Health & Fitness

The tendency is to lose muscle as you age, a condition known as sarcopenia. If you don’t do anything to stop it you can expect to lose about 15% of your muscle mass between your 30s and your 80s.¹ An estimated 10% to 25% of seniors under the age of 70 have sarcopenia and as many as half those over the age of 80 are impaired with it.²

Enforced bedrest, due to hospitalization, for example, can also have a dramatic impact on your muscle mass, even if you’re younger. According to a 2015 review³ in Extreme Physiology & Medicine, you can lose 5.2% of your muscle mass in the first two weeks of bedrest. By Day 23, you can have lost up to 10% of your quadriceps muscle mass.

Not only are strong muscles a requirement for mobility, balance and the ability to live independently, but having reserve muscle mass will also increase your chances of survival⁴ when sick or hospitalized. Since muscle is lost far more easily and quicker than it’s built, finding ways to continuously promote and maintain your muscle mass is of utmost importance.

The Crucial Role of NAD+

As reported by Science Daily,⁵ scientists recently discovered that Alzheimer's-like protein aggregates underlie the muscle deterioration commonly seen in aging, and that nicotinamide adenine dinucleotide (NAD+) is essential for combating this condition.

Their study,⁶ published in the journal Cell Reports, showed that protein aggregates (amyloid) could be blocked by boosting the levels of NAD+, a biomolecule that is also essential for maintaining mitochondrial function.

Higher levels of NAD+ were found to turn on the defense systems of the mitochondria and restore muscle function. Aggregated proteins have long been thought to be a contributor to brain aging, and this study proves aggregated proteins also contribute to muscle aging.

"The most prominent component of these protein aggregates is beta-amyloid, just like in the amyloid plaques in the brains of patients with Alzheimer's disease," said Johan Auwerx at EPFL's School of Life Sciences. "These abnormal proteotoxic aggregates could serve as novel biomarkers for the aging process, beyond the brain and muscle."

The study points out that NAD+ homeostasis is required to maintain proteostasis, i.e., the regulation of protein creation, folding, trafficking and degradation. It turns out that boosting NAD+ in later life will reduce amyloidosis (the buildup of amyloid) and mitochondrial dysfunction.

The importance of NAD+ for healthy muscle function is also reviewed in “Sarcopenia and Muscle Aging: A Brief Overview,”⁷ published in the journal Endocrinology and Metabolism. The paper highlights:

“… recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD+) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle.”

As indicated by the Cell Report study, this Endocrinology and Metabolism paper highlights the connection between sarcopenia and mitochondrial dysfunction in both skeletal muscle and motor neurons.

People with sarcopenia have been found to have both reduced mitochondrial oxidative capacity and inhibited NAD+ biosynthesis, and several studies have proposed that mitochondrial dysfunction in your neurons actually drive the development of sarcopenia.⁸

What Is NAD+?

NAD+ is a substrate for a number of important enzymes, including poly(ADP-ribose) polymerase (PARP) and sirtuin 1 (SIRT1), which is known as a classic longevity protein. NAD+ is also essential in metabolic processes such as creating ATP in your mitochondria. It accepts and donates electrons and is used in oxidation-reduction reactions in the mitochondrial electron transport chain.

Interestingly, what scientists have observed is that NAD+ levels decline in most tissues over time, and is associated with aging in general and is therefore thought to play an important role in many age-related diseases.

According to the Endocrinology and Metabolism paper,⁹ researchers have shown that when the NAD+ salvage pathways in muscle are impaired, mitochondrial dysfunction and decreased muscle mass ensues.

NAD+ boosting molecules such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide (a form of vitamin B3 or niacin) and nicotinic acid (niacin) have all been shown to protect against age-related muscle disease.

How to Boost NAD+

Of those four, NMN is my personal favorite as it activates the NAD+ salvage pathway. As explained by Siim Land in a recent interview, featured in “Simple Strategies That Will Improve Your Immunity,” which also reviews the importance of NAD+ in COVID-19:

“A lot of the NAD that your body produces is recycled through the salvage pathway. Very little (less than 1%) of it is going to come from food, especially tryptophan or niacin. The easiest way to prevent losing your NAD as you get older or as you get immunocompromised is to promote the salvage pathway.”

I’ve previously recommended the use of NR over NMN but have since changed my stance. NR used to be considered superior because no NMN transporter — required to get it into cells — had been detected. We now know there is such a transporter, which gives NMN the advantage as it’s also a more direct NAD+ precursor.

Most of the NAD+ precursor research is done with NR and that used to be my primary choice. However, as you can see from the image above, NMN converts to NAD+ whereas NR must first be converted into NMN before it can be converted into NAD+,¹⁰ so it makes more sense to use NMN for NAD+ augmentation.

The image above also shows how niacin (NA) also finds its way to become NAD+. Niacin is also a useful supplement to use in increasing NAD+ levels. You just need to limit the dose to about 25 mg, which most is a dose low enough not to cause any flushing. Higher doses are not likely as effective as NMN and exercise in producing NAD+.

The NMN transporter was discovered^11,12 shortly before my interview with David Sinclair, Ph.D., a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. Interestingly, NMN is also Sinclair’s favorite NAD+ precursor.

Sinclair is generally acknowledged for bringing the importance of NAD+ to the world with his experiments at MIT in the late ‘90s which connected NAD+ to sirtuin activation. We discuss these issues in “The Revolutionary Science of Aging and Longevity,” the interview from which is embedded above for your convenience.

I believe one of the most effective ways of boosting your NAD+ level is to use NMN in suppository form, as this allows you to avoid most of the methylation of the supplement. Other alternatives include subcutaneous or intranasal administration, all of which are more effective than oral supplements.

Unfortunately, NMN is not sold in suppository form, so you would need to get silicone candy molds and use coconut oil to serve as binder for the NMN. The suppositories would need to be refrigerated as coconut oil tends to melt at 75 degrees Fahrenheit. Additionally, NMN is quite perishable, which is another reason to refrigerate it.  

As for the other NAD+ boosters, I do not recommend using high-dose niacinamide because in high doses it inhibits Sirt1, an important longevity protein. As mentioned above, low-dose niacin (vitamin B3) of 25 mg can be used.

Low doses of niacin, along with NMN in suppository form — both of which are precursors to NAD+ — are typically sufficient. As an added boon, raising your NAD+ also appears protective against severe COVID-19, as detailed in “Is Niacin a Missing Piece of the COVID Puzzle?” There are also NAD+ supplements available, but their price tags can be prohibitive.

Lifestyle Strategies Can Address Underlying Cause of Low NAD+

While supplements such as NMN can certainly be helpful, if your NAD is low, your best bet is really to address the underlying cause. The good news is that this can be done through simple lifestyle strategies such as exercise, sauna bathing, fasting, realigning your circadian rhythm and minimizing electromagnetic field (EMF) exposure.

One of the reasons exercise, heat exposure and fasting work to address low NAD+ levels is because they are catabolic stressors that activate AMP protein kinase (AMPK). AMPK, in turn, activates an enzyme called NAMPT, which governs the NAD+ salvage pathway.

Blood flow restriction (BFR) training can be particularly beneficial in terms of exercise. It has been shown to naturally increase your NAD level and is very safe for the elderly. You can learn more about this in “BFR Training for Muscle Mass Maintenance.”

Your circadian rhythm, meanwhile, plays a role because it is controlled by longevity genes called sirtuins, SIRT1 in particular. If your circadian rhythm is misaligned, then sirtuins are not expressed, which in turn inhibits NAMPT, thereby shutting down your NAD+ salvage pathway.

Oxidative stress and inflammation also use up and deplete NAD+, and exercise, sauna and fasting all help to reduce these. As a result, less NAD+ is depleted. So, these strategies not only improve your NAD+ production, but also reduce your body’s NAD+ consumption. The end result is a higher NAD+ baseline.

EMF exposure, which is the topic of my book “EMF*D,” is one common source of oxidative stress, so it too increases your NAD+ consumption. It does this by activating PARP, a DNA repairing enzyme. Each time PARP is activated, it uses up 150 molecules of NAD+. Hence, reducing your EMF exposure can also be an important strategy to preserve and protect your NAD+ level.

Your body also uses up NAD+ to detoxify alcohol, so if nightly drinking is part of your routine, consider giving it up. To learn more about how healthy lifestyle strategies such as the ones mentioned here can improve your NAD+ level, consider reading through the paper “Healthy Lifestyle Recommendations: Do the Beneficial Effects Originate from NAD+ Amount at the Cellular Level?”¹³

NAD+ Is a Crucial Antiaging Component

So, to summarize, raising your NAD+ level and keeping it high has many important health benefits, from supporting mitochondrial function, which is crucial for general health and longevity, to protecting against severe COVID-19 and age-related muscle loss.

The great news is that this can easily be done by implementing the healthy lifestyle strategies reviewed above — exercise, sauna, fasting and recalibrating your circadian rhythm — while simultaneously avoiding things that deplete your body of NAD+, such as EMF exposure and excessive alcohol consumption. On top of that, supplements such as NMN together with normal doses of niacin can help boost your NAD+ in the short term.

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Hyperbaric oxygen treatment may be a practical method for slowing down the hands of time. At its foundation, aging represents a progressive loss of physiological capacity, researchers from Tel Aviv University and the Shamir Medical Center in Israel explained in the journal Aging.¹

The biological deterioration leads to impaired functions and increased vulnerability to diseases, including cancer, heart disease, diabetes, Alzheimer’s disease and others.

Hyperbaric oxygen treatment (HBOT), the Aging study suggests, may target two cellular hallmarks of aging — shortening of telomeres and cellular senescence, or the loss of a cell’s ability to divide and grow — thereby reversing signs of the aging process in humans.²

Sixty Hyperbaric Oxygen Sessions Slow Down Aging

The research team has been exploring the benefits of exposure to high-pressure oxygen at different concentrations inside a pressure chamber for years, with studies showing such treatments improved stroke, brain injury and brain function that was damaged by aging.³

The current study looked at hyperbaric oxygen treatment on healthy adults aged 64 and over to determine its effects on the normal aging process at a cellular level.

Thirty-five subjects were exposed to a series of 60 hyperbaric oxygen sessions over a 90-day period. Blood samples, which were analyzed for immune cells, were collected before, during and after the treatments. Two exciting results were found:⁴

• Telomeres at the end of chromosomes grew longer instead of shorter, at a rate of 20% to 38% depending on the type of cell
• Senescent cells decreased significantly, by 11% to 37% depending on cell type

In a Tel Aviv University news release, study author Dr. Shai Efrati of the university’s Sackler School of Medicine, explained:

“Today telomere shortening is considered the ‘Holy Grail’ of the biology of aging. Researchers around the world are trying to develop pharmacological and environmental interventions that enable telomere elongation. Our HBOT protocol was able to achieve this, proving that the aging process can in fact be reversed at the basic cellular-molecular level.”

Telomeres and Cellular Senescence: Keys to Aging?

Telomeres are repetitive nucleotide sequences at the end of each chromosome. Sometimes compared to the plastic tip on a shoelace, telomeres help protect DNA, preserving chromosome stability and preventing “molecular contact with neighboring chromosomes.”⁵

Evidence suggests telomere length may predict morbidity and mortality, with shorter telomeres linked to an increased risk of premature death,⁶ but the link is controversial.

“This uncertainty is actually due to a kaleidoscope of biological and technical factors, including preanalytical issues (e.g., sample matrix), poor standardization of techniques used for their assessment, and dependence of telomere structure upon genetics, epigenetics, environment and behavioral attitudes, which may be present at a variable extent in various physiological or pathological conditions,” researchers wrote in the Annals of Translational Medicine.⁷

Still, despite the controversy, telomere shortening has been associated with a 23% higher risk of all-cause death, along with increased risk of certain cancers, including glioma, neuroblastoma, ovarian, endometrial, lung, kidney, bladder, skin and testicular.⁸

Telomere shortening is also said to represent a “major measurable molecular characteristic of aging of cells in vitro and in vivo,” which may have developed as a mechanism to protect against tumors in long-lived species.⁹

Dr. Amir Hadanny, chief medical research officer of the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center, an author of the featured study, added that lifestyle modifications and intense exercise have previously been found to slow telomere shortening, but HBOT appears to be another viable option:¹⁰

“In our study, only three months of HBOT were able to elongate telomeres at rates far beyond any currently available interventions or lifestyle modifications. With this pioneering study, we have opened a door for further research on the cellular impact of HBOT and its potential for reversing the aging process.”

Cellular senescence is also known to play a role in cellular aging, and the accumulation of senescent cells is believed to be an integral part of the aging process, even potentially acting as a causal factor in age-related disease.¹¹

Research is underway to develop therapeutic strategies to interfere with cellular senescence, including eliminating senescent cells,¹² and HBOT has emerged as one potential strategy.

Not Necessarily a Clear-Cut Fountain of Youth

It’s important to take the study’s limitations into account when evaluating whether HBOT is truly a fountain of youth, as the researchers imply. It was a small study, which means the results should be replicated in a larger sample of subjects.

Also, as mentioned, the use of telomere length as a marker for aging is in itself controversial. The study also measured telomere length on immune cells called T cells, which may fluctuate depending on a number of environmental conditions, such as exercise.

It’s a positive sign that HBOT also decreased cellular senescence in T cells, but as noted by Steve Hill, who serves on the board of directors for LEAF, a nonprofit promoting increased healthy human lifespan:¹³

“The problem with interpreting these results as rejuvenation or age reversal is that T cells are a poor choice of cell type to use for this kind of thing due to their highly dynamic nature. Unfortunately, they are a popular cell type to use in these sorts of studies, due to the ease of collection from the bloodstream.

These particular immune cells can have large variance in their telomere length based on the demand for cellular replication at that particular time.

T cell populations replicate rapidly in the face of pathogens, and with each replication, the telomeres shorten, meaning that telomere lengths can vary in these cell populations from day to day. Infection and other environmental factors can play a key role in the status of T cell telomeres, and this is why they are not overly useful as aging biomarkers.”

This isn’t to say that HBOT isn’t useful, as other experts agree HBOT can have significant benefits for longevity. One of the reasons I'm fascinated by HBOT, in particular, is because of its ability to improve mitochondrial function.¹⁴ However, it should be viewed as one component of healthy aging, not necessarily a magic bullet that will stop it in its tracks.

How Does Hyperbaric Oxygen Therapy Work?

HBOT has long been used as a treatment for decompression sickness that can occur among scuba divers. When you sit in a hyperbaric oxygen therapy chamber, you breathe air that has two to three times greater air pressure than normal, which allows your lungs to absorb more oxygen.

This, in turn, increases the amount of oxygen in your blood, which is transported throughout your body, fighting pathogenic bacteria and stimulating the release of healing growth factors and stem cells.¹⁵

In my interview in the video above with Dr. Jason Sonners, a chiropractor who has worked with HBOT for over 12 years, he explains that oxygen can be viewed as a nutrient. Your body needs it to carry out its regular functions and, when tissue is injured, it needs even more oxygen for healing.¹⁶

Most healthy individuals have somewhere between 96% and 98% oxygen in their hemoglobin, which means your capacity to increase your oxygen level is between 2% and 4%, were you to breathe medical-grade oxygen, for instance. However, you can increase your oxygen level far beyond that if your body is under pressure. According to Sonners:

"Two main laws govern how that works: Boyle's Law and Henry's Law. Basically, as you take a gas and exert pressure on it, you make the size of that gas take up less space. As a result of that pressure, you can then dissolve that gas into a liquid.

An easy example is a can of seltzer. They're using carbon dioxide and water. But basically, you can pressurize that can, so you can put carbon dioxide into that can. As a result of that pressurization, you can dissolve molecules of carbon dioxide into the water.

In the hyperbaric version of that, we're using oxygen, and the can is the chamber. But as a result of dumping excess oxygen inside that chamber, you can dissolve that into the liquid of your body … directly into the tissue and the plasma of your blood.

The oxygen in your blood is carried by hemoglobin. The plasma that carries your red blood cells that holds the hemoglobin normally does not carry oxygen. We rely wholly on red blood cell oxygen-carrying capacity. But inside the chamber, you could literally bypass the red blood cell oxygen-carrying capacity altogether, and you can absorb oxygen directly into the plasma and tissue of the body."

HBOT Fights Mitochondrial and Oxidative Stresses, COVID-19

HBOT can be used to help speed healing of any inflammatory condition, and it’s known to facilitate wound healing and cell survival.

A small study involving 10 healthy men also revealed that a single 45-minute HBOT session reduced levels of metabolic stress-related biomarkers, including attenuating mitochondrial and oxidative stresses and relieving metabolic burdens, which suggests it may be useful for treating metabolic diseases.¹⁷

The fact that HBOT protects against mitochondrial dysfunction¹⁸ is a major benefit, considering most chronic and degenerative diseases involve mitochondrial dysfunction. Unfortunately, conventional medicine still reserves HBOT for a limited number of conditions, such as certain brain injuries and serious wounds, as well as the following:¹⁹

Severe anemia	Brain abscess	Bubbles of air in your blood vessels
Burns	Carbon monoxide poisoning	Crushing injury
Deafness, sudden	Decompression sickness	Gangrene
Infection of skin or bone that causes tissue death	Nonhealing wounds, such as diabetic foot ulcer	Radiation injury
Skin graft at risk of tissue death	Traumatic brain injury	Vision loss, sudden

In the U.S., there are only 14 conditions for which insurance will pay for HBOT, whereas there are up to 100 approved indications for HBOT internationally, according to Sonners.

From my perspective, it's medically reprehensible and inexcusable for a doctor to not treat patients with diabetic neuropathy, infections in the distal extremities or peripheral vascular disease with HBOT, as it will in most cases prevent the need for amputation. Other conditions that may benefit from HBOT include:

All autoimmune conditions

Neurological conditions, including concussion, traumatic brain injury, dementia and post-stroke

Musculoskeletal injuries, including broken bones, disk herniations, and torn muscles and tendons

Any condition involving mitochondrial dysfunction

Any condition involving damaged microcirculation or that can benefit from capillary growth

Chronic infections such as Lyme disease, and subacute infections that cause damage over time

Cancer co-management — As noted by Sonners, researchers are looking at HBOT in cancer treatments in a number of different ways. For example, doing it may allow you to use less radiation or chemo and still get the same outcome. Or, it may allow the patient to tolerate higher amounts of radiation by speeding the healing between sessions. A third avenue of investigation is the use of HBOT in isolation.

HBOT is also showing promise for treating COVID-19 via a number of beneficial effects, including reversing hypoxia, reducing inflammation in the lungs, increasing viricidal reactive oxygen species, upregulating HIF-increasing host defense peptides and reducing proinflammatory cytokines such as IL-6.²⁰

Typically, hospitals will only provide HBOT if you have one of the 14 approved indications. If you’re interested in HBOT for other medical or longevity purposes, you’ll need to look into the private sector for treatment. The International Hyperbaric Association²¹ (IHA) and Hyperbaric Medical International²² (HMI) are two organizations that may direct you to more local centers.

You can also learn more on HBOTusa.com, which is Sonner's primary education website where you can find a list of treated conditions, research, the benefits of HBOT in athletics, testimonials and much more.

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I've previously discussed the synergy between magnesium and vitamin D, and the importance of vitamin D for optimal immune function and overall health — especially as it pertains to lowering your risk of COVID-19. Previous studies have also highlighted the role this duo plays in cognitive function among older adults, as well as overall mortality.

Vitamin D and Magnesium Protect Cognitive Health

One such study,¹ "Association of Vitamin D and Magnesium Status with Cognitive Function in Older Adults: Results from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2014," points out that vitamin D not only protects neuronal structures and plays a role in neuronal calcium regulation, but also appears to impact your risk for neurodegeneration as you grow older.

Magnesium, meanwhile, aside from being required for converting vitamin D to its active form,^2,3,4 also plays a role in cognitive health, and magnesium deficiency has been implicated in several neurological disorders.

Using NHANES data from 2,984 participants over the age of 60, the researchers compared serum vitamin D status and dietary magnesium intake against cognitive function scores.

After adjusting for confounding factors, including total calorie consumption and magnesium intake, higher blood levels of vitamin D positively correlated with decreased odds of having a low cognitive function score on the Digit Symbol Substitution Test.

The same trend was found when they looked at vitamin D intake, rather than blood level. The correlation of higher vitamin D levels and better cognitive function was particularly strong among those whose magnesium intake was equal to or greater than 375 mg per day. According to the authors:⁵

"We found that higher serum 25(OH)D levels were associated with reduced risk of low cognitive function in older adults, and this association appeared to be modified by the intake level of magnesium."

Magnesium Improves Brain Plasticity

While magnesium intake by itself did not appear to have an impact on cognitive function in the study above, other research has highlighted its role in healthy cognition.

Memory impairment occurs when the connections (synapses) between brain cells diminish. While many factors can come into play, magnesium is an important one. As noted by Dr. David Perlmutter, a neurologist and fellow of the American College of Nutrition:⁶

"It has now been discovered that magnesium is a critical player in the activation of nerve channels that are involved in synaptic plasticity. That means that magnesium is critical for the physiological events that are fundamental to the processes of learning and memory."

A specific form of magnesium called magnesium threonate was in 2010 found to enhance "learning abilities, working memory, and short- and long-term memory in rats."⁷ According to the authors, "Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions."

COVID-19 Can Deprive Brain of Oxygen

While we're on the topic of the brain, a July 1, 2020, article⁸ in The Washington Post reviewed findings from autopsies of COVID-19 patients. Surprisingly, Chinese researchers have reported⁹ that COVID-19 patients can exhibit a range of neurological manifestations.

A June 12, 2020, letter to the editor¹⁰ published in The New England Journal of Medicine also discusses the neuropathological features of COVID-19. As reported by The Washington Post:¹¹

"Patients have reported a host of neurological impairments, including reduced ability to smell or taste, altered mental status, stroke, seizures — even delirium … In June, researchers in France reported that 84% of patients in intensive care had neurological problems, and a third were confused or disoriented at discharge.

… Also this month, those in the United Kingdom found that 57 of 125 coronavirus patients with a new neurological or psychiatric diagnosis had experienced a stroke due to a blood clot in the brain, and 39 had an altered mental state.

Based on such data and anecdotal reports, Isaac Solomon, a neuropathologist at Brigham and Women's Hospital in Boston, set out to systematically investigate where the virus might be embedding itself in the brain.

He conducted autopsies of 18 consecutive deaths, taking slices of key areas: the cerebral cortex (the gray matter responsible for information processing), thalamus (modulates sensory inputs), basal ganglia (responsible for motor control) and others …"

Interestingly, while doctors and researchers initially suspected that brain inflammation was causing the neurological problems seen in some patients, Solomon's autopsies found very little inflammation. Instead, these neurological manifestations appear to be the result of brain damage caused by oxygen deprivation.

Signs of oxygen deprivation were present both in patients who had spent a significant amount of time in intensive care, and those who died suddenly after a short but severe bout of illness. I believe this is likely due to increases in clotting in the brain microvasculature.

Solomon told The Washington Post he was "very surprised," by the finding. It makes sense, though, considering COVID-19 patients have been found to be starved for oxygen. As reported by The Washington Post:¹²

"When the brain does not get enough oxygen, individual neurons die … To a certain extent, people's brains can compensate, but at some point, the damage is so extensive that different functions start to degrade … The findings underscore the importance of getting people on supplementary oxygen quickly to prevent irreversible damage."

Magnesium and Vitamin D Impact Mortality

Getting back to magnesium and vitamin D, previous research¹³ using NHANES data from 2001 through 2006 found the duo has a positive impact on overall mortality rates. This study also pointed out that magnesium "substantially reversed the resistance to vitamin D treatment in patients with magnesium-dependent vitamin-D-resistant rickets."

The researchers hypothesized that magnesium supplementation increases your vitamin D level by activating more of it, and that your mortality risk might therefore be lowered by increasing magnesium intake. That is indeed what they found. According to the authors:

"High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively. Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency.

Additionally, the inverse association between total magnesium intake and vitamin D insufficiency primarily appeared among populations at high risk of vitamin insufficiency.

Furthermore, the associations of serum 25(OH)D with mortality, particularly due to cardiovascular disease (CVD) and colorectal cancer, were modified by magnesium intake, and the inverse associations were primarily present among those with magnesium intake above the median.

Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status. The associations between serum 25(OH)D and risk of mortality may be modified by the intake level of magnesium."

Magnesium Lowers Vitamin D Requirement by 146%

According to a scientific review^14,15 published in 2018, as many as 50% of Americans taking vitamin D supplements may not get significant benefit as the vitamin D simply gets stored in its inactive form, and the reason for this is because they have insufficient magnesium levels.

Research published in 2013 also highlighted this issue, concluding that higher magnesium intake helps reduce your risk of vitamin D deficiency by activating more of it. As noted by the authors:¹⁶

"High intake of total, dietary or supplemental magnesium was independently associated with significantly reduced risks of vitamin D deficiency and insufficiency respectively.

Intake of magnesium significantly interacted with intake of vitamin D in relation to risk of both vitamin D deficiency and insufficiency … Our preliminary findings indicate it is possible that magnesium intake alone or its interaction with vitamin D intake may contribute to vitamin D status."

More recently, GrassrootsHealth concluded¹⁷ you need 146% more vitamin D to achieve a blood level of 40 ng/ml (100 nmol/L) if you do not take supplemental magnesium, compared to taking your vitamin D with at least 400 mg of magnesium per day.

The interplay between magnesium and vitamin D isn't a one-way street, though. It goes both ways. Interestingly, while vitamin D improves magnesium absorption,¹⁸ taking large doses of vitamin D can also deplete magnesium.¹⁹ Again, the reason for that is because magnesium is required in the conversion of vitamin D into its active form.

Magnesium + Vitamin K Lowers Vitamin D Requirement Even More

Magnesium isn't the only nutrient that can have a significant impact on your vitamin D status. GrassrootsHealth data further reveal you can lower your oral vitamin D requirement by a whopping 244% simply by adding magnesium and vitamin K2. As reported by GrassrootsHealth:²⁰

"… 244% more supplemental vitamin D was needed for 50% of the population to achieve 40 ng/ml (100 nmol/L) for those not taking supplemental magnesium or vitamin K2 compared to those who usually took both supplemental magnesium and vitamin K2."

How to Boost Your Magnesium Level

The recommended daily allowance for magnesium is around 310 mg to 420 mg per day depending on your age and sex,²¹ but many experts believe you may need anywhere from 600 mg to 900 mg per day.²²

Personally, I believe many may benefit from amounts as high as 1 to 2 grams (1,000 to 2,000 mg) of elemental magnesium per day, as most of us have EMF exposures that simply cannot be mitigated, and the extra magnesium may help lower the damage from that exposure.

My personal recommendation is that unless you have kidney disease and are on dialysis, continually increase your magnesium dose until you have loose stools and then cut it back. You want the highest dose you can tolerate and still have normal bowel movements.

When it comes to oral supplementation, my personal preference is magnesium threonate, as it appears to be the most efficient at penetrating cell membranes, including your mitochondria and blood-brain barrier. But I am also fond of magnesium malate, magnesium citrate, and ionic magnesium from molecular hydrogen as each tablet has 80 mg of elemental magnesium.

Eat More Magnesium-Rich Foods

Last but not least, while you may still need magnesium supplementation (due to denatured soils), it would certainly be wise to try to get as much magnesium from your diet as possible. Dark-green leafy vegetables lead the pack when it comes to magnesium content, and juicing your greens is an excellent way to boost your intake. Foods with high magnesium levels include:²³

Avocados	Swiss chard
Turnip greens	Beet greens
Herbs and spices such as coriander, chives, cumin seed, parsley, mustard seeds, fennel, basil and cloves	Broccoli
Brussel sprouts	Organic, raw grass fed yogurt and natto
Bok Choy	Romaine lettuce

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The older you get, the more important your muscle mass becomes. Not only are strong muscles a requirement for mobility, balance and the ability to live independently, but having reserve muscle mass will also increase your chances of survival¹ when sick or hospitalized.

Muscle is lost far more easily and quicker than it’s built, so finding ways to continuously promote and maintain your muscle mass is really crucial, especially as you get older.

Age-related loss of muscle mass is known as sarcopenia, and if you don’t do anything to stop it you can expect to lose about 15% of your muscle mass between your 30s and your 80s.² An estimated 10% to 25% of seniors under the age of 70 have sarcopenia and as many as half those over the age of 80 are impaired with it.³

In the lecture above, Brendan Egan, Ph.D., associate professor of sport and exercise physiology at the School of Health and Human Performance and the National Institute for Cellular Biotechnology at Dublin City University in Ireland, reviews the latest research on exercise training for aging adults, which places a significant focus on building and maintaining muscle, and the nutritional components that can help optimize training results.

Muscle Strength and Function in Relation to Muscle Size

While it’s true that larger muscle is indicative of stronger, more functional muscle, it’s not a true 1-to-1 relationship. As noted by Egan, “you can have situations where you can gain back function without necessarily gaining muscle size.” To illustrate this point, Egan presents data from the Baltimore Longitudinal Study of Aging, which looked at leg strength and lean muscle mass.

While declines in muscle mass and strength are relatively well-synchronized in the 35- to 40-year-old group, strength dramatically drops off as you get into the 75-year-old and over groups, with 85-year-olds seeing dramatic declines in strength and function relative to the decline in muscles size.

Speed as a Measure of Functional Muscle Capacity

One way to measure functional capacity in older adults is gait (walking) speed, which is a strong predictor of life expectancy. Data suggest that if you have a walking speed of 1.6 meters (about 5.2 feet) per second (approximately 3.5 mph) at the age of 65, your life expectancy is another 32 years, meaning you may live into your late 90s.

Having a walking speed at or below the cutoff for sarcopenia, which is 0.8 meters (about 2.6 feet) per second, your life expectancy would be another 15 years, which means you’d be predicted to live to 80. At this speed, you would not be able to make it safely across a typical pedestrian crossing before the light changes to red.

Strength as a Predictor of Survival

Strength can also tell us a lot about an individual’s chances of survival. Egan presents data from a study in which people’s chest and leg press strength were measured to arrive at a composite score of whole body strength. The pattern is quite revealing, showing the strongest one-third of the population over 60 had a 50% lower death rate than the weakest.

Exercise guidelines recommend getting 150 minutes of aerobics exercise and two strength training sessions per week. As noted by Egan, you need both. It’s not just one or the other.

Research shows aerobic exercise in isolation reduces your all-cause mortality by 16% and strength training-only reduces it by 21%, whereas if you do both, you reduce your all-cause mortality by 29%.⁴ Disturbingly, U.K. data suggest only 36.2% of adults over the age of 30 meet aerobic guidelines, and a minuscule 3.4% meet strength training guidelines.

Part of the problem may be that many don’t want to go to the gym. But there’s little difference between doing gym-based strength training and doing bodyweight resistance training at home.

The Danger of Bedrest and Disuse Atrophy

As noted by Egan, enforced bedrest, such as acute hospitalization, can have a dramatic impact on your muscle mass. For example, a 2015 review⁵ in Extreme Physiology & Medicine notes you can lose 2.5% of your muscle mass in the first two weeks of bedrest. By Day 23, you can have lost up to 10% of your quadriceps muscle mass. As explained in this review:⁶

“Skeletal muscle mass is regulated by a balance between MPS [muscle protein synthesis] and MPB [muscle protein breakdown]. In a 70-kg human, approximately 280 g of protein is synthesized and degraded each day.

The two processes are linked … as facilitative or adaptive processes, whereby MPS facilitates (allows modulation of muscle mass) and MPB adapts (limiting said modulation).

When exposed to an anabolic stimulus, MPS rises. MPB rises too, but to a lesser amount, resulting in a net synthetic balance. In response to an anti-anabolic stimulus, MPS decreases and MPB decreases to a lesser degree, resulting in a net breakdown.

The interaction between critical illness and bed rest may result in greater muscle loss compared to bed rest alone. The musculoskeletal system is a highly plastic and adaptive system, responding quickly to changing demands. Relatively short periods of immobilization decrease MPS, with no effect on MPB.

Furthermore, this altered balance is relatively resistant to high dose amino acid delivery … Immobilization has significant effects on peripheral muscle aerobic capacity, contractility, insulin resistance and architecture.

Microvascular dysfunction occurring in severe sepsis is associated with immobilization and may have an additive effect on reducing MPS. In critically ill patients, MPS is reduced even with nutritional delivery, with increased MPB seen, leading to a net catabolic state and thus muscle wasting.”

Research⁷ has shown even healthy young subjects in their 20s can lose 3.1 pounds of muscle mass in a single week of bedrest. This is why it is so important to have a reserve in case you wind up in the hospital and lose this much muscle mass. It may take you the better part of a year to regain that muscle, as gaining muscle mass is hard work and many elderly fail to do so.

The loss of muscle mass also significantly decreases your insulin sensitivity. One of the reasons for this has to do with the fact that muscle tissue is a significant reservoir for the disposal of glucose. Your muscle tissue also produces cytokines and anti-inflammatory myokines that play an important role in health.

Concurrent Exercise Training

While three to five sessions of aerobic exercise and two or more strength sessions per week may sound like a lot, for many, the lack of time is a restricting factor. However, some of these sessions can be done together. “That’s called concurrent exercise training,” Egan says.

He goes on to cite research looking at time matched concurrent exercise in the elderly, 65 and older, where an aerobic training group and a strength training group were compared to a group that spent half of their session doing aerobic exercise and the other half doing resistance training. All groups spent the same overall time exercising (30 minutes, three times a week for 12 weeks).

In terms of leg strength, the concurrent training group had better responses to training than aerobic or strength training alone. There was little difference in lean body mass, meaning they didn’t necessarily bulk up, but they had a 50% increase in strength nonetheless. They also lost more body fat around the trunk area. In short, concurrent training appears to give you more bang for your buck.

Blood Flow Restriction Training

One of the reasons I’m so passionate about blood flow restriction (BFR) training is because it has the ability to prevent and widely treat sarcopenia like no other type of training.

There are several reasons why BFR is far superior to conventional types of resistance training in the elderly. Importantly, it allows you to use very light weights, which makes it suitable for the elderly and those who are already frail or recovering from an injury. And, since you’re using very light weights, you don’t damage the muscle and therefore don’t need to recover as long.

While most elderly cannot engage in high-intensity exercise or heavy weightlifting, even extraordinarily fit individuals in their 60s, 70s and 80s who can do conventional training will be limited in terms of the benefits they can achieve, thanks to decreased microcirculation. This is because your microcirculation tends to decrease with age.

With age, your capillary growth diminishes, and capillary blood flow is essential to supply blood to your muscle stem cells, specifically the fast twitch Type II muscle fiber stem cells. If they don’t have enough blood flow — even though they’re getting the signal from the conventional strength training — they’re not going to grow and you’re not going to get muscle hypertrophy and strength.

BFR, because of the local hypoxia that is created, stimulates hypoxia-inducible factor-1 alpha (HIF1a) and, secondarily, vascular endothelial growth factor (VEGF), which acts as “fertilizer” for your blood vessels. VEGF allows your stem cells to function the way they were designed to when they were younger.

What’s more, the hypoxia also triggers vascular endothelial growth factor, which enhances the capillarization of the muscle and likely the veins in the arteries as well. Building muscle and improving blood vessel function are related, which is why BFR offers such powerful stimulus for reversing sarcopenia.

In short, BFR has a systemic or crossover training effect. While you’re only restricting blood flow to your extremities, once you release the bands, the metabolic variables created by the hypoxia flow into your blood — lactate and VEGF being two of them — thereby spreading this “metabolic magic” throughout your entire system. To learn more, please see my special report, “What You Need to Know About BFR,” and “BFR Training for Muscle Mass Maintenance.”

Nutrition for Muscle Maintenance

It should come as no surprise that there is an important synergy between nutrition and exercise. When it comes to muscle building and maintenance, amino acids, the building blocks of protein, are of particular importance.

In the podcast above, Megan Hall, scientific director at Nourish Balance Thrive delves into this topic at greater depth and reviews the current recommended daily allowances of protein compared to the optimal levels needed to support muscle mass and strength in at various life stages.⁸

Research⁹ looking at post-prandial protein handling and amino acid absorption shows 55.3% of the dietary protein of a given meal is in circulation within five hours after eating, which significantly increases muscle protein synthesis.

Research¹⁰ suggests healthy young adult men “max out the protein synthesis signal from a given meal” at a dose of 0.24 grams of protein per kilogram of total bodyweight, or 0.25 grams of protein per kilogram of lean body mass.

The current U.S.-Canadian recommended dietary protein allowance is 0.8 g/kg/d (0,36/grams/pound/day), but healthy older adults may actually require about 1.20 g/kg/d or .55 grams/pound/day. According to this study:¹¹

“Our data suggest that healthy older men are less sensitive to low protein intakes and require a greater relative protein intake, in a single meal, than young men to maximally stimulate postprandial rates of MPS [myofibrillar protein synthesis].

These results should be considered when developing nutritional solutions to maximize MPS for the maintenance or enhancement of muscle mass with advancing age.”

Amino acids also act as signaling molecules that trigger muscle growth. Leucine is a particularly potent signaling agent, although all of the amino acids are required to actually build the muscle. The richest source of leucine (which helps regulate the turnover of protein in your muscle), by far, is whey protein. In fact, it can be difficult to obtain sufficient amounts of leucine from other sources.

The typical requirement for leucine to maintain body protein is 1 to 3 grams daily. However, to optimize its anabolic pathway, research shows¹² you need somewhere between 8 and 16 grams of leucine per day, in divided doses.^13,14

To reach the 8-gram minimum, you’d have to eat nearly 15 eggs.¹⁵ Whey, on the other hand, contains about 10% leucine (10 grams of leucine per 100 grams of protein).¹⁶ So, 80 grams of whey protein will give you 8 grams of leucine.

Time-Restricted Eating Adds Benefits

One of the problems with Egan is that he’s not very literate on time-restricted eating. During the question and answer portion, an audience member asks him about it and he admits he hasn’t studied it.

This is important because restricting your eating window to six to eight hours, which means you’re fasting 14 to 18 hours each day, would make it far easier for each of the meals to be over the leucine threshold. It will also activate autophagy, which is another factor essential for optimal muscle growth.

Autophagy is a self-cleaning process in which your body digests damaged cells, which in turn encourages the proliferation of new, healthy cells. The harder your workout, the more autophagy you will activate.

So, I recommend fasting for as long as you can before your morning workout, and then, shortly thereafter, have your largest meal of the day with plenty of high-quality protein, making sure you get several grams of leucine and arginine, both of which are potent mTOR stimulators.

The mTOR pathway is an important key for protein synthesis and muscle building. As explained in David Sabatini’s excellent review paper “mTOR at the Nexus of Nutrition, Growth, Ageing and Disease,” published in Nature Reviews Molecular Cell Biology:¹⁷

“Over the past two and a half decades, mapping of the mTOR signaling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy.

Given the pathway’s central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signaling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing.”

In summary, fasting activates autophagy, allowing your body to clean out damaged subcellular parts. Exercising while fasted maximizes autophagy even further. In fact, exercising while you are fasting for more than 14 to 18 hours likely activates as much autophagy as if you were fasting for two to three days. It does this by increasing AMPK, increasing NAD+ and inhibiting mTOR.

Refeeding with protein after your fasted workout then activates mTOR, thus shutting down autophagy and starting the rebuilding process. These two processes need to be cyclically activated to optimize your health and avoid problems.

Muscle Health Is Central to an Active Lifestyle

As noted by Egan, “Hopefully I've convinced you that muscle health is central to active lifestyles. There's been this increased awareness of muscle size, but I think we need to emphasize the idea about strength and function. These are the things that are easiest to change with the right type of training.”

In short, if you want to increase muscle size and strength, then there’s no getting around resistance training. It simply must be part of your exercise prescription, and concurrent training, where you’re combining aerobic and strength training in a given session is a time-efficient model.

BFR is also a particularly excellent way to ensure you’re getting effective strength training without the risks of conventional strength training using heavy weights, and is easy to combine with exercises such as walking and swimming. You simply wear the BFR bands while walking or exercising as normal.

Defy Aging by Improving Your Muscle Mass

In my February 2020 interview with Ben Greenfield, author of “Boundless: Upgrade Your Brain, Optimize Your Body & Defy Aging,” we discuss the importance of strength training and getting the appropriate amount of protein to build and maintain your muscle mass and optimize mitochondrial density and biogenesis.

In summary, Greenfield recommends a fitness program that includes the following types of exercise in order to target the main pathways involved in health and aging:

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Youthfulness, vitality and a long, prosperous life have been sought after throughout human history. And now, it seems scientists may have discovered one of the keys to turning back the hands of time.

Researchers from Arizona State University and Texas A&M University have made a breakthrough discovery in plant DNA that could lead to stopping cancer cold and slowing the aging process, ABC affiliate News 15 Arizona reports.¹

The research involves telomerase, an enzyme that produces the DNA of telomeres, which have been shown to play a role in the aging process. As your telomeres lengthen, they protect your cells from aging.

Take It From the Experts: Centenarians Share Their Secrets

While direct applications from the study to human health are distant, there are a number of things you can do now to improve your health span, according to one of the co-authors. In interviews and surveys with centenarians, certain themes came up time and time again when they explained why they've lived so long. The 10 most common reasons they gave for their long lives were:

Keeping a positive attitude	Eating good food
Participating in moderate exercise like walking, gardening swimming, etc.	Living clean (not smoking or drinking excessively)
Living independently	Having family to interact with
Having a circle of friends	Being born with "good" genes
Having faith/spirituality	Staying mentally active and continually learning

Centenarians are the fastest growing segment of the U.S population, with numbers doubling every decade; by the year 2050, the number of people who will have reached the century mark is expected to pass 1 million.

Centenarians have 60% lower rates of heart disease, stroke and high blood pressure, yet scientific explanations for their health and longevity remain elusive. As a group, they are happy and optimistic and have extremely low rates of depression and other psychiatric problems, suggesting you may live longer by maintaining the right attitude.

Hopefulness and Positivity Affect the Heart

There are compelling links between cardiac health and mental health. For example, having untreated depression or anxiety disorder increases your odds of having a heart attack or developing heart disease. Stress hormones are again a primary culprit.

According to Julia Boehm, author of earlier Harvard studies looking at optimism and cardiovascular disease (CVD):²

"The absence of the negative is not the same thing as the presence of the positive. We found that factors such as optimism, life satisfaction and happiness are associated with reduced risk of CVD regardless of such factors as a person's age, socioeconomic status, smoking status or body weight."

With a later study,³ author Eric Kim told The Harvard Gazette:

"While most medical and public health efforts today focus on reducing risk factors for diseases, evidence has been mounting that enhancing psychological resilience may also make a difference.

Our new findings suggest that we should make efforts to boost optimism, which has been shown to be associated with healthier behaviors and healthier ways of coping with life challenges."

The Significance of Sound Sleep

Getting adequate sleep is an important part of both mental and physical health. Too much or too little can lead to metabolic issues, as well as changes in mood and your ability to focus. Your circadian rhythm, which affects your sleep/wake cycle, holds implications for your brain, body temperature, hormones and cell regeneration among other things.⁴

"Irregular rhythms have been linked to various chronic health conditions, such as sleep disorders, obesity, diabetes, depression, bipolar disorder and seasonal affective disorder," say scientists from the National Institute of General Medical Sciences.⁵

Italian researchers found that deletion of a specific gene related to aging also affects glucose homeostasis. According to their article, published in the journal Glia, "Disruption of the circadian cycle is strongly associated with metabolic imbalance and reduced longevity in humans."⁶

Telomeres and telomerase activity are also controlled by your circadian rhythm,⁷ making proper sleep an important part of longevity. In a 2007 study involving 21,268 adult twins, Finnish researchers found that adults who slept more than eight hours per night, or less than seven, showed increased risk of death.⁸

Of course, the quality of your sleep is also important, not just the quantity. Good quality sleep, in the appropriate amount, can improve how you think and adapt to the demands on your time and changes throughout your day. There is evidence suggesting that a calm mind and active body are two important ingredients for longevity.

The meditative technique known as "mindfulness" has even been shown to have a beneficial effect on genetic expression. According to a 2018 article in Brain, Behavior, and Immunity,⁹ meditation has also been found to affect the enzyme telomerase, which some researchers believe is actively involved with the process of aging.

After Resting, Be Sure to Refuel

Additionally, there are many other strategies you can implement to improve your health and extend your life span. To live longer, you need to counteract the progressive loss of muscle mass by increasing your protein intake as you age. The elderly, bodybuilders and endurance athletes typically have higher than normal protein requirements for their age group.

It's also important to cycle high and low protein intake. Ideally, combine protein restriction with time-restricted eating, followed by increased protein intake on strength training days.

Fasting 16 to 20 hours each day is likely ideal, as this allows your body to more thoroughly deplete the glycogen stores in your liver. Benefits of fasting include the suppression of mammalian target of rapamycin (mTOR) and the activation of autophagy, both of which play decisive roles in disease prevention and longevity.

You'd also be wise to avoid eating two to three hours before bed, as late-night eating will decrease your nicotinamide adenine dinucleotide (NAD+) level, which is crucial for health and longevity. Late-night eating will also make you pack on unwanted pounds, as the excess calories will not be burned but stored as fat.

Preventing Cognitive Decline

Naturally, if you're going to live longer, you'll want to be healthy for the remainder, and that includes maintaining your cognitive function. Specific nutrients that can help prevent dementia and cognitive decline include vitamin D, DHA, folate and magnesium. Additional nutrients of notable interest, which are readily available in supplement form, include:

• Astaxanthin — Commonly called "king of the carotenoids," is a potent anti-inflammatory from specific types of microalgae and may be useful for treating joint and muscle pain. It also supports healthy vision and can be used as an "internal sunscreen."
• Ergothioneine — Found in porcini mushrooms, ergothioneine appears to play a specific role in protecting your DNA from oxidative damage. Along with glutathione, it may offer protection against age-related conditions such as Alzheimer's disease, cancer and heart disease.
• PQQ — Particularly important for the health and protection of your mitochondria, PQQ has been shown to help protect against Alzheimer's and Parkinson's disease. It also works synergistically with CoQ10, producing better results than when either one is used alone. Celery, parsley and kiwi are dietary sources of PQQ.

Kick the Chemicals to the Curb

Naturally, there's also the issue of toxic exposures, which can take a toll on your health, so avoiding toxins is a given, right along with eating a wholesome diet of organic, unprocessed foods.

This includes tossing out your toxic household cleaners, soaps, personal hygiene products, air fresheners, bug sprays, lawn pesticides and insecticides, just to name a few, and replacing them with nontoxic alternatives.

A group of scientists from Southeast University and Changzhou No. 7 People's Hospital in China recently published a study¹⁰ about the role of plastics in our environment and how long-term exposure affects our health. They found that high concentrations of nanoplastic particles reduced the life span of roundworms.

They believe that different levels of exposure may have effects on locomotion and immune response, indicating that nanopolystyrene is likely toxic to all types of organisms.

"Our results highlight the potential of long-term nanopolystyrene exposure in reducing longevity and in affecting health state during the aging process in environmental organisms," they wrote. Next week I will post my interview with leading researcher James Clement on his book, "The Switch," that will go into far more fascinating details on this topic.

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The fabled "fountain of youth" wasn't just an intriguing physical location sought after by ancient explorers, but a concept that has captured the imaginations of ordinary mortals since the dawn of time. Some have pursued every avenue they could think of to help them live longer.

But like so many things in life, scientists found that a little healthy competition is all that's needed — cell competition, that is. Scientists in Japan recently discovered a protein called COL17A1 that encourages cell competition by driving out weak cells and revitalizing stronger cells toward replication and, in the process, maintaining tissue fitness.

Aging and other stressors, such as excess ultraviolet radiation and damaging free radicals, take a toll on your skin, and so does steadily depleting COL17A1, as it replicates weaker cells, not stronger ones. The inevitable results: skin that is thinner, more prone to damage and takes longer to heal.

The research involved the use of mice tails because of their similarity to human skin.¹ Emi Nishimura, a professor at the Tokyo Medical and Dental University's stem cell biology department and leader of the featured study, noted that "Damaged or stressed stem cells can be selectively eliminated by intact stem cells every day in our skin."

How COL17A1 'Rescues' Aging Skin

When the researchers learned how important COL17A1 is in maintaining skin resilience, they set about investigating the possibility of stimulating it once it was depleted. They looked for compounds with the ability to "kick-start" the antiaging process and identified two chemical compounds: Both Y27632 and apocynin proved to produce positive results on skin cells, pointing to ways of "facilitating skin regeneration and reducing skin aging." 

The two compounds "significantly promoted" repair and regeneration even to deep-tissue skin wounds, and it was done two ways, according to the study, published in the journal Nature.² As the study authors observed:

"Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing.

Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention."³

How Y27632 and Apocynin 'Kick-Start' Antiaging

When two professors from the University of Colorado reviewed the Tokyo study, they reported that fruit flies had been the only subjects ever closely scrutinized in regard to cell competition.

Ganna Bilousova and James DeGregori wrote that the research conducted by Nishimura and her colleagues could be considered "proof of principle" in regard to the ability of Y27632 and apocynin to fight aging. They also noted that the research "Provides evidence that healthy cells in mammals can also efficiently repopulate adult tissues, replacing unfit or damaged cells."⁴

While conceding that more studies would be required to nail down the mechanisms responsible for cell competition in other tissues, Nishimura told news agency AFP⁵ they also hoped to identify compounds capable of performing the same antiaging functions in other organs.

She added, "We are working on other epithelial organs as well to find out (whether) similar competition may underlie long-term tissue maintenance as well as organ ageing."⁶

She also noted the study team's hope that the research would lead to the development of tablets, creams and other products that could halt the deterioration of and promote the repair of skin cells, and that they could "collaborate with pharmaceutical or cosmetic companies for the clinical use of the chemicals."⁷ According to a Mediators of Inflammation study published in 2008:

"Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH-oxidase. It can decrease the production of superoxide from activated neutrophils and macrophages while the ability of phagocytosis remains unaffected."⁸

In explanation, neutrophils are the most common type of white blood cells that help your body respond to infection and heal damaged tissue.⁹ Macrophages "act as antimicrobial warriors" that "play critical roles in immune regulation and wound healing."¹⁰ Phagocytosis is described as a complex process for the ingestion and elimination of pathogens, and fundamental for tissue homeostasis.¹¹

Apocynin: What It Is and What It Does

Perhaps a simpler way of characterizing apocynin is to explore where it's found. The 2008 inflammation study¹² notes that it was first described in an investigation conducted in 1883 when the compound was isolated from the roots of Canadian hemp (Apocynum cannabinum) and used to treat dropsy and heart problems.

It was also found in the root of Picrorhiza kurroa, a plant with the faint odor of vanilla, native to India, Nepal, Tibet and Pakistan and common in Ayurvedic treatments. In India and Sri Lanka, extracts were used "for the treatment of ailments of liver, heart, joints, and lungs."¹³

A 2014 study¹⁴ shows that the "small phenolic antioxidant" known as apocynin and extracted from the Jatropha multifida plant, also known as Guatemala rhubarb or coral plant, grown from Mexico to Central America to Brazil, was shown to have potential for treating neurodegenerative diseases.

Researchers also found apocynin to be one of five volatile vanilla flavor compounds in the vanilla bean, aka Vanilla planifolia.¹⁵ Another study suggested its cancer-fighting potential:

"The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model … (and) their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells."¹⁶

Besides its advantageous effects on fighting inflammation and free radical scavenging, apocynin has a history of successful treatment of a long list of ailments, including:

• Ischemia-reperfusion, characterized by damaged lung tissue due to a lack of oxygen and subsequent returned supply,¹⁷ with apocynin also showing potential in treating several other respiratory diseases
• Possible neuroprotective abilities, particularly in brain injury following an eschemic stroke,¹⁸ as well as reduced cerebral and vascular injury in experimental stroke models¹⁹
• Potential in the treatment of atherosclerosis due to reduced blood pressure,²⁰ and preventing endothelial dysfunction²¹
• Chronic inflammatory joint diseases such as osteoarthritis and rheumatoid arthritis²²
• Inhibiting tumor migration in breast cancer cells²³

A 2014 study notes that "the perspectives for apocynin in chronic neurodegenerative disorders," suggests a "potentially beneficial role" in amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease,²⁴ Alzheimer's²⁵ and Parkinson's disease.²⁶ Although mouse models were the usual subjects in experimentation, the researchers are hopeful that apocynin will prove just as effective in human patients.

Other Beneficial Functions of Apocynin

Arguably the most important aspect of apocynin is its role in fighting inflammation, and the above study notes that it's been demonstrated in a variety of cell and animal models. Apocynin also "inhibits the assembly of NADPH-oxidase that is responsible for reactive oxygen species (ROS) production."²⁷

The 2008 study explains NADPH-oxidase as the enzyme responsible for ROS production, so suppressing it is often the goal in disease prevention therapies. When antioxidants are in place or introduced, oxidative stress is diminished. Your body produces an "armory of antioxidants to defend itself," which nonetheless are sometimes insufficient to effectively defend against ROS.

ROS damages your cells as well as your DNA, which is part of the reason your body begins showing signs of aging. To a large degree, how well your mitochondria work is determined by your diet, optimally a ketogenic diet (in which you replace carbs with moderate amounts of high-quality protein and high amounts of beneficial fat).

However, the featured study notes that it's the excessive production of ROS that becomes damaging, and that's how it's been implicated in the progression of many diseases. It's also why apocynin is noted as a potential treatment for many of them.

A Mediators of Inflammation review concluded that apocynin, besides its lack of known side effects, deserves further attention in the development of "safe and selective anti-inflammatory drugs which lack the often serious side effects of steroids."²⁸

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Aside from being vital pollinators, bees produce a number of products that benefit human health. Honey¹ is an obvious one, but there are others as well, such as royal jelly, a nutritious substance secreted by nurse bees as exclusive nourishment for the queen of the hive.

Recent research^2,3,4,5 by Stanford University scientists found royalactin (also known as major royal jelly protein 1, or MRJP1), a protein found in royal jelly responsible for the queen's massive growth, has the ability to keep embryonic stem cells pluripotent.

This initial finding could eventually lead to the development of drugs to boost stem cells in the human body, allowing for the regeneration of healthy tissue in damaged organs, be it your heart, eyes, skin or spinal cord.

They also identified a protein with similar qualities found in mammals, which they dubbed Regina — a nod to the queen bee for which royalactin is made — which like royalactin allows embryonic stem cells to maintain their naïve state. According to the authors:

"This reveals an important innate program for stem cell self-renewal with broad implications in understanding the molecular regulation of stem cell fate across species."

Researchers Discover Innate Program for Stem Cell Self-Renewal

Embryonic stem cells are the product of the initial meeting of egg and sperm. Three days after fertilization of the egg, an inner cell mass can be isolated, and these are the embryonic stem cells that, if left alone, will grow into a fetus.

Stem cells are pluripotential, meaning that they have the ability to turn into any and every type of tissue to form an entire being, be it animal or human. Adult stem cells, in contrast, are multipotential, meaning they only have the ability to form subsets of tissue.

The problem researchers have is that embryonic stem cells have a tendency to differentiate into mature tissue cells of various kinds when grown in the lab, and in order to use the stem cells for research and/or therapies, they must be kept in their "naïve" state long enough. As explained by New Atlas:⁶

"With the ability to differentiate into all kinds of cells that serve specialized functions, like muscle cells, red blood cells or brain cells, embryonic stem cells have incredible potential. But growing them in the laboratory is difficult, because their natural inclination is to quickly outgrow their pluripotent state and become something else.

To preserve that pluripotency, scientists must add special molecules to the culture that inhibit that behavior. Wang and his team found that by adding royalactin instead, they could stop the embryonic stem cells from differentiating just as well.

In fact, they found that they were able to maintain the cells in their embryonic state for up to 20 generations in culture without the need for inhibitors."

This was a complete surprise. Normally, scientists must use leukemia inhibitor factor to prevent the embryonic stem cells from differentiating when grown in culture. What they discovered is that royalactin performed the same function. The question is: How?

Royalactin-Like Protein in Mammals Inhibit Embryonic Stem Cell Differentiation

Mammals do not produce the royalactin protein, yet the royalactin activated a network of genes known to code proteins that allow the embryonic stem cells to maintain their pluripotency. To find the answer, the researchers searched scientific databases to identify human proteins with structures similar to that of royalactin.

What they found was a protein known as NHL repeat-containing-3 protein or NHLRC3, produced during the development of the mammalian (including human) embryo. They then duplicated the mouse experiment using NHLRC3, which was found to trigger a similar gene network as royalactin.

The end result was the same — the embryonic stem cells maintained their pluripotency in culture. Kevin Wang, assistant professor of dermatology and lead author of the study, commented on the results, saying:⁷

"It's fascinating. Our experiments imply Regina is an important molecule governing pluripotency and the production of progenitor cells that give rise to the tissues of the embryo. We've connected something mythical to something real."

Next, Wang and his team will investigate whether Regina — the mammalian equivalent of royalactin — has the ability to affect cell regeneration and wound healing in adult animals. And, as reported by New Atlas:⁸

"It could be used as another way to keep embryonic stem cells pluripotent in the lab, and could one day lead to the development of synthetic versions that deliver stocks of stem cells in the human body.

[T]hose kinds of drugs could be used for all kinds of things, from generating healthy tissue for damaged hearts, degenerating eyes, injured spinal cords and severe burns."

What Is Royal Jelly and How Is It Made?

Royal jelly is a gelatinous, milky substance secreted by the hypopharyngeal and mandibular glands of worker honeybees between the sixth and twelfth days of their life,⁹ and is an essential food for the development of the queen bee. It's a complex substance containing proteins (12 to 15 percent), sugars (10 to 12 percent), fat lipids (3 to 7 percent), along with a variety of amino acids, vitamins and minerals.¹⁰

Compared with the short-lived and infertile worker bees, the queen bee, which is exclusively fed royal jelly, is characterized by her extended lifespan and her well-developed gonads. Therefore, royal jelly has been long-used as a supplement for nutrition, antiaging or infertility.

The larva selected to become queen is fed royal jelly exclusively, while the rest of the larva receive royal jelly along with pollen and honey. Research^11,12 reveals this exclusive royal jelly diet activates certain genes in the queen bee, allowing her to grow much larger and become such a prolific egg layer. The honey and beebread fed to worker bee larvae contains p-coumaric acid, and it's the presence or absence of p-coumaric acid that determines the caste of the bee.

Larvae fed royal jelly to which p-coumaric acid had been added produced adults with reduced ovary development. "Thus, consuming royal jelly exclusively not only enriches the diet of the queen-destined larvae, but also may protect them from inhibitory effects of phytochemicals present in the honey and beebread fed to worker-destined larvae," the researchers explain.¹³

Health Benefits of Royal Jelly

Folklore in Europe and Asia has it that royal jelly is a powerful rejuvenator capable of boosting longevity and fertility. It's also been used to promote hair growth and minimize wrinkles. In Chinese medicine, royal jelly is revered as a substance that helps increase life expectancy, prevent disease and restore youth.

The fact that the protein Regina in mammals and humans appears to work like royalactin in royal jelly could possibly account for some of these benefits. Royal jelly also has antimicrobial benefits, courtesy of bee defensin-1, an antimicrobial peptide found in it. Because of components such as these, it's fair to assume that royal jelly is in fact beneficial for humans.

That said, the idea that consuming royal jelly might somehow affect your stem cells is probably taking things too far. There's no evidence of that — only that royalactin allows mammalian embryonic stem cells in an undifferentiated state in a lab environment.

Also keep in mind that it's difficult to ensure potency and quality of royal jelly products on the market. Toxicology tests suggest most if not all honeys, for example, are tainted with the herbicide glyphosate, and the bee population has taken a hit around the world due to various pesticide exposures. If the bees have toxins in them, it's feasible their royal jelly might be contaminated as well.

Still, the research was conducted by a very prestigious institution and published in a respectable journal, and they seem to believe there are possibilities here. Just realize that the focus is on Regina, the mammalian protein equivalent of royalactin, and not on royal jelly itself.

Health Benefits of Bee Propolis

Propolis is yet another bee product with health benefits, including immune-boosting properties and strengthening your body's defenses against bacteria, viruses and other disease-causing organisms.

Propolis is used by bees to close openings in their beehives, which is why it is also referred to as "bee glue." The materials are usually taken from leaves, bark, flower buds and other plant parts. These are then combined with bee saliva, wax and pollen, which are then adhered to the hive holes.

Studies suggest propolis also protects the bees from bacterial infections and possible external elements that may endanger the whole colony. In some cases, propolis may also be used to encase the carcasses of hive intruders to stop bacteria from spreading.¹⁴

Propolis has been used for years in folk medicine because of its proposed effect on various body systems, dating back to the time of the ancient Greeks, Romans and Egyptians.

In fact, Hippocrates notes that propolis is beneficial for promoting wound healing, both internal and external, while Pliny the Elder documents that propolis may be used to treat tumors, muscle pain and ulcers. This bee product was also documented in the Persian manuscripts as a remedy for various conditions, including eczema and rheumatism.¹⁵

Today, propolis is used in a wide variety of skin care products, including creams and extracts to promote wound healing and ease various types of infections. It is also available as a supplement, with people taking it on a regular basis to boost their immune system function.¹⁶

Another Bee Product, Propolis Has Flavonol With Health Benefits

Research also suggests a flavanol in propolis called galangin has anticancer effects on several cancers, including melanoma, hepatoma, leukemia and colon cancer.

In one such study,¹⁷ galangin was found to induce apoptosis (programmed cell death) in two types of colon cancer cells (HCT-15 and HT-29 specifically), and that the effect killed the cancer cells in a dose-dependent manner. According to the authors:

"We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis.

In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer."

Galangin has also been shown to inhibit inflammation by regulating the nuclear factor-kappa B (NF-κB), PI3K/Akt and peroxisome proliferator activated receptor-γ (PPAR γ) signaling in activated microglia in the brain and thus should improve or prevent Alzheimer's.¹⁸ Additionally, galangin reduces insulin resistance by increasing the activity of hexokinase and pyruvate kinase, promoting glucose consumption and glycogen synthesis.¹⁹

Royal Jelly May Be Beneficial for Health, But Don't Expect Miracles

In summary, while royal jelly has a number of health benefits, it's premature to assume it can affect your stem cells directly. A number of studies done on royal jelly have focused on its potential effects on cancer, fertility and its role in testosterone production.

In one study,²⁰ infertile men were given different dosages of royal jelly and honey to increase the production of testosterone. After three months, those given royal jelly had higher testosterone levels, improved sperm active motility and luteinizing hormone levels, thus showing the potential impact royal jelly can have on infertility in men.

In another study,²¹ royal jelly was found to reduce symptoms of mucositis in patients suffering from neck and head cancer. Mucositis refers to the inflammation of the digestive tract brought on by chemotherapy and radiotherapy. Patients who were given royal jelly thrice a day showed a decreased occurrence of mucositis.

A recent study²² published in an obscure Chinese journal also suggests royal jelly has an antisenescence effect on human lung fibroblasts in cell cultures. Other studies have found royal jelly supplementation can improve menopausal symptoms²³ and Type 2 diabetes outcomes.^24,25

How to Identify a Quality Product

So, provided you can find a high-quality product (which can be expensive), it could be a valuable supplement in some instances. In terms of what to look for when shopping for a royal jelly product, here are a few pointers:

• Fresh royal jelly is ideal if you can find it, but lyophilized royal jelly is also a good and more convenient option
  
• To assess quality, look for 10-hydroxydecanoic acid (10-HDA) content. Most companies that care about quality will test their royal jelly for this. For fresh royal jelly the typical range is ~1.5 to 2.3 percent. For lyophilized royal jelly, it is ~4.5 to 6.6 percent
  
• Look for organic royal jelly as it is less likely to contain antibiotics or be adulterated

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