Chapter 4.: Dietary and Medical Interventions for Life Extension

 Protecting telomere erosion promotes:
1. Health; 2. Prevents diseases; and, Prevents premature aging. 1.
Water is the basic and most vital nutrient .2.
As water purity increases, the factors responsible for "Aging at the Molecular and Cellular" levels are proportionately ameliorated.
The factors involved in life extension, telomerase activity, and telomere shortening and water quality are complex.
Water serves as the body's transportation system, removes wastes and toxins, affects the digestive system, participates the the body's
biochemical reactions and 99% of all of the body's chemical reactions. 3.
As stated before, pure clean water is the fundamental dietary and medical intervention for telomere health and life extension.
Water purification, over and above the purity of water coming out of the tap, is fundamental to diminishing the shortening of
telomeres over time.
This mandates the use of water filters or other means to increase the purity of water coming out of the water faucet.
The expense of the same varies considerably based upon the degree of the increase in water purity gained.
However, simple water filters which increase the purity of water by decreasing  environmental and other pollutants are extremely economical.
The utilization of the "reverse osmosis" form of water purification is both more effective and more expensive.
As water purity increases, the effectiveness and efficiency of enzymatic and other biochemical reactions in the body increase improving the efficiency
of the essential basic biochemical pathways in the human body.
As stated before,"Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by the addition of the telomere repeat TTAGGG.." 4..
Chapter 2 delineates "Aging at the Molecular and Cellular Levels".
As per Chapter 2 and the aforementioned, aging at the molecular and cellular levels increases as water quality decreases.
Given the aforementioned, telomerase activity more efficiently and effectively reduces telomere shortening in direct proportion to the purity of water.
The amino acid,Beta- Alanine, plays a prominent role in telomerase activation through it's role in the biosynthesis of the dipeptide, Carnosine, and the peptide, epithalon., both of which are telomerase activators.. 5,6.
L-Carnosine is a dipeptide of the amino acids histidine and beta-alanine. 7.
The enzyme, Carnosine synthase, is the enzyme which catalyzes the reversible reaction of ATP + Beta-Alanine + L- Histidine= Carnosine + phosphate+ADP. 8.
Epithalon is a tetrapeptide made from four amino acids: alanine, glutamic acid, aspartic acid, and glycine. 9.
"The rate-limiting factor of carnosine synthesis is beta-alanine availability." 10.
 
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"The Beta-Alanine-Carnosine connection. We can increase our carnosine levels by increasing the ingestion of Beta-Alanine which is one of the two amino acids that make up carnosine.
Why not just take straight carnosine? When you ingest carnosine in isolation, most of it is broken down in the gastrointestinal (GI) tract into its constituent amino acids, beta-alanine and histidine. Some intact carnosine does escape the GI tract freely but even that amount is quickly broken down in our blood by the enzyme Carnosinase. In a very short time, all the carnosine you just ingested is either eliminated or converted to beta-alanine and histidine. These two amino acids are then taken into the muscle, where they are converted back to carnosine. This is the key. Unfortunately, only approximately 40% of the carnosine you take actually contains beta-alanine, making it inefficient at best .You are better off, from both efficiency and a financial standpoint, taking Beta-Alanine directly. You would have to take substantially more carnosine just to approach the increased levels of intramuscular carnosine achieved by taking the research supported dose of beta-alanine alone.

Here is why it is so important to use Beta-Alanine in supplement form to concentrate carnosine in your muscles. When you ingest Beta-Alanine, your body transports it into your muscles and with the help of the enzyme carnosine synthetase, combines it with histidine to rebuild carnosine within your muscles." 11.

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Given the aforementioned, L-Alanine oral ingestion should proportionately increase the absolute and relative amounts of both carnosine and epithalon, both of which are telomerase activators.

What is the human internal enzymatic reaction through which L-Alanine is created?
Alanine aminotransferase (ALAT) is that enzyme. It is, also, called Alanine transaminase (ALT).
It catalyzes the enzymatic reaction: L-glutamate + pyruvate = alpha-ketoglutarate + L-alanine. 12.
This is a reversible transamination reaction. 13.
"ALT (and all aminotransferases ) require the coenzyme pyridoxal phosphate , which is converted into pyridoxamine in the first phase of the reaction, when an amino acid is converted into a keto acid." 14.
Pyridoxal phosphate, the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. 15.
It is interesting to note that both L-Alanine and and lactate have the same molecular weight and number of valence electrons in their natural biological state.
This implies that a minimal error in ALA might result in the enzyme mistaking lactate for L-alanine resulting in an acceleration of the aging process because of the significant reduction of L-Alanine which would result.
The reference ranges for ALT are less than or equal to 34 IU/L for females and less than or equal to 52 IU/L for males. 16.
"In animals, L-lactate is constantly produced from  pyruvate via the  enzyme  lactate dehydrogenase (LDH) in a process of  fermentation during normal  metabolism and  exercise."17.

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"As you age, your risk of developing vitamin B6 deficiency increases. There are two reasons for that. First, older people generally consume less protein, which is the richest source of vitamin B6 , so their diets are more likely to be low in it. Second,many older adults metabolize the vitamin more rapidly than they did when they were younger, increasing the need for it on a daily basis. Signs of severe vitamin B6 deficiency include skin problems, anemia, depression, confusion, and convulsions." 18.

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Vitamin supplementation with vitamin B6 is appropriate, especially for older adults, given the aforementioned.

"Alanine aminotransferase increase is found among people who take Niacin, especially for people who are male, 60+ old, have been taking the drug < 1 month, also take medication Aspirin, and have high blood cholesterol." 19.
"Many anti-aging clinics are now using a range of supplements shown to activate the telomerase enzyme to help prevent the aging process and thus age related illness by preventing telomeres from shortening. Some nutrients found to activate the telomerase enzyme include: folic acid, resveratrol, Green tea extract, Vitamin E, Vitamin D, Vitamin C, Carnosine, arginine (by increasing NO which in turn stimulates telomerase), N-acetyl-carnitine and N-acetyl-cysteine. " 20.
"Studies have found that as the body ages, concentrations of carnosine begin to decline. However the body's requirement for this amino acid does not diminish." 21.
"As the body ages, l-carnosine concentrations decline for a couple of reasons. Firstly, the body makes less of this amino acid. Secondly, l-carnosine becomes more susceptible to destruction in older bodies. Studies have shown that people experiencing unnaturally accelerated aging due to conditions such as metabolic syndrome and diabetes have a much lower rate of l-carnosine and this amino acid is destroyed at a faster rate." 22.

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"Context: Although telomeres are “sacrificial” DNA without any necessary genetic content, each time a cell divides, telomeres get shorter. When they decrease to a critical length, cell division ceases and cells becomes inactive or “senescent” or dies. This process is associated with aging. To some extent, the process of telomere shortening is slowed by the enzyme telomerase, whose purpose it is to add telomere length to DNA. Certain nutraceuticals have been shown to activate telomerase, and extend telomere length. While this will not make cells immortal, it may extend their lifespan. Objectives: The study intended to examine the effectiveness of a multivitamin formulated to extend telomere length, and ascertain the viability of conducting a larger, randomized, controlled trial in the future. Design: The study a 90-day, open-label pilot. Participants: Generally healthy men and women older than 18 years. Intervention: All subjects received a 90-day supply of the multivitamin, and were instructed to take one table, three times daily with meals. Outcome measures: The endpoint was absolute telomere length, measured with the quantitative real-time polymerase chain reaction (qPCR) method, using a DNA sample from a buccal (inner-cheek) swab of each subject. Results: 10 subjects completed the protocol. 8 of the 10 had notable increases in telomere length. The mean increase in telomere length for all subjects was 55.86%. Conclusions: The current pilot trial demonstrated the efficacy of the multivitamin in lengthening the telomeres. These findings suggest that is worthwhile to conduct a larger, randomized, controlled trial to measure the telomere lengthening effects of the multivitamin formula." 23.

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" Dietary sources of l- carnosine

Protein-rich foods have a high concentration of carnosine. The best sources of this amino acid are poultry, pork, and beef. Vegetarian sources rich in alanine and histidine to produce carnosine include nuts,seeds,watercress,brewers yeast, brown rice, whole grains, avocado, beans, bran, corn, legumes, mushrooms, and spirulina." 24.

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"A telomere is a repeating DNA sequence (for example, TTAGGG) at the end of the body's chromosomes. The telomere can reach a length of 15,000 base pairs. Telomeres function by preventing chromosomes from losing base pair sequences at their ends. They also stop chromosomes from fusing to each other. However, each time a cell divides, some of the telomere is lost (usually 25-200 base pairs per division). When the telomere becomes too short, the chromosome reaches a "critical length" and can no longer replicate. This means that a cell becomes "old" and dies by a process called apoptosis. Telomere activity is controlled by two mechanisms: erosion and addition. Erosion, as mentioned, occurs each time a cell divides. Addition is determined by the activity of telomerase." 25.

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"The telomere is involved in several essential biological functions. It protects chromosomes from recombination, end-to end fusion, and recognition as damaged DNA; provides a means for complete replication of chromosomes; contributes to the functional organization of chromosomes within the nucleus; participates in the regulation of gene expression; and serves as a molecular clock that controls the replicative capacity of human cells and their entry into senescence." 26.

"In humans the telomere sequence is TTAGGG. This sequence is usually repeated about 3,000 times and can reach up to 15,000 base pairs in length." 27.
The TTA  DNA codon is for the amino acid,Leucine, while the GGG DNA codon is for the amino acid,Glycine. 28.
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"Five amino acids, Alanine, Cysteine, Glycine, Serine and Threonine are broken down to yield Pyruvate. Tryptophan is included in this group since one of its breakdown products is Alanine, which is transaminated to Pyruvate. Alanine is important in intertissue nitrogen transport as part of the Glucose-Alanine cycle. Alanine s catabolic pathway involves a simple Aminotransferase reaction that directly produces Pyruvate. Generally Pyruvate produced by this pathway will result in the formation of Oxaloacetate, although when the energy charge of a cell is low the Pyruvate will be oxidized to CO2 and H2O via the PDH complex and the TCA cycle. This makes Alanine a glucogenic amino acid. Serine is converted to Pyruvate through dehydration by Serine Dehydratase. This PLP-enzyme, like the amino-transferases, functions by forming [...]" 29.

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"Shelterin (also called telosome) is a protein complex known to protect telomeres in many  eukaryotes from  DNA repair mechanisms, as well as regulate  telomerase activity. In mammals and other eukaryotes, telomeric DNA consists of double- and single-stranded TTAGGG repeats and a single-stranded, G-rich overhang. Subunits of shelterin bind to these regions and induce the formation of a t-loop, a cap structure that deters DNA-damage-sensing machinery from mistakenly  repairing telomeres. The absence of shelterin causes telomere uncapping and thereby activates damage-signaling pathways that may lead to  non-homologous end joining(NHEJ),  homology directed repair (HDR), [1]  senescence, or apoptosis." 30..

Given the aforementioned, the enhancement of the performance of and regulation of the telomere, shelterin, telomerase complex is an appropriate approach to the problem of life extension and life enhancement.
The complexity  of the biochemical, enzymatic, biophysical, and electromagnetic interactions requisite for said effective regulation and performance enhancement implies that means to address the same are through biochemical, biophysical, electromagnetic, and genetic approaches which increase the resistance of the same to mutations and other alterations.
This requires research into genetic, biochemical, electromagnetic, and biophysical means to do the same.
With past successful similar interventions on similar complex systems as a guide, this approach should be productive.

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"Niacin cannot be directly converted to nicotinamide, but both compounds are precursors of the  coenzymes  nicotinamide adenine dinucleotide (NAD) and  nicotinamide adenine dinucleotide phosphate (NADP)  in vivo. [5] NAD converts to NADP by phosphorylation in the presence of the enzyme  NAD+ kinase. NADP and NAD are coenzymes for many  dehydrogenases, participating in many hydrogen transfer processes. [6] NAD is important in catabolism of fat, carbohydrate, protein, and alcohol, as well as cell signaling and DNA repair, and NADP mostly in anabolism reactions such as fatty acid and cholesterol synthesis. [6] High energy requirements (brain) or high turnover rate (gut, skin) organs are usually the most susceptible to their deficiency. [7]
Niacin supplementation has not been found useful for decreasing the risk of  cardiovascular disease in those already on a  [8] but appears to be effective in those not taking a statin. [9] Although niacin and nicotinamide are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects (lipid modifying effects) as niacin. Nicotinamide does not reduce cholesterol or cause  flushing. [10] As the precursor for NAD and NADP, niacin is also involved in DNA repair. [11] [12]" 31.

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"Since a large number of oxidoreductases use NAD+ and NADH as substrates, and bind them using a highly conserved structural motif, the idea that inhibitors based on NAD+ could be specific to one enzyme is surprising. [81] However, this can be possible: for example, inhibitors based on the compounds  mycophenolic acid and  tiazofurin inhibit  IMP dehydrogenase at the NAD+ binding site. Because of the importance of this enzyme in  purine metabolism, these compounds may be useful as anti-cancer, anti-viral, or  immunosuppressive drugs. [81] [82] Other drugs are not enzyme inhibitors, but instead activate enzymes involved in NAD+metabolism.  Sirtuins are a particularly interesting target for such drugs, since activation of these NAD-dependent deacetylases extends lifespan. [83] Compounds such as  resveratrol increase the activity of these enzymes, which may be important in their ability to delay aging in both vertebrate, [84] and invertebrate  model organisms. [85] [86]" 32.

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"The 2006 e-publication Nicotinamide extends replicative lifespan of human cells reports “We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.
Another possible longevity contribution of nicotinamide is via autophagy as related in the 2009 publication  Nicotinamide enhances mitochondria quality through autophagy activation in human cells.  Nicotinamide (NAM) treatment causes a decrease in mitochondrial respiration and reactive oxygen species production in primary human fibroblasts and extends their replicative lifespan. In the current study, it is reported that NAM treatment induces a decrease in mitochondrial mass and an increase in membrane potential (DeltaPsim) by accelerating autophagic degradation of mitochondria.” 
I note that these two studies as well as some others commenting on possible longevity benefits of niacin/niacinamide supplementation are in-vitro and the results may or may not apply in human bodies because of the many complex biochemical feedback loops involved." 33.

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How does coffee affect telomeres, longevity, and growth hormone?

Niacin as nicotinic acid is a stimulator of growth hormone (GH) secretion. 34.

"Here’s one virtue of coffee, it contains all the niacin you’ll need for the day. Before you give the green light to your daily cup of java, consider that the low calorie count only refers to black coffee, and the caffeine it contains can be problematic for the body. It also has a dehydrating effect on the body. Serving Size (cup), Niacin (39.73 milligrams), 1 calorie." 35.

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"Scientists have found that telomerase, the enzyme that repairs and regulates telomeres, is controlled and activated by hormones.  Therefore, in order to keep ourselves healthy and with a high quality of life, I believe we must maintain all our hormones at optimal levels. Letting those hormones drop is to let the telomeres get short. When telomeres get short, cells age. Aging causes disease, and death follows.  Studies show that optimal levels of the hormones testosterone and estrogen levels help preserve telomere length.
Optimal Human Growth Hormone (HGH) levels are also associated with telomere length.  A 2009 study published by The Journal of Clinical Endocrinology   Metabolism looked at 2744 men and found that telomere length was positively associated with serum IGF-1 levels.  IGF-1 is the indirect measurement of Human Growth Hormone (HGH) in the body. This positive association is reassuring to me when it comes to optimizing HGH levels." 36.

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"A study by Dr. Gomez Garcia and colleagues at the University Hospital La Paz has research that’s beginning to unmask the truth about HGH benefits when it comes to telomere repair. In the La Paz study and in several other supporting papers, HGH was actually shown to “up-regulate and to promote” a key enzyme called telomerase that intervenes and helps to repair damaged tissue." 37.

Thus, the relatively high concentration of niacin in coffee results in the increased production of human growth hormone which results in increased telomerase which results in decreased telomere attrition which results in increased longevity and decreased morbidity.

Reference 34, "18 Foods High in Niacin to Meet Your Daily Vitamin B3 Needs", lists other foods high in niacin. However, coffee has, by far, the highest concentration of niacin of the foods listed.
"The government-recommended daily allowance (RDA) for niacin/niacinamide is 16 mg a day for men, 14 mg for women." 38.
Thus a cup of black coffee provides all of your daily niacin needs and more!

Both Carnosine and growth hormone levels decrease significantly with age. L-Alanine is the limiting factor in the biosynthesis of Carnosine. Niacin increases the biosynthesis of alanine aminotransferase which produces L-Alanine. The  blood level of Niacin is, therefore, directly related to the blood level of both L-Alanine and Carnosine.

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" Results: ALT levels decreased with increasing age, with mean ALT levels (IU/L) of 23,21,20, and 17 for those between quartile ages 30-62, 63-71, 72-77, and 98-93 years (p<0.0001). Trends of decreasing LSM ALT with age and the decreasing prevalence of categorically  defined elevated serum ALT with age remained robust after adjusting for sex, alcohol use, metabolic syndrome components, and biomarkers of adiposity (p-value <0.0001), and was not materially changed after adjusting for bilirubin, GGT, and albumin.

Conclusions: ALT levels decrease with age in both men and women independent of metabolic syndrome components, adiposity signaling biomarkers, and commonly used liver function tests. Further studies are needed to understand the mechanisms responsible for a decline in ALT with age, and to establish the optimal cut-point of normal ALT in the elderly." 39.

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"Time on Niacin when people have Alanine aminotransferase increased *:

 1 month: 25.0 %
1 - 6 months: 25.0 %
6 - 12 months: 12.5 %
1 - 2 years: 25.0 %
2 - 5 years: 0.0 %
5 - 10 years: 12.5 %
10+ years: 0.0 %
Gender of people who have Alanine aminotransferase increased when taking Niacin *:

female: 34.85 %
male: 65.15 %
Age of people who have Alanine aminotransferase increased when taking Niacin *:

0-1: 0.0 %
2-9: 0.0 %
10-19: 0.0 %
20-29: 1.85 %
30-39: 3.7 %
40-49: 12.96 %
50-59: 24.07 %
60+: 57.41 %"  40.

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"NAD+ levels markedly decline with age, creating an energy deficit that decreases the body’s ability to retain youthful function.
To give you an idea how impactful NAD+ can be, by age 50 a typical person may have only half the NAD+ they did in youth. By age 80, NAD+ levels drop to only 1% to 10% expressed in youth.
Deficiency of NAD+ predisposes us to accelerated aging and impedes our ability to fully benefit from resveratrol.
Fortunately, it is easy to restore your cellular NAD+ to higher ranges.
As a co-factor in cell energy transfer, NAD+ plays a critical role in regulating aging processes.
NAD+ is the acronym for nicotinamide adenine dinucleotide.
Found in virtually all living cells, NAD+ is essential to sustaining life.
A fascinating aspect of NAD+ is its dual role in protecting against factors that age us. This includes mitigating chemical stress, inflammation, DNA damage, and failing mitochondria.
At the same time, NAD+ promotes longevity by facilitating DNA repair and providing cellular benefits associated with caloric restriction and exercise.
In other words, while a decline in NAD+ levels may negatively influence lifespan, restoring NAD+ is increasingly being viewed as a cutting-edge tool to promote longevity.
There is growing evidence that supplementing with a vitamin-like precursor of NAD+ called nicotinamide mononucleotide can promote longevity in life forms ranging from simple worms to mammals like mice.5-11
One study showed an average 5% increase in the lifespan of old mice—even though supplementation did not begin until the mice were nearing the end of their natural lifespan (24 months).
That would be the equivalent of gaining nearly an additional four years of life based on today’s average human expectancy of 78.8 years.
A rigorous scientific review of NAD+ reveals that its longevity benefits arise from eight different, but interrelated, functions." 41.

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"NAD+ beneficially enhances eight core cellular anti-aging mechanisms.
When these cell functions are impaired, the consequence is accelerated aging that contributes to disorders as diverse as Alzheimer's and osteoporosis.
Restoring cell NAD+ levels has been shown to preserve youthful function-and even reverse some age-induced deterioration.
Nicotinamide mononucleotide has been shown not only to restore NAD+ levels in tissues, but also to provide more NAD+ activity that can be obtained from diet alone.
Supplementation with nicotinamide mononucleotide  can slow cellular aging and improve many metabolic defects common to degenerative processes, including diabetes, declining heart function and neurodegenerative conditions." 42.

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"How to Boost NAD+

NAD+ is biologically unstable, which makes it unsuitable for oral supplementation.
Fortunately, there is a solution.

Oral Nicotinamide Riboside, NR, an NAD+ precursor vitamin, has "distinct and superior pharmokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100,300, and 1,000 mg of NR produce dose-dependent increases in the blood NAD+ metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotie (NAAD), which was not thought to be enroute for the conversion of NR to NAD+, is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD+ repletion." 43.

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"Here is a quick breakdown of the key differences between nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR):
NR is a proven form of vitamin B3, which is required to sustain healthy living. It is shown in multiple human studies to effectively increase NAD levels.
NMN is not a form of vitamin B3, and there are no clinical trials to prove it increases NAD in humans. NMN is also not the type of molecule that would ever be considered as a vitamin as it contains a phosphate, which affects its ability to enter cells.
NR is the largest is  part of NAD that can enter the cell. That is why NMN  supplements turn into NR first before that are able to make NAD.
In it supplement form, NMN must become NR first before entering the cell. Then once inside the cells, it converts back into NMN to make NAD. This is a 3-step and rather inefficient process.
NR can directly access the cell, so it only requires two steps to begin creating NAD."
NMN's only published trials are in mice and rats. NR has at least 4 published clinical trials and all of them confirm is a safe and effective way of increasing nad in people.
Despite NMN being sold as a pill to people. NMN is frequently studied through injections in rodents. In preclinical NR trials, it's most commonly added to food or water. Plus, in all of NR's published human trials it was administered in capsule form, which represents the recommended way of taking NR as a vitamin.
There are no published data to show how NMN affects human NAD levels." 44.

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"Nicotinamide mononucleotide, NMN,is a nucleotide derived from ribose and nicotinamide. Like nicotinamide riboside, NMN  is a derivative of niacin, and humans have enzymes that can use NMN to generate nicotinamide adenine dinucleotide (NADH).
Because NADH is a cofactor for processes inside mitochondria, for sirtuins, and for PARP, NMN has been  studied and hyped as a potential neuroprotective and anti-aging agent." 45.

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"The new study, in Cell, found that boosting mice’s levels of the naturally occurring molecule NMN, which humans also have, increased levels of another called NAD+. That, in turn, raised levels of a famous anti-aging enzyme called SIRT1, which has been the focus of nearly 30 years of research.
After two months of NMN, more blood vessels sprouted in the old mice’s muscles. The density of the smallest vessels — capillaries — became comparable to that of young mice. Blood flow increased, and the animals’ endurance, measured by how long they could run on a treadmill before becoming exhausted, was 56 percent to 80 percent greater than that of untreated old mice: 1,400 feet compared to 780 feet.
The treated mice also benefitted from exercise like mice half their age. In young animals, exercise spurs the creation of new blood vessels and boosts muscle mass, but that effect weakens with age in both people and mice. NMN restored the blood-vessel- and muscle-boosting effects of a good treadmill run, basically “reversing vascular aging in the mice,” said study co-leader David Sinclair of Harvard Medical School.
Opinions differed on how important that is. One expert on the biology of aging said, “So David’s found another molecule that prevents aging?” (Sinclair was a prominent exponent of resveratrol, a compound that slowed aging in mice but proved disappointing in people.) The Jax’s Harrison questioned whether the inbred mice used in the study were representative of humans, who are genetically diverse." 46.


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"8 Benefits of NMN

Quite remarkably, this study showed that old mice could be made young, thin, and energetic again with NMN.  Indeed, they convincingly showed that you could reverse aging with NMN.  Below are the eight key findings of this study.
1. Lower body weight
In this study, mice fed low-dose NMN lost 4% of their body weight.  Those fed high-dose NMN lost 9% of their body weight.
To translate these findings, a 9% weight loss in a 200 pound person would be the equivalent of losing 18 pounds.  Even more remarkable was that even though the mice on NMN ate much more, they still lost weight!
2. Increased energy/better mitochondrial function
The mitochondria is the energy power plant of cells.  In this study, mice given NMN were much more energetic and had better energy production from their mitochondria.
3. Less diabetes
Mice on NMN showed much better insulin sensitivity.  Better insulin sensitivity means less diabetes.  Even heavier mice on NMN showed better insulin sensitivity.
4. Lower cholesterol and triglycerides
Researchers found that NMN also dropped cholesterol and triglyceride levels.  However, this drop was primarily seen in those mice on high-dose NMN.
5. Less activation of aging genes
As NMN and NAD both activate the SIRT1 longevity gene, these Washington University researchers observed marked activation of longevity genes and suppression of aging genes.
6. Improved eye sight
Researchers found that the retinas in mice functioned much better with NMN supplementation.  Also, the older mice were even less likely to suffer from dry eyes.
7. Increased bone density and muscle
Mice treated with NMN also had stronger muscles and bones.  Interestingly, the 513 genes that cause loss of muscle and bone density with aging were all suppressed with NMN in this study.
8. Better immune system function
Lastly, NMN treated mice showed better immune function.   Better functioning of the immune system means less infections and and less cancer." 47.

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"Summary

"NAD+ beneficially enhances eight core cellular anti-aging mechanisms.
When these cell functions are impaired, the consequence is accelerated aging that contributes to disorders as diverse as Alzheimer’s and osteoporosis.
Restoring cell NAD+ levels has been shown to preserve youthful function—and even reverse some age-induced deterioration."48.
Nicotinamide riboside has been shown not only to restore NAD+ levels in tissues, but also to provide more NAD+ activity than can be obtained from diet alone.
"in particular, the researchers compared the ability of all three NAD+ precursor vitamins-NR,niacin, and nicotinamide-to boost NAD+ metabolism and stimulate  the activity of certain enzymes,which have been linked to longevity and health benefits. The study showed for the first time that oral NR is superior to nicotinamide, which is better than niacisn in terms of the total amount of NAD+ at an equivalent dose. NR was also the best of the three in stimulating the activity of sirtuin enzymes. However, in this case,, NR was the best at stimulating sirtuin-like activities followed by niacin, followed by nicotinamide." 49.

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Thus, oral nicotinamide riboside, which is available over the counter in pill form, is the best supplement to take orally to increase NAD+ levels.

"High niacin foods include fish, chicken, turkey, pork, beef, mushrooms,brown rice, peanuts, avocados, green peas, and avocados.  The current dail value (%DV) for niacin is 16 mg."  51.
"Fortunately, NMN is found naturally in many foods. Below are the six foods highest in NMN: 1. Broccoli ;2. Cabbage; 3. Cucumber; 4. Endamame; 5. Avocado; 6. Tomato." 50
Good sources of alanine are meat, poultry,eggs, diary products, and fish. Some protein-rich plant foods like avocado also supply alanine." 52.

Therefore, given the aforementioned, it is imperative to increase the bloods concentrations of L-alanine, Niacin,Nicotinamide riboside (NR) and alanine amino transferase in order to minimize morbidity and mortality in humans, especially in the elderly.










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