaterina Pesheva: Rewinding the Clock
- Cedars-Sinai Medical Center: Endothelial Function Testing
- Mayo Clinic: Metabolic syndrome
- Wikipedia: Reperfusion injury
- Heart.org: What Is Cardiomyopathy in Adults?
- Wikipedia: Dyslipidemia
- 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
- The Jackson Laboratory: Why are mice considered excellent models for humans?
- Brady Hartman: Dr. David Sinclair, Discoverer of Anti-aging NAD Fad, Speaks About Human Trials of NMN
- Joe Rogan Experience #1234: David Sinclair
- Alice Park: This Compound Can Reverse Aging in Mice. Will It Work in People?
- Innovation Toronto: NMN reduces signs of aging: It's safety is being tested