Life Extension Magazine®

Issue: Feb 2019

Power a Longer Life via NAD+ Restoration

A coenzyme called NAD+ supports DNA repair and other youthful processes. Restoring NAD+may halt certain degenerative factors, boost brain function, and reduce risk for age-related disorders.

By Gene Richmond

In year 2001, Life Extension® researchers actively sought a method to boost levels of a coenzyme in aging people.

We knew this was critical to achieving healthy longevity.

Consumers had to wait until 2014 for a validated method to become available.

This coenzyme is called NAD+ and is vital for energizing cells and supporting youthful cellular processes.1-4

For resveratrol users, NAD+ is especially important.

That's because resveratrol promotes expression of cell proteins called sirtuins that protect against age-related decline.3-7

But sirtuins need NAD+ to function.

What you need to know

  • Every cell in the body relies on NAD+ both to maintain normal energy supply and to protect the cell.
  • Sirtuins, proteins critical for maintaining optimal health and longevity, are completely dependent on adequate levels of NAD+ to function optimally.
  • As we age, our NAD+ levels and sirtuin activity decline.
  • Interventions to boost NAD+ levels in cells have demonstrated promise in extending life and preventing loss of function.
  • Nicotinamide riboside is an NAD+ precursor that is readily absorbed from the gut and is effective at boosting levels of NAD+ in cells throughout the body.

And as we age, NAD+ levels drastically plummet. 6-8

The result is loss of cellular functions and potential accelerated aging.

A patented supplement called nicotinamide riboside replenishes cellular NAD+.

Studies reveal how restoring NAD+ may slow or halt certain aging processes, boost brain function, and reduce risk for age-related disorders.3,7,9

NAD+ and Brain Function

Longer life means little without an enhanced healthspan as well. Fortunately, boosting levels of NAD+ in later life maximizes healthy function and can prevent degenerative disorders.

A major cause of diminishing life quality in older age is loss of cognitive function and dementia.

Research has found that supporting healthy levels of NAD+ has neuroprotective effects, guarding against age-related loss of brain function including traumatic injury and stroke.10-23

Two recent studies utilized experimental mouse models of Alzheimer's disease, the most common cause of dementia in older adults.10,12 These mice display changes in the brain similar to those observed in elderly humans, and could be expected to result in significant deficits in cognition.

Impact of Severe NAD+ Deficit
Shaded DNA strand becoming a human
  • Tremors
  • Depression
  • Arterial Stiffness
  • Circadian Rhythm Imbalance
  • Pro-youth Genes Turned Off
  • Restless Leg Syndrome
  • Cellular Senescence
  • Sarcopenia
  • Death

In both studies, giving the mice nicotinamide riboside supplements stopped the decline of NAD+ levels in the brains—and greatly reduced cognitive deterioration.

The studies also showed reduced evidence of DNA damage in brain cells, reduced inflammation, and signs that synaptic plasticity was restored. Synaptic plasticity (the ability of the brain to adapt and maintain healthy connections) is typically impaired in older age and in cognitive disorders like dementia.

Another remarkable two-pronged study showed that nicotinamide riboside helps protect against the effects of Parkinson's disease.17

In the first part of the study, using a fly model of Parkinson's, nicotinamide riboside prevented the death of nerve cells in the brain and preserved motor function. In the second part, using human brain cells harvested from Parkinson's disease patients, the supplement raised levels of NAD+ and caused improvements in mitochondrial
function.17

The study researchers concluded that nicotinamide riboside is a promising approach to protecting against Parkinson's disease and likely other degenerative diseases of the nervous system.

Obesity, Metabolism, and Cardiovascular Function

Magnifying glass overlooking cellular strands

Obesity, diabetes, and metabolic syndrome are common age-related issues. Along with other factors, these conditions put people at risk for cardiovascular disease, cancer, and kidney failure.

NAD+ is crucial to basic metabolic functions and cellular integrity. Several studies confirm that raising levels of NAD+ increases metabolism and may help prevent and treat obesity, fatty liver disease, diabetes, and metabolic syndrome.24-28

That's where nicotinamide riboside comes in. By stimulating levels of NAD+, nicotinamide riboside enhances metabolism. In mice, it increases metabolic rate, raising body temperature slightly and reducing deposits of abdominal fat, which is tied to high risk for cardiovascular disease.29

Even in rats fed a high-fat diet, nicotinamide riboside boosts metabolism and prevents obesity.25,30

In mice suffering from prediabetes and diabetes, it improves control of blood sugar and reduces weight while protecting against tissue injury such as liver damage and nerve disease.27

The potential benefits for humans are extraordinary. Both by improving metabolic health and by its direct effects on the heart muscle and blood vessels, nicotinamide riboside shows promise in preventing cardiovascular disease.31

That's remarkable enough. But nicotinamide riboside supplements have also shown promise as a treatment for heart disease by raising levels of NAD+, known to be vital for normal heart function and recovery following an injury.32-34

In one study, mice with cardiac disease and heart failure were protected by nicotinamide riboside.32 While untreated animals rapidly developed dilation of the heart, thinning of the heart muscle, and decreased cardiac output—often seen in human heart disease—animals given supplements of nicotinamide riboside maintained cardiac muscle integrity and function.

NAD+ and Longevity

IMAGE DESCRIPTION HERE

There are a number of known behaviors one can make to extend a healthy lifespan.

These include a wholesome diet, avoidance of toxins, intake of inflammation-suppressing nutrients, and regular exercise.

Recent studies show promise for a more targeted approach to increasing longevity.

Sirtuin activity is a crucial component to living a longer life.

As NAD+ levels fall and sirtuin activity wanes, aging becomes more evident as follows:

  • Diminished brain function,35,36 leading to cognitive decline and risk for dementia.
  • Inflammation in blood vessels that contributes to atherosclerosis and cardiovascular disease.37,38
  • Fatty changes in the liver that leads to non-alcoholic fatty liver disease (NAFLD).39-41
  • Increased fat storage,42,43 that leads to overweight and obesity. When fat is stored around the liver and other organs, it increases systemic inflammation and contributes to metabolic and cardiovascular disease.
  • Insulin resistance, impairing the metabolism of glucose and leading to metabolic syndrome and diabetes.38,44,45
  • Muscle changes, including loss of muscle strength, fat deposits in muscles, and fatigue. 46

Studies show that enhancing sirtuin activity promotes longevity.5-7,9,38,47,48 Sirtuin activity is vitally dependent on NAD+, so boosting the body's NAD+ levels as we age may help prolong life.

This has been demonstrated in a wide variety of living organisms.49,50

Yeast grown with nicotinamide riboside have an increase in lifespan.51 In one study, worms given nicotinamide riboside lived 16% longer.52

Even in already elderly mice, a study by an international team of scientists published in Science showed that nicotinamide riboside extends lifespan by nearly 5%.53 This is at an age where other treatments attempting to prolong life fail. Scientists also observed several biochemical changes in these animals, indicating rejuvenation of cell function.

NAD+ May Improve Heart Function

"Stabilizing the intracellular NAD+ level represents a promising therapeutic strategy to improve myocardial bioebergetics and cardiac function."

"In this issue of Circulation, Diguet, et al report exciting data suggesting that supplementation with NAD+ precursor, nicotinamide riboside, reduces cardiac dysfunction in preclinical models of heart failure."

— May 22, 2018 http://circ.ahajournals.org/content/137/21/2274

NAD+ and DNA Repair

The DNA in our cells suffers considerable damage every day. The only reason this does not kill us is that cells are very efficient at repairing this damage, which comes in the form of single- and double-strand DNA breaks.

As NAD+ levels decline with age, we are less able to repair cellular DNA.

For example, sirtuins protect DNA from damage that can lead to potentially harmful mutations. Threats to DNA increase significantly with age. Protective sirtuin proteins must operate at full strength in order to properly safeguard DNA, shielding against age-related loss of function and risk for cancer.

In fact, research has demonstrated that dwindling sirtuin activity is associated with more rapid aging—and that boosting sirtuin activity is protective, prolonging lifespan and guarding against disease.9

But sirtuins require NAD+ to function. An ample and continuously renewing supply of NAD+ is needed by the cell to keep operating normally.

Since NAD+ levels diminish with advancing age, replenishing our NAD+ supply is essential to any plan to forestall aging and degenerative disease.9

NAD+ Needed for DNA Repair
artistic image of DNA strand
  • Each cell in your body suffers 10 DNA breaks every day.*
  • Unrepaired DNA damage is a major degenerative aging factor.
  • NAD+ depletion with aging turns off DNA repair enzymes.

* Lieber, MR. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem. 2010;79:1281-211.

Nicotinamide Riboside Boosts NAD+

A proven method of boosting NAD+ levels in the body is to supply cells with precursor compounds that naturally convert to NAD +.

One way to do this is with nicotinamide riboside. This naturally occurring form of vitamin B3 is only found in trace amounts in the diet. Therefore, the only way to significantly raise its intake is through supplementation.

Research shows that when taken by mouth, nicotinamide riboside is highly bioavailable, and has been shown to boost NAD+ levels in the body.54

One study showed that compared to baseline, daily supplementation with 250 mg or 500 mg of nicotinamide riboside for 4 weeks increased NAD+ blood levels by approximate 40% and 90% respectively.55

NAD+ Sharply Plummets with Age
Life Extension Magazine cover September 2017
  • At age 50, we have 40% less NAD+ than at age 20.
  • By age 80, NAD+ levels drop as much as 98%.

* The Plasma NAD+ Metabolome is Dysregulated in "Normal" Aging. Rejuvenation Research. 2018 Oct 23, and unpublished clinical observations.

 

 

 

Summary

NAD+ is a vital cofactor for energy metabolism and hundreds of longevity-promoting processes in every cell of the body.

Aging is associated with reduced NAD+ levels. This decline is a major contributor to the aging process and puts cells and tissues at risk for age-related injury and loss of function.

Nicotinamide riboside is a readily absorbed compound that helps cells maximize their supply of NAD+ to help maintain DNA repair.

Human studies show that nicotinamide riboside is highly bioavailable and rapidly increases NAD+ in cells.

Boosting NAD+ to more youthful levels with nicotinamide riboside has been demonstrated to prolong life and reverse loss of function in animal models.

What Are Sirtuins and Why Are They So Powerful as an Anti-Aging Target?

Sirtuins are regulatory proteins in all cells that play a critical role in the response to stress and injuries that cause damage, particularly DNA damage.6,7

Over a lifetime, cells accumulate damage, which can lead to loss of function and risk for disease.

Without mechanisms to defend against and repair this damage, cells rapidly age and become dysfunctional. That is where sirtuins come in.

Activated sirtuins help initiate repair of DNA, preventing the development of dysfunctional genes and mutations.

Sirtuins are also involved in the body's internal clock, the circadian rhythm, which is crucial to maintaining a healthy metabolism. Defects in this clock have been associated with premature aging and disease.

Therefore, maintaining optimal sirtuin activity is one the body's best defenses against the ailments and illnesses associated with aging. But sirtuins require NAD+ to function normally.

Advancing age leads to accumulating DNA damage. As sirtuins use NAD+ to fight this damage, the body's supply of NAD+ is depleted. The resulting low NAD+ levels then impair the ability of sirtuins to continue functioning normally, leading to further DNA damage.

A powerful way to break this cycle is to replenish the body's levels of NAD+.

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

 

References

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