Chapter 6. : Summary and Conclusion

 This Summary and Conclusion focuses on the individual chapters of this book and the most relevant definitions, terminologies, facts, hypotheses, developments, and conclusions contained in the same.

In Chapter One,"Human Aging,Longevity, Death and Life Extension Defined", the physiological,biological, biochemical,psychological, social, and medical effects of the same are defined,discussed and interrelated.
The individual has choices to make with regard to how he or she can address, ameliorate, and/or prevent anomalies associated with the same. The following are quotes from the end of the chapter which specifically addresses these issues:
What can an individual do to address the aforementioned vascular stiffness, it's associated widened pulse pressure and associated cardiovascular anomalies?
Generally the following will modulate vascular stiffness and it's associated cardiovascular anomalies as well as increase the chances of an overall healthy aging experience: 1. Monitor and appropriately address blood pressure problems; 2. Monitor and appropriately address blood sugar problems; 3. Adequate sleep; 4; Adequate exercise; 5. Monitor and maintain an appropriate weight;6. Don't smoke; and 7.. Have an adequate and well balanced diet. 8. Have regular check ups with your physician."No matter what your age, you have the power to change many of the variables that influence how long you live, and how active and vital you feel in your later years.

"No matter what your age, you have the power to change many of the variables that influence how long you live, and how active and vital you feel in your later years. Actions you can take to increase your odds of a longer and more satisfying life span are really quite simple:

1. Don't smoke.
2. Enjoy physical and mental activities every day.
3. Eat a healthy diet rich in whole grains, vegetables, and fruits, and substitute healthier monounsaturated and polyunsaturated fats for unhealthy saturated fats and trans fats.
4. Take a daily multivitamin, and be sure to get enough calcium and vitamin D.
5. Maintain a healthy weight and body shape.
6. Challenge your mind. Keep learning and trying new activities.
7. Build a strong social network.
8. Follow preventive care and screening guidelines.
9. Floss, brush, and see a dentist regularly.
10.Ask your doctor if medication can help you control the potential long-term side effects of chronic conditions such as high blood pressure, osteoporosis, or high cholesterol." 1..

The following quote is a more specific answer to how vascular stiffness and it's associated wide pulse pressure and cardiovascular anomalies can be appropriately addressed.

"Many interventions involving lifestyle and dietary modifications, for example, smoking cessation [68], use of unsaturated fatty acids [69], isoflavones (abundant in soy beans) [70], reduced dietary salt intake [71], regular cardiovascular exercise [72], and moderate alcohol consumption [73, 74] have all been linked to reducing vascular stiffness. Other strategies involve pharmacologic interventions like calcium channel blocker, diuretics, ACE inhibitors, beta-blockers, nitrates, phosphodiesterase-5 inhibitors, and statins. Even though all these therapies lower blood pressure, their effect on arterial stiffness is only modest." 2...

Chapter two, Aging at the Molecular and Cellular Level, interrelates and describes the complex biochemical, physical, medical, biological, and genetic-genomic changes associated with aging.
Understanding aging at the molecular and cellular level provides the basis for both the understanding of aging, scientific investigation of how the same can be ameliorated or reversed, and the appropriate systematic application of medical and pharmacological means to to ameliorate and or reverse aging and the diseases and disabilities associated with the same.
With regard to the same the following quote is appropriate:
"This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects." 3.
In summary of the aforementioned, the 9 hallmarks of aging at the molecular and cellular level are: 1. Stem Cell Exhaustion; 2. Altered inter-cellular communication; 3. Genomic Instability; 4. Telomere attrition; 5. Epigenetic alterations; 6. Loss of proteostasis; 7. Deregulated nutrient sensing; 8. Mitochondrial dysfunction and,; 9. Cellular Senescence. 4.
NAD+ is the acronym for nicotinamide adenine dinucleotide.

In Chapter three, Life Style and Life Extension, discusses aging with regard to determinants under the control of individuals which can result in life extension, healthy aging, and the prevention of accelerated aging.
The following is an appropriate quote from the same
:"Aging is defined as the progressive decline in physiological functions which leads to increased vulnerability to diseases and death [1]. This is a universal process underlying by many mechanisms and different pathways, whose burden rises to three different phenotypes: normal aging, accelerated aging and successful aging  2]. Despite variability among definitions, “successful aging” is as a multidimensional process encompassing major chronic diseases, major impairments in cognitive, in physical function and sustained engagement in social and productive activities [2, 3]. However, reaching old age in good health is not just a “fate effect” but the result of a complex interweaving between environmental and genetic factors [ 4]. Studies conducted in twins have estimated that approximately 20-30% of an individual's lifespan is related to genetics, while the rest is due to individual behaviors and environmental factors [ 5, 6]. In this contest, nutrition and lifestyle are the most important contributors to longevity and healthy aging [ 7-11]. Follow a diet rich in vegetables, fruits, nuts, olive oil, fish, a small amount of red wine and exercise at least 20 minutes a day three times a week, avoiding obesity, smoke and alcohol, represents the working recipe for long and healthy life. Many mechanisms and pathways underlie nutrition, lifestyle and longevity including telomere length modulation [ 12- 15]." 5.

Chapter Four, Dietary and Medical Interventions for Life Extension, describes medical, biochemical, and other interventions which promote life extension, healthy aging, and prevent accelerated aging.
Included in the same are the following statements, arguments, and facts:
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." 6.
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 than 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." 7.

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." 8..

Long Quote

"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." 9..

Chapter Five, Further Means for Life Extension and Healthy Aging, describes the rapid recent genetic, biochemical, medical and biological advances which have been made to promote life extension and healthy aging which have not been described in the previous chapters.
The following summarizes this chapter:
As one ages, both the efficiency and efficacy of an individuals intermediary metabolism decreases.
As enzymatic reactions are the basis of metabolism and intermediary metabolism, their degradation, efficacy, and efficiency with age must be assertively addressed in order improve both longevity and healthy aging.
Therefore preserving and enhancing enzyme activity and biochemical stability is both a problem and a goal which must be addressed with regard to life extension and healthy aging.
Genetic engineering might prove to be a means to address the problem of telomere degradation along with other associated biological, biochemical, genetic, and biochemical deficits associated with the
aging process.
What is "genetic engineering"?

Long Quote

"Genetic engineering, also called genetic modification, is the direct manipulation of an organism's  genes using  biotechnology. It is a set of technologies used to change the genetic makeup of cells, including the transfer of genes within and across species boundaries to produce improved or novel  organisms. New  DNA is obtained by either isolating and copying the genetic material of interest using  recombinant DNA methods or by  artificially synthesizing the DNA. A  construct is usually created and used to insert this DNA into the host organism." 10.

End of Long Quote

Telomerase, telomeres, and other genetic entities associated with aging might be appropriately modified using recombinant DNA methods and/or by artificially synthesizing the DNA.
"With advanced age, cell NAD+ levels plummet to near zero. Normal aging may one day be classified as “NAD+ deficiency syndrome.”Fortunately, there are proven ways to boost NAD+ levels." 11.
Therefore, given the aforementioned, artificial means might be developed to enhance the enzymatic pathways both to NAD+ biosynthesis along with the biosynthesis of NMN.
Oral ingestion of NMN and Nicotinamide Riboside supplements may prove useful.
However, the biosynthesis of NAD+, NAD+ substitutes, NAD+ precursors, and NAD+ enzymatic utilization enzymes might prove to be an appropriate approach to effectively address
the metabolic and physiological aging problems associated with the severe depletion of NAD+ associated with advanced age.
Therefore, given the aforementioned, it is imperative to increase the bloods concentrations of L-alanine, Niacin,Nicotinamide mononucleotide (NMN) and alanine amino transferase in order to minimize morbidity and mortality in humans, especially in the elderly.
"CRISPR technology is a simple yet powerful tool for editing genomes. It allows researchers to easily alter DNA sequences and modify gene function. Its many potential applications include correcting genetic defects, treating and preventing the spread of diseases and improving crops. However, its promise also raises ethical concerns.
In popular usage, "CRISPR" (pronounced "crisper") is shorthand for "CRISPR-Cas9." CRISPRs are specialized stretches of DNA. The protein Cas9 (or "CRISPR-associated") is an enzyme that acts like a pair of molecular scissors, capable of cutting strands of DNA." 12.
Therefore, given the aforementioned, it is imperative to increase the bloods concentrations of L-alanine, Niacin,Nicotinamide mononucleotide (NMN), Nicotinamide Riboside and alanine amino transferase in order to minimize morbidity and mortality in humans, especially in the elderly.
Given the aforementioned, rapid advances in the fields of life extension and healthy aging will be forthcoming fairly rapidly. The complex scientific and medical advances associated with the same are associated with complex ethical concerns especially with regard to application to the human genome.
It is imperative for the scientific and medical communities to closely monitor these scientific and medical advances so as to appropriately apply the same appropriately and ethically to the wide variety of medical problems facing humanity as well as to how to ethically advance human longevity, healthy aging, and life extension.

" Life is short, and Art long; the crisis fleeting; experience perilous, and decision difficult. The physician must not only be prepared to do what is right himself, but also to make the patient, the attendants, and externals cooperate." Hippocrates