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2016 Reminder Healthy Living Can Add Up To 14 Years to Your Life

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The Ethics of the Future: Human Genetic Engineering and Human Immortality Medicine is Coming in 19 years!!

Posted: January 1, 2015 at 12:46 pm

The Ethics of the Future: Genetic Engineering and Immortality Medicine

2015 is Going to Be a Fascinating Year for Longevity Science

By Professor Mark

How do you feel about the potential for great advances in Human Longevity Science that have been occurring in recent years? Do you feel excited about the prospect of living a much longer life, or are you indifferent? Are you nervous about the prospects of what this sort of tinkering with genetics and human nature might bring?

Is the potential for a vastly expanded lifespan going to be something that everyone can enjoy, or will it be an advantage simply for those that can afford it? If you could live 100 years longer, would you want to? Would you care if the opportunity were afforded to you as an individual? Would such a huge opportunity lead to a new and beautiful life on earth, or would earth somehow take these momentous advantages and turn the world on its head?

My Beliefs Regarding Advanced Genetic Engineering

Many years ago, when I was an undergraduate at Penn State, our professor posited similar questions in our Genetics Class, which played a major role in affecting my beliefs toward the subject of hyper-longevity and Genetic Engineering. The class was large, with more than 100 students, and my professor asked the class what their opinions were regarding the use of genetic manipulation and engineering to alter human life.

Surprisingly, the class was completely silent. In response to this silence, the professor called up two students to debate the subject. One of my classmates volunteered to voice his opposition to genetic engineering, and I chose to volunteer, providing an argument in favor of it.

My opponent voiced his opinion to the class that genetic engineering for this purpose would be ethically wrong because it is not in man’s best interest to play God. Most of our classmates seemed to agree, nodding subtly in agreement.

Personal Aesthetic: Choosing to Be Different

I felt as though I was standing upon a grand crossroads of history. As I looked around the class, it felt as though all of my classmates, for all of their cliquish differences, were being incredibly closed-minded, like they just accepted what they had been told all their lives and were afraid to think for themselves.

After the professor gauged the response of the students, I had my opportunity to argue in favor of this advanced human genetic engineering. I glanced around the class, and felt my argument come together cleanly in my mind. I saw white girls with bleached hair stretching down their backs, more than a few of which had fake breasts. I saw black girls with expensive weaves and complex and expensive hairstyles.

There were white students mimicking their hip hop and rap idols, and I even saw a young Asian student that had very obviously dyed her hair red. In my class I saw a great commingling of different styles. People both attempting to exemplify American standards of beauty and those taking on the aspects of other cultures, adopting them as their own.

As I looked around at all of this, recognizing the great diversity in my class, I had a strong feeling that there was not one person in the class that didn’t have at least one thing they wanted to alter about the characteristics they were born with. I continued thinking to myself, that these students probably wanted to be different in a variety of different ways: some wanted to be smarter, some taller. Some girls wish they had larger breasts, and some guys wanted larger penises. Others probably wish that they didn’t have to go through the trouble to put in contacts and hair dyes to look like the person they wish they were. For myself, I would have given anything just to be a few inches taller.

A Call for Genetic Freedom

After standing quietly for a moment, with all of these thoughts running through my at head a rapid place, I spoke from my position, in the back of the class, and suddenly stated loudly: Genetic Freedom!

I felt that just those two words spoke for themselves, but my professor threw a dejected glance in my direction, and I could detect her shaking her head almost imperceptibly. Her silence was a sign that she needed more. After the brief silence, I continued. I argued to the class that the individual should have full control to alter his DNA as he sees fit, so long as it doesn’t negatively impact society or the rights of anyone else.

She seemed thoroughly unhappy with the argument, and the class began to chatter loudly, nearly in unison. After the short spate of controlled chaos, the class continued with liveliness and energy, but I felt that others in the class largely shunned me as a result of the fervent beliefs I expressed in regard to what legitimately amounted to the potential future of the human race.

Will People Be Able to Resist Genetic Alteration?

I still laugh to myself to this day about how my belief met such incredulity in the face of so many. In the future, once science makes it possible to make such powerful changes to humanity at the genetic level, I am confident that these same students, if given the actual opportunity to improve themselves through futuristic genetic methods, would absolutely jump at the chance with no second thought.

It wouldn’t be Playing God. It wouldn’t be unethical. It would simply be the new reality. In fact, once the time comes to pass when Genetic Alteration becomes a reality, the exact same people today that seek out plastic surgery and cosmetic surgery will clamor for these procedures as soon as they become available. In the end, I believe I made a B in the course, which is regretful, because I’ve always remained highly interested in genetics.

The Future of Humanity: The Organic and the Engineered

Another of my professors at Penn State, himself with a doctorate in genetics, explained an interesting aspect of human evolution, one which I had never thought of before. He explained that the many races that make up humanity as a whole developed their differences as a result of dispersing far from one another, and slowly adapting to their new environments over time.

After they migrated, geography, distance, and other factors kept them from interacting heavily with one another, which caused their minor adaptations to become more pronounced. In the same way that they developed their own habits and cultures, their aesthetic and physical makeup also changed. Some grew taller, others grew paler, and each individual culture became maximally resistant to the diseases which were prominent in their area.

Even though these physical and genetic changes were significant, any healthy woman on earth could still mate with any other healthy man, no matter how different he looked or acted. What he said that truly sparked my mind was that if the different races of human beings stayed geographically isolated from one another for longer period of time, eventually the different races could have changed enough to where they could no longer produce children with one another.

Could Genetically Engineered Humans Evolve Beyond Humanity?

This can also apply to the future of genetic engineering. The modern world is so interconnected that geography has no impact on the ability of humans to breed with one another, but genetic enhancement may lead to a point at which a human born today would not be able to mate with an individual that was the result of generations of genetically altered parents.

As Genetic Engineering becomes more advanced, humans may change enough at the genetic level to prevent interbreeding between lineages which have undergone these advancements and those that chose not to. This change would of course be gradual, first reducing the ability to conceive before denying that ability altogether. At this point, it would take genetic engineering just to create a viable child for two disparate humans. Interestingly enough, it may even come to pass that different species of humans evolve from such endeavors, as distinct from one another as they are from humans themselves.

The beginning of this story could begin sometime in the next hundred years, as scientists and medical specialists develop the ability to safely and effectively alter DNA to meet the specifications of the individual.

The Future is Coming: the Great Human Divergence and the Neo-Sapient

The people that choose to reject Genetic Modification and Advanced Longevity Treatments in the near future will create an interesting binary world. This could be the beginning of a grand human experiment. This could be the focal point of a genetic divergence so strong that it literally fragments the human race, creating a new class of post-humans that have advanced to a point where they qualify as their own unique species.

I think back to the genetics course I mentioned earlier. I remember the absolute ocean of diversity that was contained within the 100-student course, and I was able to visualize a future in which Genetic Modification leads to even greater diversity, and a uniqueness that has never existed in the history of the human race. It made me think of the diversity of the universe, and the unlimited options for diversity that it represents. As someone with an affinity for astronomy, I find it utterly inconceivable that planet earth is home to the only lifeforms in the universe.

Of course, along with my great optimism, I do recognize that there are risks and unknowns related to the future of Genetic Modification. There is even the potential that the science behind Genetic Modification could be used for Genetic Warfare. There is certainly the potential that the same science that creates a new humanity could be used to destroy large swathes of it. I can imagine an apocalypse that is not nuclear and grandiose, but genetic and nanoscopic.

Post-Humanism and the Search For Other Worlds

In the end, will humans be able to develop interplanetary travel and colonization in order to insure itself against such potential apocalyptic scenarios? It’s a subject that I am particularly concerned with, and is the core reason why I support NASA and the United States Space Program. As the world moves faster and the dangers become greater, it is imperative that we are able to save humanity even in the case of a state of mutually assured destruction.

If there truly is a Genetic Revolution on the horizon, it is vitally important that we use all of the resources we have available in order to make our dreams of space colonization a reality. Imagine a future so spectacular: A future where a multitude of post-human species advance outward from earth in order to colonize space like a rainbow across the galaxy.

This journey will be arduous and epic, as earthlings spread across the cosmos in order to find new viable homes and potentially interact with other life forms.

What Would Aliens Be Like?

Can you imagine how literally otherworldly that would be? If we found advanced aliens, would they have unlocked the key to eternity? Would we have done the same? There is no doubt that the first time that we make contact with an extraterrestrial species, they will come from worlds and cultures which are absolutely unimaginable in the face of everything that we have experienced.

I may have delved a bit into the realm of science fiction, but the future of humanity in the face of Genetic Modification has the potential to be every bit as exciting and otherworldly as the potential future that I just described. It instills a tremendous sense of fear, awe, and most importantly, unlimited potential.

Do You Think That You Could Handle Immortality?

If you ask the average person out on the street about the potential future afforded by Genetic Engineering, Advanced Longevity, and Immortality medicine, you’ll likely get a number of different responses, some positive, some negative, others simply incredulous. If you surveyed 100 people, I believe that you would find that the majority would ultimately reject the idea of immortality.

Some people think that eternity would take the excitement out of life. Others fear that they would eventually just become a broken shell of their former selves as their bodies physically decline in spite of science’s ability to prevent death. For many, the concept of eternity is just as fearsome as the concept of death itself. It’s not all that different from the way that people feel about retirement these days. They are frustrated because they have to work so hard all through the healthiest part of their lives only to be too frail and broken down by the time they retire to enjoy it.

Longevity Medicine and the Future

That’s why Longevity Medicine is so important. We want our retirement years to last as long as possible, and we want to be able to enjoy them. Maybe one day, we will be retired as long in our lives as we are at work, or longer! That’s what the approach to immortality will be like!

There are a growing number of people that are optimistic about a lengthy future. They understand that even with regard to a concept like immortality, life is the sum of individual experience. Some will take advantage of a life bordering on immortality, while others would simply choose to be boring. People that live lives full of happiness and vitality shouldn’t be deprived the opportunity to extend that joy, simply because there are others who wouldn’t appreciate it!

The arguments stemming from the subject of Human Immortality continue to become both more interesting and more complex, both for those that long for such a fate, and those that oppose the concept. No matter how you feel about the idea of Advanced Longevity, there is no doubt that such opportunities to live lives we now consider unimaginable will eventually come to pass.

As long as human beings are able to engage in scientific advancement without destroying ourselves or sending ourselves back to the stone age, such opportunities will present themselves to the human race in the near future.

Gene Therapy and Stem Cell Therapy: The First Steps to Hyperlongevity

The seeds of these future endeavors are being planted today, in the fields of gene therapy, genetic medicine, and stem cell therapy. This is also the core concept behind medical treatments which seek to optimize hormone production in the body in order to alleviate the medical conditions associated with hormone imbalance and aging.

Hormone Replacement Therapy: Streamline Your Body for the Future!

Treatments such as Testosterone Replacement Therapy, Sermorelin Acetate Therapy, and Bio-Identical Human Growth Hormone Replacement Therapy seek to correct common hormonal imbalances that occur as a result of the aging process. There is even a strong argument that these hormone imbalances are actually the root cause of many symptoms of aging, including frailty, osteoporosis, and cognitive decline.

There are many Health, Wellness, and Longevity Physicians that believe that these forms of Hormone Replacement Therapy are some of the must effective means to prolong a healthy and active life when used in combination with a healthy and conscientious lifestyle. These medical treatments are the best way to decrease your mortality risk so that you are more likely to experience the next great advancement in Anti-Aging Medicine.

If you feel that your quality of life has been on the decline as a result of changes in your body and mind resulting from the aging process, I strongly encourage you to get your hormone levels checked, because there is a significant chance that you may be suffering from a reversible form of hormone deficiency.

The Future of Human Genetic Engineering

This is truly an exciting time to be alive. We are quickly approaching the point at which scientific breakthroughs in health science will continue to occur at an ever-increasing pace, with groundbreaking new health advances occurring on a regular basis. The following years will be incredibly interesting, because there are a multitude of clinical trials regarding the promise and potential effectiveness of both gene therapy and stem cell therapy.

By 2012, these studies, and other similar studies, were already displaying high levels of potential to both treat and protect both animals and humans from disease. Beyond Hormone Optimization and Genetic Therapy, the next stage of advancement will most likely be in the field of nanomedicine. Beyond nanomedicine is femtomedicine.

At this stage of scientific inquiry, this is as far as even the most forward-thinking physician or philosopher could imagine, but there is no doubt as we create new medical treatments and expend our knowledge of medical science, new opportunities for advancement will be conceptualized that could be even more life-altering and fantastic than those that we just mentioned.

When you consider the future of medicine and longevity, you realize that human beings as they are now aren’t simply the end result of millions of years of evolution, but also a gateway to the next state of terrestrial life, a transitional state between what was and what will be, an opportunity to experience even greater consciousness and enlightenment by conquering time, itself.

What is the Idea Behind Human Immortality?

When we discuss the idea of human immortality, it doesn’t just mean allowing a human being to live forever, human immortality represents the idea that it will be possible, with future biomedical and genetic enhancements, for human beings to experience a practical immortality in which one is able to live as they were in the prime of their life, for all of their life.

It seems just as you master your body and your mind in the late twenties and early thirties, your body and mind start to enter a slow and unstoppable decline. What if you could preserve that period of physical and psychological perfection forever? It is during this period that the average person reaches his or her functional peak as an individual, with regard to strength, cognitive ability, immunity, and overall health.

How Much Better Would Life Be if You Lived to 200?

Think about how different and exciting that life would be if you could have the body and mind of a 29 year old for 120 years. There are a number of people that think that humans should not have this opportunity, but it sounds much better than spending the whole sum of those years in slow and steady decline.

How Much Better Would Life Be if You Could Live Indefinitely?

Immortalists subscribe to the belief that individuals that truly enjoy life and are creative or passionate enough to find interesting or fulfilling things to do would be able to easily take advantage of a significantly lengthened lifespan. I do understand how such a long life would feel to someone that lacks passion or imagination, however. I can imagine two hundred years of absolutely drudgery. If one does not have the propensity to invest or save to create wealth, I can imagine two hundred years of hard work with nothing to show for it.

With luck, a more automated world would allow us to enjoy our lives while actually working less. Imagine a world of eco-friendly machines could do the work of one hundred men. This could be a wonderful world of leisure for all, but it could also lead to a world where machines are used as a method of control and domination, like in Frank Herbert’s dystopian novel Dune.

The Temptation of Human Immortality

Whether the opportunity for Human Immortality comes in twenty years or two hundred years, there will be those that seek out the opportunity for such a life, and there will be those that choose to reject the opportunity for immortality.

The central question that Immortalists posit is a simple one: Why would anyone actually want to die or grow old? When you think of it that way, it sounds absolutely silly. Who would ever want to do such things? But in reality, it seems as though most human beings are resigned to such a fate.

Who Really Wants to Grow Old?

More than simply growing old, who wants to lose their lust for life or their libido? Who wants to experience their own body slowly deteriorate as they are beaten down by illness and disease? Human Immortalists are those that are willing to fight against what is perceived as inevitable by society at large. They believe that those that have resigned themselves to decay and death are simply not willing to imagine a post-human age where they could evolve beyond the inevitability of death.

It seems that many humans think of Human Immortalists as harbingers of doom which are going to bring about a new genocide. They believe that Immortalists are going against the will of God by altering the Human Genetic Code in an attempt to foster extreme lifespans, improved aesthetic, and vastly improved health outcomes.

The Great Schism of Humanity

There is a strong chance that a rift will develop between those that choose genetic alteration and those that choose to forgo such opportunities. In the end, it is likely that humanity will rift into two distinct groups. Over time, greater and greater numbers will opt for Genetic Modification, and those that opt out of such procedures may potentially lose footing in society as a result of their choice.

If modification indeed has the ability to create such disparity, genetically modified humans will spread their genes with one another, and their offspring may have greater potential for both prosperity and intellect, which will create a socioeconomic rift between GM Humans and Unmodified Humans.

Will Post-Humans be able to act ethically under these circumstances? Will Unmodified Humans be able to accept a place in the world where they are unequivocally inferior to their GM counterparts? This new world will be different and exciting, and it’s up to us to create a civil world where we can act in the best interest of all.

What Other Strange Opportunities May Become Available in the Future?

On top of our ability to vastly extend and improve our long-term health, the future will also provide us with enhanced opportunities with regard to personal aesthetic. We will not only be able to cure conditions such as psoriasis which plague millions in the world today, but many may choose to move beyond mere optimization and may choose to fully customize their appearance. Perhaps one may choose not to have olive or alabaster skin as many in society desire today, but go for a different color all together.

What if someone chose to color their skin orange, green, or blue? What if they wanted to be leopard print or covered in zebra stripes? This may appear otherworldly and unnatural to our minds, but when presented with an entire array of customization, what would be so strange about doing something like that to stand out? How different would it be to dying your hair blue or rainbow, if there were no dangers in undergoing such a change?

But, given enough time and scientific innovation, skin color and other basic augmentations like genetic breast and penis enlargement will be just another evolution in the concept of general aesthetic. The potential for more extreme changes would eventually become possible. What if humans wanted to take on the characteristics of animals? What if someone wanted the ears or tail of a cat, for example? There would even be the potential to do even more drastic things that we can barely imagine today.

Genetically Engineered Pets

These genetic advancements won’t occur in a human vacuum. They will also apply to animals as well. Today people are paying top dollar for basic genetically modified hypo-allergenic dogs, and glow-in-the-dark mammals have even been developed in laboratories.

In the future, it is likely that scientists will come up with scientific modifications which significantly enhance both the aesthetic and intelligence of animals. It’s even likely that animals will experience the benefits of genetic engineering more quickly than humans, as this future will largely be facilitated by means of animal testing.

The Post-Human Era Starts with Basic Genetic Engineering and Ends with Post-Humanism, Hyperlongevity, and Potential Immortality

You may not be able to tell, but we are already in the midst of the first phase of the Post-Human era. The beginning of this era was marked by the first time that egg and sperm from two different individuals was combined and implanted into an adoptive mother. It was such a grand event in retrospect, but the passing into this new era was not met with massive celebrations, but simply with concerns over the ethics of the new future.

Post-Humanity will have a litany of moral conundrums to unravel, some that we can imagine, and others that are unfathomable to us today. The state of the mortal mind is simply not equipped to handle the moral and ethical quandaries that the genetically modified mind will face. What if there are other lifeforms just like us in other parts of the galaxy, that have also learned to take control of their very existence on the cellular level? What if the number of unique alien civilizations in the universe is unlimited? What if we as earthlings are just one form of intelligent life among a countless litany of others?

The Current State of Genetic Modification and Gene Therapy

Today, scientists, researchers, and physicians are taking the first step into this future, with the quickly growing field of genetic therapy. We are on the cusp of doing some truly amazing things, like genetically altering viruses in order to protect humans from genetic disorders and conditions. At first, these initial treatments have been risky, reserved for those in most dire need, but as medical science becomes more well-versed in these therapeutic advancements, they will become safer and more widely available to the general public. Could you imagine reducing your risk of cancer by 80% just with a single injection? That may be the future for you.

The Current State of Organ Regeneration and Stem Cell Therapy

Another aspect of genetic therapy has to do with the advancing field of Stem Cell Therapy. There are new, state of the art treatments available which utilize stem cells in order to improve the health of the heart. Patients that have experienced heart attack or heart disease can be treated with stem cells which have the ability to develop into new and healthy muscle tissue.

Similar techniques have also been used in order to regenerate other parts of the body or parts of individual organs. In one famous case, scientists biomanufactured a windpipe for a patient with the patient’s own cells. They were able to do this by taking the stem cells and allowing them to grow in culture before pouring them over a scaffold in the shape of a windpipe. Just by providing the cells with the nutrients to grow, they were able to recreate a human windpipe in the laboratory just in a matter of days.

Because the windpipe was created from the patient’s own cells, the body did not reject the windpipe when it was surgically implanted into the body. This is one of the first successful cases where a patient’s life was changed through the scientific advancements of genetic organ replacement.

Stem Cell Therapy Will Be Available in the Near Future: Hormone Replacement Therapy is Here Today!

Stem Cell Therapy is exciting and will become increasingly common and popular over the next century in the United States. Today, there are a few places where Stem Cell Therapy is available internationally, especially in Asia, but they have yet to be medically certified, and there are still a number of pertinent risks involved. In the Western World, Stem Cell Treatments are currently going through clinical trials. Although the results are mixed, continual progress is being made.

There are many scientists that believe that Stem Cell Research will lead to a new future in medicine, but policies enacted during the presidency of George W. Bush have set the United States behind by at least a decade, and other nations in Europe and Asia are currently taking advantage of their head start, and may one day eclipse us in these new and futuristic medical therapies.

In just a few short years, genetic testing will become affordable enough that it will become a common and recommended part of prenatal care as well as regular checkups throughout the lifespan. Over time, more and more Genetic Disorders will be able to be effectively treated with Gene Therapy, and with every breakthrough, people will be that much more likely to live a longer and healthier life.

Once the clinical science is sound, it won’t even be a difficult ordeal for the patient. It would simply be like going to visit the pharmacist, or making a call to a specialist pharmacy. After receiving the medication, one will be able to administer the medication on his or her own and without the frequent oversight of a medical professional.

Not long after these Genetic Treatments are made available to the public, Stem Cell Therapies will quickly become more and more advanced as well. There are even companies that have expressed a desire to take your stem cells and develop them in a laboratory environment. The goal of this treatment would be to take your own stem cells and foster the healthiest cells to multiply. After these cultures are developed, they would be mailed back to you in order for you to inject them to alleviate health conditions and other symptoms related to the aging process.

Beyond Genetic Engineering and Stem Cell Therapies, will come new forms of medical treatment that we are just beginning to research today, but will surely flourish in the coming decades: nanomedicine and femtomedicine.

Nanoscience and the Healthcare of the Future

These are tiny, genetically engineered cellular machines that will be able to improve your health by altering the functions of your body in a positive manner. They will be able to repair and alter particular forms of cells so that they function optimally, even after a period of long life in which you would expect to see physiological breakdown. It is even believed that these treatments can also preserve and repair the brain itself! Isn’t that exciting?

There are countless people in the world that have a litany of big dreams, more than they could ever hope to accomplish in a single lifetime in some cases. They have these long checklists of things they want to do in their life, a whole wide world they want to explore. Some have an unquenchable thirst for knowledge, and want to read thousands of books or learn dozens of languages in their life.

There are countless more people that have spent their early lives living on the edge, and suffer from issues such as alcohol dependency or drug addiction which have harmed their bodies and their brains. With these forms of genetic and nanomedicine, it will be possible to repair the bodies and minds of these individuals, allowing them to make a fresh start. It is possible that addiction itself may become a historical curiosity as a result of these medical advances.

What Would Do If You Had 200 More Years to Live?

  • Would you learn to play multiple musical instruments?

  • Would you research for decades in order to write the perfect novel?

  • Would you visit every country on earth?

The number of dreams that humans have yearned for is nearly infinite, and most never live to achieve all of their dreams, if they achieve any of their dreams at all. If you are still alive in the near future, around 2032, you will be able to take full advantage of what Longevity Medicine and Anti-Aging Therapy have to offer!

Some time in the future, we will finally overcome the condition of aging. We will be able to prevent all illness and be able to live in perpetuity, as long as we don’t succumb to an accident or similar fate. This is the extreme vision of Immortality Medicine.

The First Immortals Could be Alive Today!

By the time we make it to the 22nd century, there will already be individuals that have taken the road to Hyperlongevity, and there will likely be millions of humans that have taken part in this great leap forward into Post-Humanism. They will not only be healthier, but smarter too, with further advances in Genetic Science that allow us to amplify the capacity of our brains.

As people continue to develop down this evolutionary road, will we even consider them humans anymore? They will represent a new version of humanity, and they will likely use a new term to define themselves, whether that be Neohuman or some other clever word or phrase.

I believe that this advance into Neohumanism will also lead to a new era in space travel and human colonization. With these extensive lifespans, many Neohumans will inevitably turn their eyes to the stars in a desire to find new worlds and discover new lands and extraterrestrial lifeforms. Brave Neohumans from all over the planet will take to interplanetary space vessels in order to colonize and experience new worlds and lands that are beyond the scope of human imagination.

Can I Live to Experience This New Era of Humanity?

All of the things we’ve discussed may seem incredibly exciting to you, but we understand that these innovations are going to come in the near future. If you want to take part in this grand human experiment, it’s important that you live long enough to seize these innovations as they come! There are steps you can take now to alleviate the negative symptoms of the aging process and increase your odds of experiencing the new, human revolution.

My suggestions will not ensure that you will live for the next twenty years or longer, but they will potentially drastically decrease your mortality risk so that you are able to seek out this new and exciting future that we have laid before you.

Today, the door to Neo-Humanism, Hyperlongevity, and even Human Immortality is slightly open, and there are many alive today that will experience these magnificent and life-altering advances.

Will You Take Advantage of the Advances of Hyper-Longevity and Anti-Aging Medicine? Are You Willing to Commit to a Longer and more Youthful Life?

It’s quite plain to see that we are at the crest of an event horizon, beyond which it will truly be possible to lengthen lifespans indefinitely. The most important thing is to breach that horizon. By taking steps to increase health and lifespan now, you allow yourself the opportunity to take care of further, greater medical enhancements down the road.

The most modern advances available today are in the form of Recombinant Hormone Replacement Therapies. By optimizing your hormone balance, you increase the odds that you will live long enough to experience the new, up-and-coming breakthroughs of the mid-21st century.

If you live just a few more years, new genetic medical treatments will become available which will significantly increase your lifespan. While you are enjoying the benefit of genetic medicine, researchers and medical scientists will advance and perfect Genetic Therapy and Stem Cell Therapy, allowing you to live even longer!

There are a number of Stem Cell and Gene Therapies going through clinical trials as you read this, which show great promise in preventing or treating serious illnesses which severely inhibit lifespan today. As the medical community becomes more adept at using these new tools for the purpose of treatment, they will begin to utilize these treatments as forms of Positive Medicine.

They will be able to treat patients before they even get sick in order to optimize their health and greatly improve lifespans as a result, because the incidence of illness will decline significantly. In addition, these same treatments will be able to streamline existing physiological processes, keeping the body physiologically stronger and more youthful. They will be able to tailor these treatments uniquely to the individual in order to give the best care to each individual patient.

Stay on the Cutting Edge of Longevity Medicine to Perpetually Extend the Human Lifespan

With each of these breakthroughs and treatments, we will come one step closer to Immortality. Eventually, scientists and researchers will crack the code of human life, and finally figure out how to allow us to truly live indefinitely. It may take 100 years or it may take 500 years to achieve true Immortality, but each life-extending advance will allow people to survive until the next great advance. Hyper-Longevity will eventually become a universal reality, barring accident, war, or any other form of life-ending catastrophe.

You may feel that this is a science fiction world that I am describing, but it very well may be possible for you to experience this all for yourself. It is estimated that at some point between 2032 and 2052 we will have perfected medical practices which allow us to live significantly longer lives than we do today. Those that are optimistic feel that we are just twenty years away from this era, while those that are more cautious suggest that fifty years would be a more reasonable estimate.

Twenty to fifty years may not seem like that long in scientific study, but in terms of your own life, it is a significant period of time. Are you willing to make the sacrifices now in order to experience Hyperlongevity in the near future?

Eight Ways to Extend Your Lifespan

There are a lot of steps that you can take in your life today in order to significantly increase the odds that you survive to experience this new and amazing future. If you follow the suggestions below, conscientiously, you will maximize your potential to extend your life until further longevity advances develop in the coming decades.

These eight factors have been shown to be most important when determining the length of an individual’s lifespan:

  • Nutrition

  • Exercise

  • Environment

  • Social Circles

  • Vice

  • Climate

  • Calorie-Restricted Diet

  • Hormone Replacement Therapy

The Diet of the 21st Century: Caloric Restriction and Fasting for a Longer Life

A recent article in Newsmax Health explained that the future of longevity isn’t fad dieting or strenuous exercise, but a Calorie-Restricted diet which manages metabolism and ensures a long and healthy life.

Over the last century, there have been more than twenty thousand studies regarding caloric restriction in animal species from around the globe. All of these studies have unequivocally shown that restricting the calories in an animal’s diet has the ability to significantly increase the lifespan, and the same appears to apply to human beings..

This may sound like a starvation diet at first, but conscientiously and significantly restricting calories in the human diet is a powerful means to a longer life. Of course, most people consume at least 1500 calories per day and some consume several thousand! But, it appears that the sweet spot for human longevity is quite a bit lower than that 1500 calorie threshold.

For those that are struggling with Caloric Restriction, especially those that are currently overweight, HCG Injections can help relieve the feeling of hunger associated with the initial phase of the diet in order to acclimate to their new dietary lifestyle more effectively.

At first it may seem counter-intuitive, that too much of the Bread of Life can actually shorten the lifespan, but that absolutely seems to be the case. A diet that provides high levels of nutrients through the consumption of a small number of calories is the number one way to increase human longevity effectively. Intermittent Fasting and Caloric Restriction slow down aging and also reduce the incidence of a wide variety of illnesses that plague so many in America today.

The Modern Media and the Culture of Food in the West

In the United States, as well as other countries in the West including the United Kingdom, children were raised in a reality in which starvation was one of the greatest evils of the 19th and 20th century. The various forms of media available all showed the terrible fates of so many who were denied the food needed to live. Nowhere is this imagery more vivid in Western Civilization than in the footage captured after the end of World War II as the true horrors of the Holocaust were revealed to the world at large.

During the Cold War we also experienced further evidence of the horrors of famine as communist Russia and China struggled with providing their populations with proper nutrition, leading countless to die of starvation over many decades. Today, on modern television, there are advertisements for charities throughout Africa and Asia which show the plight of the starving in these third world nations.

I do not mean to discount the real and significant struggles that those that came before us experienced in the not so distant past, but it had a powerful impact on food culture in the West, particularly the idea that it is better to eat too much than too little. In our elementary education and beyond, we are confronted with story after story of mass famine, and it seems that part of the way that we culturally appreciate our current abundance is by partaking in it.

This appreciation for our abundance has led directly to a culture of overeating that borders on obsession. In the West, we simply love our food too much, and the expansion of cuisine in the West has allowed anyone to get whatever they want, when they want it, whether they go to the grocery store, the pizza parlor, or the Chinese buffet.

A Culture of Overeating Develops into a Culture of Force Feeding

Throughout the twentieth century, we have always been taught that we need to eat every last bite on our plates. Often times, we were also strongly encouraged, if not forced, to go back for a second portion. In addition to this, the proliferation of soda drinks has led directly to a significant increase in the empty calories that the average American consumes.

As the twentieth century barreled on, parents on average had less time to cook and prepare meals at home, which led to the greater proliferation of both fast food and microwavable dinners, loaded with sugars, salts, and carbohydrates which increased our caloric consumption even more!

During this age, restaurants like Burger King and McDonald’s became the captains of the fast food industry, generating billions of dollars in profit funneling cheap calories into the mouths of men, women, and children all across the country.

Because of all these pressures to overeat, the longevity gains that people in the West experienced as a result of modernization all began to slip away, the combination of unhealthy eating and an increasingly sedentary lifestyle is threatening today’s generation with the prospect of living shorter lives than their parents on average!

The United States would be stronger in every way, if it could foster greater consciousness about the importance of eating smarter to eat longer. If we all just made the proactive decision to engage in a lifestyle of at least mild caloric restriction, it would both decrease the price of health care and allow the citizens of this nation to live longer, happier, and healthier lives.

Do You Dream of a Healthier, Happier Life? Contact the Conscious Evolution Institute Today!

If you are a man or woman over the age of thirty and currently live in the United States, the Conscious Evolution Institute can help you improve your health and longevity. We provide Doctor-Monitored Bio-Identical Hormone Replacement Therapy to patients all across the United States.

With just a simple phone call, we can arrange for you to meet with one of our affiliate physicians in order to set you on the road to a new you. We offer a variety of Hormone Replacement options, including Testosterone Replacement Therapy, Human Growth Hormone Injections, Sermorelin Acetate Injections, and HCG Injection Therapy for Weight Loss.

We also provide nutrition and lifestyle counseling in order to help you maximize the results of your treatment by choosing foods, supplements, and exercises that will get your body running on all cylinders!

If you feel that you may be a candidate for Hormone Replacement Therapy, don’t hesitate, call us today, and one of our friendly specialists will walk you through the process and answer any and all questions that you may have.

For more information on Ten Ways To Live Ten Years Longer check out

Recommendation and review posted by Guinevere Smith

Integrative Medicine Doctor and Practitioner | Philadelphia

Posted: August 28, 2016 at 12:59 pm

Philadelphia Integrative Medicine combines the best of conventional and alternative medicine to inspire you and give you the tools to care for yourself and be well.

We provide leading edge clinical expertise using a combination of conventional and evidence-based alternative and holistic medicine, to recommend the lifestyle changes, cutting edge diagnostic testing, mind-body practices, supplements and medicines to meet your personal health goals. Our approach helps you achieve better health, including the physical, emotional, psychological and social dimensions.

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: Arizona Center for Integrative Medicine

Posted: August 28, 2016 at 12:59 pm

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This Year in Science | Futurism

Posted: August 28, 2016 at 12:57 pm

This Year in Science The Year of Robot Intelligence

In 2015, the robot revolution enveloped the globe. But the world didnt end. It got better.

In 2015, we turned our gaze back to the stars. And we challenged the frontier once again.

In 2015, fleets of drones took to the skies. But theyre not just war machines anymore.

In 2015, gene editing went mainstream. And it gave us the keys to our DNA.

In 2015, scientists and entrepreneurs of all ages, genders, and backgrounds pushed humanity toward a brighter and smarter future.

But one of them did it a dozen times over.

Our 2015 Futurist of the Year is…

In the words of fictitious astronaut Mark Watney, “We scienced the s**t out of 2015.”

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This Year in Science | Futurism

Recommendation and review posted by Guinevere Smith

Khan Academy

Posted: August 28, 2016 at 12:57 pm

Learn for free about math, art, computer programming, economics, physics, chemistry, biology, medicine, finance, history, and more. Khan Academy is a nonprofit with the mission of providing a free, world-class education for anyone, anywhere.

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Gene Therapy – National Center for Biotechnology Information

Posted: August 27, 2016 at 11:43 pm


Gene therapy is defined as the treatment of disease by transfer of genetic material into cells. This review will explore methods available for gene transfer as well as current and potential applications for craniofacial regeneration, with emphasis on future development and design. Though non-viral gene delivery methods are limited by low gene transfer efficiency, they benefit from relative safety, low immunogenicity, ease of manufacture, and lack of DNA insert size limitation. In contrast, viral vectors are natures gene delivery machines that can be optimized to allow for tissue-specific targeting, site-specific chromosomal integration, and efficient long-term infection of dividing and non-dividing cells. In contrast to traditional replacement gene therapy, craniofacial regeneration seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and replace tissues in vivo.

Keywords: gene therapy, gene transfer, vector design, tissue engineering, virus, regeneration

Human gene therapy is defined as the treatment of disorder or disease through transfer of engineered genetic material into human cells, often by viral transduction. Since the introduction of science fiction, the popular press has toyed with the notion of viral gene delivery and its terrifying implications. One of the more recent popular works on the topic is the 2007 remake of Richard Mathesons classic 1954 novel I Am Legend, which details events following the discovery, release, and mutation of a genetically re-engineered measles virus that was initially hailed as the cure for cancer (Matheson, 1954; Lawrence, 2007). This adapted novel, which has been redone in three instances as a feature film, outlines the seemingly inevitable worldwide destruction that could result from viral gene therapy. With an emotionally stirring history of fictional violence and a debate that provokes both moral and medical issues, it may be surprising that, since 1990, billions of dollars have been spent on hundreds of human viral gene therapy clinical trials. Our society is in the midst of a paradigm shift that began with the discovery of viruses as dangerous infectious agents and will end with the use of viruses to cure disease and regenerate tissues.

On January 19, 1989, the director of the National Institutes of Health (NIH), Dr. James A. Wyngaarden, approved the first clinical protocol to insert a foreign gene into the immune cells of persons with cancer (Roberts, 1989). On September 14, 1990, W. French Anderson and his colleagues at the NIH performed the first approved gene therapy procedure on a four-year-old girl born with severe combined immunodeficiency (SCID) (Anderson, 1990). Despite the viral horror stories written by the popular media, this initial trial was largely a success, and the most recent report on this individual in 2004 noted that she is thriving as an 18-year-old teenager in suburban Cleveland (Springen, 2004). Over the next ten years, 300 clinical gene therapy trials were performed on about 3000 individuals (McKie, 2000). The field was then blackened with the death of an 18-year-old male four days after the introduction of 38 trillion particles of recombinant adenovirus into his liver (Somia and Verma, 2000). Despite this tragedy, we continue to move forward because of the great promise of novel genetic treatments that, when perfected, will likely outshine current methods, such as protein therapy or pharmacotherapeutics, for treatment of many diseases and defects.

We are now nearing the 20-year mark since the first gene therapy trial. Though success has been limited, the future still seems overwhelmingly promising, and we are steadily approaching an acceptable safety record. This review will explore non-viral and viral methods available for transgene introduction as well as their current and potential applications for craniofacial regeneration and therapy, with emphasis on future development and design.

Though this review will focus mostly on viral methods of gene delivery, it is essential to recognize that many advances have been made in the field of non-viral gene therapy. Polymeric gene delivery is desired because of its relative safety, low immunogenicity and toxicity, ease of administration and manufacture, and lack of DNA insert size limitation (Park et al., 2006). The main disadvantage is insufficient gene transfer efficiency due to the need for post-uptake endosomal escape and nuclear translocation of the DNA complex (Park et al., 2006). In this respect, clinical efficiency and specificity standards have not yet been met.

The main strategy for most synthetic polymer delivery systems is to generate cationic polymers to interact electrostatically with and neutralize negatively charged DNA (Park et al., 2006). This facilitates properties such as protection from DNAses. If a net positive charge is maintained, the polymer/DNA complex can adhere to the cell surface glycocalyx and be internalized by endocytic mechanisms. Unfortunately, the use of endocytic uptake from the external environment perpetuates the need for endocytic escape into the cytosol. This challenge in the polymeric gene delivery field has been addressed by multiple strategies, including incorporation of fusogenic peptides for endosomal membrane binding and disruption (Cho et al., 2003) and by balancing a hydrophobic cholesterol group with hydrophilic polymers to enhance escape (Mahato et al., 2001).

One of the first polymers recognized for its ability to form nanoparticulate polyelectrolyte complexes with DNA was Poly L-lysine (PLL) (Laemmli, 1975). Unfortunately, this cationic material was found to have high cytotoxicity (Choi et al., 1998) and a tendency to aggregate and precipitate (Liu et al., 2001). The solution to this dilemma was found in the form of the flexible, water-soluble polymer polyethylene glycol (PEG). Covalent coupling of PEG, or PEGylation, of a target molecule such as PLL limits its cytotoxicity and non-specific protein adsorption (Choi et al., 1998). This strategy has also been used with polyethyleneimine (PEI), a cationic gene carrier with superior transfection efficiency and unique buffering properties (Boussif et al., 1995), similarly to reduce the extent of inter-particular aggregation (Mishra et al., 2004; Quick and Anseth, 2004).

In addition to improving the bio-properties of PLL and PEI, PEGylated polymers can be conjugated to specific targeting moieties, such as sugars, antibodies, peptides, and folate (Lee and Kim, 2005). For example, peptide conjugation of the apoB-100 fragment of low-density lipoprotein can increase transfection efficiency in bovine aorta and smooth-muscle cells 150- to 180-fold (Nah et al., 2002), and RGD peptides can allow for increased selection of endothelial cells (Kim et al., 2005). To summarize, synthetic PEGylated polymers such as PLL and PEI are promising gene delivery molecules. Future study in this field is focused on biodegradable polycations such as poly(-amino ester), poly(2-aminoethyl propylene phosphate), and degradable PEI to decrease cytotoxicity and increase transfection efficiency (Akinc et al., 2003).

The natural polymer family contains materials such as cyclodextrin, chitosan, collagen, gelatin, and alginate. When compared with synthetic materials, natural polymers have the advantage of innate environmental responsiveness and the ability to be degraded and remodeled by cell-secreted enzymes. They are non-toxic at both low and high concentrations, are readily incorporated into oral or bolus matrix delivery systems, and can serve as tissue engineering scaffolds (Dang and Leong, 2006). The simplicity of oral delivery and mucoadhesive properties of materials such as chitosan make it an interesting potential polymer for gene delivery and vaccination (Roy et al., 1999). The transfection efficiency of natural polymers such as cyclodextrin, though significantly less than that of virus, is similar to that of PEI and lipofectamine (Gonzalez et al., 1999). Thus, while natural polymers benefit from degradation and remodeling, they still face significant transfection issues due to the requirement for endosomal escape. However, this strategy has been successfully used to increase bone regeneration with polymer gene activated matrix containing DNA encoding parathyroid hormone (Bonadio et al., 1999; Chen et al., 2003)

Viruses have undergone millions of years of evolution and are a species-conserved way of introducing DNA to cells (Dewannieux et al., 2006). Scientists are now attempting to fine-tune these gene delivery vehicles for treatment of human disease and defects. Regardless of method selection, there are three universal requirements for viral gene therapy vectors. First, the delivery system must be safe and immunologically inert. Second, it must protect the genetic material from degradation. Third, the vector must encode an effective therapeutic gene that has sustained expression at a defined target site. For true commercial application, the packaged vector must also be easily produced and processed and have a reasonable shelf-life. As we near the 20-year mark from the first human gene therapy clinical trial, significant advances have been made in satisfying these three requirements. However, new objectivessuch as tissue-specific targeting, site-specific chromosomal integration, and controlled infection of both dividing and non-dividing cellshave emerged. Though negative publicity has attached a significant stigma to viral gene therapy, it is indeed the most efficient method of gene transfer, and basic research and clinical trials are rapidly moving to overturn the safety concerns.

Our society is in the midst of a paradigm shift that began with the discovery of viruses as dangerous infectious agents and will end with the use of viruses to cure disease and regenerate tissues. However, safety concerns still limit the universal acceptance of this strategy. These concerns include the accidental generation of replication competent viruses during vector production and the packaging or mobilization of the engineered vector by endogenous retroviruses present in the human genome (Connolly, 2002). Either of these could lead to horizontal dissemination of new viruses from gene therapy patients. Localized concerns include random insertion or mutagenesis of the vector leading to cancer, or germ cell alteration resulting in vertical inheritance of the acquired gene (Connolly, 2002). The need for controlled genome integration hit home when two of the 11 persons treated for X-SCID with retrovirally transduced stem cells developed leukemia due to insertion of the transgene near the oncogenic gene LMO2 (Kaiser, 2003). Site-specific chromosomal integration, conditional expression of the transgene only in target cells, and the use of self-inactivating (SIN) retroviral vectors have been proposed (Yu et al., 1986) and may significantly improve the safety of viral therapy. The following sections will review the use of viral vectors for in vivo therapy, emphasizing the construction and advantages of different viruses.

Before we can successfully manipulate retroviral vectors, the composition of their genome must be thoroughly understood. Since the discovery of retroviruses in 1910, when Peyton Rous induced malignancy in chickens by the injection of cell-free filtrates from muscle tumor (VanEpps, 2005), we have gained much insight into their mechanism of action. Three main classes of recombinant retroviruses are used as tools in gene delivery: -retroviruses, lentiviruses, and spumaviruses (Chang and Sadelain, 2007). Despite their negative press, exogenous retroviruses have been used in many biological studies and facilitated the discovery of proto-oncogenes (Martin, 2004), the manipulation and investigation of intracellular pathways, and successful ex vivo treatment of persons with hemophilia and SCID (Sumimoto and Kawakami, 2007; Chu et al., 2008; Scheller et al., 2008). Retroviruses are 80- to 100-nm enveloped viruses that contain linear, non-segmented, single-stranded RNA. Retroviruses are naturally self-replicating for viral assembly and re-infection (Kurian et al., 2000). Reverse transcription allows for the generation of double-stranded DNA from the transduced 7- to 12-kBp RNA and subsequent insertion into the genome. Exogenous retroviruses can be subdivided into simple and complex categories based on the composition of their RNA vector. Simple vectors contain three basic genesgag, pol, and envwhich are necessary for viral replication and must be removed prior to gene therapy (Buchschacher, 2001) (). Identical long terminal repeats (LTRs) are present at each end of the retroviral genome. The LTRs contain promoter, enhancer, and integration sequences which facilitate interaction with attachment sites via integrase (Engelman, 1999). Complex retroviruses contain up to 15 additional accessory genes, such as tat, the transcriptional transactivator for HIV-1, vif, rev, nef, etc. (Frankel and Young, 1998).

Retroviral vector development for increased efficiency and targeting. (A) Structure of a simple retroviral genome containing coding sequences for gag, pro, pol, and env for replication. (B) Structure of a simple -retroviral gene therapy vector …

The use of retrovirus as a gene delivery system necessitates re-engineering of the viral genome to block autonomous replication while maintaining integration efficiency. This is accomplished via the maintenance of cis-acting and removal of trans-acting factors. Five essential components for successful viral gene expression by any LTR-driven -retroviral vector include dual-LTRs, att site, primer binding site, signal psi, and the polypurine tract (Zhang and Godbey, 2006) (). The polypurine tract aids in transport of the pre-integration complex to the nucleus and allows for internal initiation of second-strand DNA synthesis (Zennou et al., 2000). Most -retroviral vectors rely on their LTRs to drive robust and ubiquitous transgene expression. Replacement of these with site-specific constitutive promoters is currently limited by expression strength and promoter silencing, but remains an active area of research that could allow for customization of transgene expression level and location. Additional vector design strategies to enhance gene expression and reduce silencing include: deletion of silencing elements (Zufferey et al., 1998), incorporation of robust promoters such as U3 or PGK (Chang and Sadelain, 2007), incorporation of woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) to enhance mRNA transcript stability (Loeb et al., 2002), incorporation of scaffold or matrix attachment regions for anchorage of chromatin with stabilization of chromosomal loops (Agarwal et al., 1998), and use of insulators such as the chicken -globin locus control region to limit position effect variegation (West et al., 2002) (). Expression in bacterial plasmid form can be used for easy amplification and incorporation of drug resistance or response genes to facilitate selection ex vivo or expression in vivo (Delviks and Pathak, 1999; Jaalouk et al., 2000). Addition of the gene of interest or resistance gene under the control of a tissue-specific promoter results in a dual-promoter vector designed to enhance selection and integration. However, simultaneous use of two promoters can result in significantly reduced expression of both due to promoter interference (Apperley et al., 1991). SIN vectors which develop a defective promoter in the viral LTR have been used to circumvent this effect (Buchschacher, 2001) (). Understanding and engineering of these vectors is rapidly advancing. For example, it has been shown that ex vivo transduction of hematopoietic stem cells can be improved through control of cell-cycle stage during virus delivery (Korin and Zack, 1998) and the use of proteosome inhibitors (Goff, 2004).

Retroviruses require genome integration of their vector to function, and most, excluding lentiviruses such as HIV-1, are able to infect only dividing cells (Lewis and Emerman, 1994). Stable integration of retroviral vectors is known to occur near expressed genes and appears to be non-random (Mitchell et al., 2004). This allows for long-term expression of the transgene and makes retroviruses the vector of choice for ex vivo and in vivo transduction of highly replicative populations such as tumor cells and hematopoietic cells for treatment of chronic disease and genetic deficiency (Somia and Verma, 2000). Indeed, LTR-driven -retroviral vectors have been used in over 45 ex vivo clinical trials to treat diseases such as hemophilia, SCID, and leukemia (Kohn et al., 2003; NIH, 2008b). To advance gene therapy with retroviral vectors, increased transduction efficiency and gene expression, site-specific chromosomal integration, and cell-specific targeting are necessary. Ex vivo or in vivo -retroviral transduction of rapidly dividing cells at sites of wound healing and new bone synthesis may be used in the future to enhance craniofacial tissue regeneration. Expansion of this field to include lentiviral vectors targeting non-dividing cells could allow for the long-term restoration of non-functional salivary gland tissue or repair of quiescent periodontal defects.

Adenoviridae were initially isolated by Wallace Rowe in 1953 from adenoid explants as the virus of the common cold (Rowe et al., 1957; Ginsberg, 1999). They have since become attractive tools for gene therapy, given that their infection is generally self-limiting and non-fatal (Zhang and Godbey, 2006). Adenoviruses are the largest non-enveloped virus and contain linear, double-stranded DNA. Over 50 serotypes have been identified, but the most common in nature and in adenoviral gene therapy are group C human serotypes 2 and 5 (Barnett et al., 2002). The icosahedral adenoviral capsid is made up of hexon and penton proteins, knobbed fibers, and stabilizing minor cement proteins. These surround the core proteins and large 36-kBp adenoviral genome (Verma and Somia, 1997). The ends of the genome have inverted terminal repeats which flank a coding region capable of encoding more than 30 viral genes (Zhang and Godbey, 2006). These genes are termed early or late, depending on their temporal expression. Early genes function as regulatory proteins for viral replication, while late genes encode structural proteins for new virus assembly (Zhang and Godbey, 2006). Entry of adenovirus into the cell occurs when penton base proteins bind integrins for clathrin-mediated endocytosis. Subsequent disruption of the endosome and capsid allows for viral core entry into the nucleus (Russell, 2000). Initiation of the immediate early infection phase activates transcription of the E1A gene, a trans-acting transcriptional regulatory factor that is required for early gene activation (E1B, E2A, E2B, E3, E4, viron proteins) (Russell, 2000). The final late infection phase activates genes L1 to L5 through complex splicing; viral particles which accumulate in the nucleus are then released via cell lysis (Zhang and Godbey, 2006).

During the engineering of adenoviral vectors for gene delivery, up to 30 kbp of the 36-kbp genome can be replaced with foreign DNA (Smith, 1995). Multiple strategies have been used to produce replication-defective, transforming adenoviral vectors. In first-generation adenoviral vectors, E1 and E3 genes are deleted to allow for a 6.5-kbp insertion. However, cell-line endogenous expression of E1 can lead to E2 expression and viral replication at low levels (Russell, 2000). Other first-generation vectors have used deletion of E2 and E4 regions to allow for an insert of greater than 6.5 kbp (Lusky et al., 1998). These vectors are impaired by limited expression and a robust inflammatory response (Khan et al., 2003). Second-generation gutless vectors appear to be the most promising. Gutless vectors retain only the inverted terminal repeats and packaging sequence around the transgene (Russell, 2000). This results in prolonged transgene expression, increased insert size allowance, and reduced immune response (Fleury et al., 2004). Studies have shown that adenoviral gene expression occurs via episome formation, and only 1 in 1000 infectious units can integrate into the genome (Tenenbaum et al., 2003). Though this decreases the risk of insertional mutagenesis, it also limits adenoviral application to high-level transient transgene expression, because the gene is often lost 5 to 20 days post-transduction (Dai et al., 1995). Adenoviruses have the significant advantage of being able to infect both dividing and non-dividing cells (Verma and Somia, 1997). This makes them specially suited for applications involving brain, eye, lung, pancreas, hepatocytes, neurons, and monocytes (Blomer et al., 1997; Kafri et al., 1997). PEGylation and expression of targeting ligands on the viral capsid are being investigated to decrease the immune response and enhance targeting of adenoviral vectors (Eto et al., 2008). A clinical trial with adenovirus to repair salivary gland tissue post-radiation therapy is ongoing (Baum et al., 2006; NIH, 2008b).

Adeno-associated virus (AAV) is a parvovirus of the Dependovirus genus that was discovered in 1965 as a co-infecting agent of adenovirus preparations (Carter, 2005). The first infectious clone of AAV serotype 2 to be used for human gene therapy was generated in 1982 (Samulski et al., 1982). Since that time, AAV serotypes 1-12 and over 100 AAV variants have been isolated (Wu et al., 2006). AAV is a non-enveloped DNA virus with a 22-nm icosahedral capsid containing a 4.7-kBp linear single-stranded DNA genome. Coding capacity is limited to 4.5 kBp, but may be extended by splitting the sequence between 2 viruses that can later concatamerize after transduction (Nakai et al., 2000). The genome contains 2 unique open reading frames (ORFs) which encode 4 replication proteins and 3 capsid proteins, respectively (Ding et al., 2005). Inverted GC-rich self-complementary terminal repeats flank the ORFs and are the only cis-acting factors required for genome replication and packaging (Ding et al., 2005). Two ORF-encoded trans-acting proteins required for viral replication are rep, which controls viral replication and integration, and cap, which encodes structural components of the capsid. Though site-specific integration on chromosome 19 occurs if rep is maintained (Kotin et al., 1990), it is generally removed from rAAV-engineered vectors. Advantages of AAVs include low immunogenicity, lack of pathogenicity, a wide range of infectivity with potential cell-/tissue-specific targeting, and the ability to establish long-term latent transgene expression in both dividing and non-dividing cells.

AAVs are naturally replication-deficient and require a helper virus for replication and dissemination (Zhang and Godbey, 2006). Self-limiting infection, coupled with their ability to stably infect dividing and non-dividing cells, makes them an excellent target for in vivo gene therapy and craniofacial applications. It is generally accepted that AAV vectors persist as non-integrated circular episomal concatemers, and research shows an integration frequency of less than 1 in 30 million particles in studies of AAV delivery to muscle in rabbits (Schnepp et al., 2003; Schultz and Chamberlain, 2008). Infection occurs through binding of viral proteins to charged heparin sulfate proteoglycans (Summerford and Samulski, 1998) and is potentially enhanced by interactions with alpha-V-beta-5 integrins (Summerford et al., 1999) and human fibroblast growth factor receptor-1 (Qing et al., 1999). After clathrin-mediated endocytosis, endosomal escape, and nuclear translocation, AAV can produce latent long-term infection via episome formation in which the transgene reaches maximum expression levels after an incubation period of 4 to 8 wks and remains stable for up to 2-3 yrs in animal models (Thomas et al., 2004; Manno et al., 2006). Though it is becoming less of an issue, one of the challenges facing viral engineers is the large-scale amplification of AAVs. Baculovirus expression systems for rAAV2 vector production in SF9 cells show promise for large-scale production (Urabe et al., 2002). However, current clinical trials are limited by their reliance on transient production systems and still require complete elimination of helper virus during production (Kay et al., 2000).

The primary goal for rAAV engineering is to improve transduction efficiency to decrease vector loading while increasing target specificity. An initial successful effort to improve transduction was a switch from single-strand to self-complementary recombinant AAV vectors, to bypass the rate-limiting second-strand DNA synthesis step (McCarty et al., 2001). Because of high variation among capsids, AAV vectors have inherent tissue-targeting abilities that can be enhanced with capsid re-engineering. For example, AAV6 demonstrates increased transduction efficiency in skeletal muscle (Gao et al., 2002), and AAV4 shows preference for the CNS (Davidson et al., 2000). DNA shuffling and cloning technologies are currently being used to generate extensive libraries of recombinant AAVs that display diverse tissue specificity and potential to evade host-neutralizing antibodies (Perabo et al., 2006; Li et al., 2008). The crystal structure of the AAV2 capsid was solved in 2002 (Xie et al., 2002). AAV virons have icosahedral capsids made of 60 copies of VP1, VP2, and VP3 proteins encoded by the second genomic ORF in a variable predicted ratio of 1:1:18 (Muzyczka and Warrington, 2005). VP1 and VP2 are variable between AAV serotypes (Wu et al., 2006). Mosaic vectors (capsid structure derived from subunits of different serotypes) or chimeric vectors (capsid proteins modified by domain or amino acid swapping between serotypes) have been generated through trans-capsidation or marker-rescue/domain-swapping (Wu et al., 2006) () to enable the infection of tissues refractory to transduction by naturally occurring AAV vectors or to limit AAV infection to specific tissues (Wu et al., 2006). Insertion of peptide ligands, conjugate-based targeting, and presentation of large protein ligands on the AAV capsid are additional strategies that have been used to enhance targeting and transduction of rAAVs (Muzyczka and Warrington, 2005) (). Insertion sites for peptide-encoding DNA sequences are limited to maintain infectivity of the viron. A 14-residue core RGD peptide motif insertion is possible in VP3 at residues 261, 381, 447, 459, 573, 584, 587, and 588 (Girod et al., 1999; Shi and Bartlett, 2003) (). Integrin-RGD interactions could be exploited by craniofacial tissue engineers to enhance infection of endothelial cells and localization of rAAV to matrix-laden sites such as bone and tooth.

AAV capsid engineering for enhanced transduction and tissue-specific targeting. (A) Mosaic vectors (capsid structure derived from subunits of different serotypes) or chimeric vectors (capsid proteins modified by domain or amino acid swapping between serotypes) …

There are three main strategies for gene delivery: in vivo, in vitro, and ex vivo. Though the most direct method is in vivo injection, this approach lacks the improved patient safety of in vitro and ex vivo methods. Systemic delivery is desirable if the target tissue is not directly accessible. However, this method often results in low specificity of gene expression, risks of toxicity due to the high vector concentration required, and potential damage to the function of healthy tissues (Zhang and Godbey, 2006). Alternatively, matrix-based delivery allows for tissue-specific gene delivery, higher localized loading of DNA or virus, and increased control over the structural microenvironment (Dang and Leong, 2006). Thus far, human in vivo clinical trials have introduced adenovirus, AAV, retrovirus, and herpes simplex virus by intravenous (IV) injection, intra-tissue injection, or lung aerosol (Kemeny et al., 2006). In contrast, ex vivo trials have focused on stable retroviral transduction of rapidly dividing populations such as CD8+ T-cells, hematopoietic stem cells, hepatocytes, and fibroblasts, followed by IV or local re-introduction. At the time of this publication, a search of the NIH Genetic Modification Clinical Research Information System (GeMCRIS) revealed 908 total gene therapy clinical trial entries in the database (NIH, 2008a). At, a search for interventions with gene transfer OR gene therapy returned 174 studies, of which 145 are viral-based, with 84 active, 48 completed, and 7 terminated. This cross-section of results translates to 1605 persons who have participated in this subset of completed gene therapy trials and nearly 5000 total active or anticipated participants, based on each studys documented enrollment since 1990. The following sections will briefly review the progress of gene therapy since 1990.

Gene therapy is specially suited for long-term delivery of a transgene to persons with a single genetic deficiency that is not amenable to protein or pharmacokinetic therapy. This was the premise of the first successful gene therapy clinical trials that inserted genes ex vivo into CD34+ cells to treat persons with SCID (Anderson, 1990; Blaese et al., 1993). Amazingly, persistence of the adenosine deaminase (ADA) transgene was noted in peripheral blood leukocytes 12 yrs post-therapy without adverse events (Muul et al., 2003). Since 1990, clinical treatment of genetic diseasesincluding cystic fibrosis, hemophilia, Leber congenital amaurosis, muscular dystrophy, ornithine transcarbamylase deficiency, Pompe disease, and Gauchers diseasehas been attempted, with promising documented success (Aiuti et al., 2007; Alexander et al., 2007). Following the SCID trials, treatment of cystic fibrosis by re-introduction of the cystic fibrosis transmembrane regulator (CFTR) chloride ion channel to lung epithelial cells was highly targeted and was the first use of rAAV in humans (Flotte et al., 2003). However, like many other in vivo and ex vivo clinical trials, transduction efficiency was generally insufficient to improve clinical parameters significantly. Apart from SCID, the most promising documented results for genetic deficiency correction have been the replacement of factor IX (F-IX) in hemophilia. Studies by Avigen Inc. have examined rAAV2-mediated F-IX delivery to the liver. In dogs, therapeutic levels of F-IX were achieved for multiple years following vector treatment (Manno et al., 2006). In humans, delivery of rAAV2.F-IX through the hepatic artery achieved therapeutic levels of F-IX expression for approximately 8 wks (Aiuti et al., 2007). It appears that cell-mediated immunity to the rAAV2 capsid limits expression in humans. Thus, immunomodulation and capsid engineering may make F-IX therapy a near-future reality (Krebsbach et al., 2003; Manno et al., 2006). Gene therapy is also highly desired for the treatment of neurologic and other chronic disease. Clinical trials have been implemented and/or completed for the treatment of HIV/AIDS, arthritis, angina pectoris, solid tumors, Parkinsons disease, Huntingtons disease, Alzheimers disease, Batten disease, Canavan disease, and familial hypercholesterolemia (Aiuti et al., 2007; Alexander et al., 2007; NIH, 2008a,b). Despite the many hurdles, most clinical trials are progressing steadily, with treatments for angina pectoris (Henry et al., 2007), prostate cancer (Freytag et al., 2007), non-small-cell lung cancer, and head and neck cancer now entering phase III clinical trials (NIH, 2008b).

More than 85% of the United States population requires repair or replacement of a craniofacial structure, including bone, tooth, temporomandibular joint, salivary gland, and mucosa. Regeneration of oral and craniofacial tissues presents a formidable challenge that requires synthesis of basic science, clinical science, and engineering technology. Identification of appropriate scaffolds, cell sources, and spatial and temporal signals are necessary to optimize development of a single tissue, hybrid organs consisting of multiple tissues, or tissue interface. In contrast to traditional replacement gene therapy, craniofacial regeneration via gene therapy seeks to use genetic vectors as supplemental building blocks for tissue growth and repair. Synergistic combination of viral gene therapy with craniofacial tissue engineering will significantly enhance our ability to repair and regenerate tissues in vivo.

Though the treatment of HNSCC does not directly fall in the category of craniofacial regeneration, it is the most well-developed use of gene therapy in the craniofacial region. There are three main strategies to target any solid tumor with gene therapy. First, immunomodulatory therapy seeks to increase the visibility of the tumor cells to the immune system in vivo or to modify the effector cells ex vivo to increase targeting of the tumor via the introduction of specific gene expression. In 2007, the dendric cell vaccine Provenge was deemed safe and preliminarily approved by the FDA advisory panel in a 13 to 4 vote for the treatment of prostate cancer. However, it was later denied final approval and is currently being re-evaluated (Moyad, 2007). Second, oncolytic viruses have been developed that can selectively target, multiply in, and destroy cancer cells (Dambach et al., 2006). A phase II clinical trial of OncoVex (GM-CSF), with combined chemoradiotherapy in locally advanced head and neck cancers, is ongoing (Aiuti et al., 2007). In addition, the H101 oncolytic adenovirus has undergone phase I-III clinical trials for treating head and neck cancer and is now approved for use in China (Yu and Fang, 2007). Third, suicide genes such as herpes simplex thymidine kinase can be introduced to cancer cells to increase their susceptibility to anti-viral drugs such as acyclovir (Niculescu-Duvaz and Springer, 2005). As mentioned above, application of these methods for treatment of various cancers comprises the majority of the current phase III clinical gene therapy trials (NIH, 2008b). Additional strategies of interest for specific targeting of HNSCC include local viral introduction of genes encoding p53 (Clayman et al., 1999; Yoo et al., 2004), endostatin (Lin et al., 2007), and non-viral IL-2/IL-12 (OMalley et al., 2005).

Animal-model-based gene therapy and engineering of individual craniofacial structures such as bone and cartilage have firmly established a productive relationship, and novel approaches to regeneration of complex mineralized tissues such as tooth (Nakashima et al., 2006) and TMJ (Rabie et al., 2007) are just beginning to emerge. Clinical protein delivery of PDGF-B or bone morphogenetic proteins (BMPs) at periodontal defect sites is well-known to enhance repair and healing of bone and gingiva (Kaigler et al., 2006). Gene delivery can allow for localized sustained protein expression at therapeutic levels and can overcome recombinant protein delivery issues such as cost, half-life, supra-physiologic dosing, and poor retention. In support of this, studies have shown that use of adenovirus expressing PDGF-B for treatment of periodontal defects demonstrates better results than continuous protein therapy (Jin et al., 2004; Franceschi, 2005) (). Adenoviral-, retroviral-, and AAV-mediated delivery of osteogenic genes has been demonstrated to enhance fracture repair and intramembranous or endochondral bone formation in vivo in animal models (). To meet clinical needs, gene delivery must be safe, simple, and cost-effective. Thus, focus on in vivo strategies which avoid primary cell isolation and long-term culture is ideal. An expedited ex vivo bone regeneration strategy has recently been proposed in which explants of adipose tissue or muscle directly transduced with Ad.BMP-2 without culture can be re-implanted at defect sites to enhance regeneration of critical-sized rat femoral defects (Betz et al., 2008) (). In addition, studies to release virus directly from biomaterials have been effective for bone regeneration in animal models (Hu et al., 2007)

Virally Transduced Genes for Regeneration of Craniofacial Tissues

Gene therapy for bone regeneration. (A) An expedited ex vivo bone regeneration strategy has recently been proposed in which explants of adipose tissue or muscle can be directly transduced with Ad.BMP-2 without culture. This has shown …

Inducible vector systems, use of rAAV, and transduction of novel osteogenic factors have outstanding potential for mineralized tissue regeneration. In addition to vector design and capsid engineering for cell-specific transduction, we must now consider the use of systemic drug-inducible vector components. For example, an early study using a retroviral vector demonstrated dexamethasone-inducible GFP expression from transduced BMSCs in vitro (Jaalouk et al., 2000). Researchers have gone on to explore doxycycline-inducible tetON promoter systems. In these systems, selective induction of BMP-2 or BMP-4 expression achieved by administration of oral doxycycline can allow for localized induction of bone formation only at vector-containing sites in vivo (Gafni et al., 2004; Peng et al., 2004) (). The field of rAAV-mediated bone repair is rapidly advancing and promises superior safety, tissue targeting, and high in vivo transduction efficiency of non-dividing cells. In the past 5 years, proof-of-principle studies have been completed and have shown positive results for AAV transduction of bone-forming cells and enhanced healing of osseous defects from in vivo application of rAAV expressing constitutively active activin receptor-like kinase-2 (caAlk2), VEGF/RANKL, and ex vivo BMP-7 (Kang et al., 2007; Ulrich-Vinther, 2007) (). The use of caAlk2, a receptor that mediates BMP signaling, is emerging as an interesting gene therapy target, because of its low required therapeutic expression level and inability to be blocked by native BMP antagonist noggin and chordin (Zhang et al., 2003; Koefoed et al., 2005; Ulrich-Vinther, 2007).

Successful engineering of teeth and the TMJ is challenging and requires the generation of functional interfaces. The introduction of BMPs in vivo to exposed pulp tissue has been proposed as a novel strategy for odontoblast transduction to enhance dentin regeneration and repair (Nakashima et al., 2006). However, gene therapy has not yet been applied to the field of total tooth engineering (Young et al., 2005; Hu et al., 2006). Engineering of the TMJ requires the creation of functional bone and cartilage with an appropriate transition zone. Investigators have generated such osteochondral grafts by seeding differentiated pig chondrocytes and Ad.BMP7-transduced human gingival fibroblasts onto biphasic PLLA/hydroxyapatite composite scaffolds and implanting them subcutaneously into N: Nih-bg-nu-xid immunocompromised mice (Schek et al., 2004, 2005). Marrow-containing vascularized bone, mature cartilage, and a defined mineralized interface can be generated within 4 wks of implantation (Schek et al., 2004, 2005). A second approach to TMJ repair is the in vivo introduction of therapeutic genes to the mandibular condyle. Recent work has demonstrated successful rAAV2-mediated transduction of VEGF to condylar tissue in vivo that subsequently enhanced mandibular condylar growth (Rabie et al., 2007) (). These pioneering studies provide proof-of-principle evidence for the fabrication of a physiologic osteochondral graft and direct TMJ transduction that may be developed to treat persons with TMJ disorders or developmental deformities.

Loss of salivary gland function can result as a pharmacologic side-effect, from radiation therapy, or as a consequence of autoimmune diseases such as Sjgrens syndrome. In addition to direct repair of non-functional glandular tissue, researchers are working to develop an engineered salivary gland substitute that could be implanted in place of the parotid gland (Aframian and Palmon, 2008). Unlike acinar cells, ductal epithelial cells are incapable of fluid secretion. Because researchers have been unable to isolate and expand acinar cells in vitro, identification and localization of membrane proteins required for ionic gradient formation and fluid flow in acinar cells have informed efforts to modify ductal cell populations by gene transfer. Acinar cells require 4 membrane proteins to generate an osmotic gradient for unidirectional fluid movement: (1) the N+K+-ATPase, used to maintain membrane potential; (2) a Ca2+-activated K+ channel; (3) the secretory isoform of the Na+/K+/2Cl- co-transporter; and (4) the apical membrane-bound Ca2+-activated Cl- channel (Melvin et al., 2005; Aframian and Palmon, 2008). Salivation occurs in response to agonists that generate an increase in intracellular Ca2+ concentration and is facilitated by osmotic gradient-directed fluid movement through water channels in the apical membrane, known as aquaporins (AQP) (Melvin et al., 2005). It is now recognized that isolated ductal epithelial cells lack expression of AQP and, as such, cannot mediate fluid movement (Tran et al., 2006). Re-introduction of transient AQP expression by adenoviral transduction has been successful in rhesus monkey parotid duct cells in vitro (Tran et al., 2005) and rat and mini-pig salivary gland tissue in vivo (Baum et al., 2006). Indeed, attempts to restore salivary flow by in vivo transduction of adenovirus encoding AQP1 into remaining glandular tissue of persons treated with radiation for head and neck cancer is the first human craniofacial repair gene therapy clinical trial and is currently ongoing (Baum et al., 2006; NIH, 2008b).

Engineering of skin and mucosal equivalents is essential for the esthetic reconstruction of individuals disfigured by trauma, resective surgery, or severe burns. Skin is composed of layered dermis and epidermis in a configuration that must be preserved for optimum regeneration. The first attempts to repair damaged skin and mucosa with an engineered graft did not occur until the 1980s (Madden et al., 1986). Skin with both dermal and epidermal components, such as DermagraftTM (Purdue et al., 1997) and ApligrafTM, used for coverage of burns and acute wounds (Eaglstein et al., 1995), was the first FDA-approved tissue-engineered construct that has been put into clinical practice. Clinically, a product known as gene-activated matrix (GAM) has been developed as an enhanced skin graft substitute. GAM for wound-specific delivery of adenovirus vector encoding PDGF-B to improve healing of diabetic ulcers is currently in Phase II clinical trials (Gu et al., 2004; NIH, 2008b). It is reasonably expected that these developments could be expanded to enhance wound healing and tissue repair in the craniofacial region (Jin et al., 2004).

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Exit 390 at 16B (E. Henrietta Rd.)

Turn left at the exit. Make a Right on Westfall Rd.

Pass South Clinton and make a Left at Lac De Ville Blvd.

Were on the left side of the road past homes opposite pond.

COMING FROM THE EAST Take 490 to 590 South and exit at Winton Rd.

Turn Right at exit. Then turn Left on Westfall Rd.

The second light is Lac De Ville Blvd. Turn Right at this light.

Were on the left side of the road past homes opposite pond.

COMING FROM THE SOUTH Take 390 North to 590 and exit at Winton Rd. Turn Left at exit and another Left at Westfall Rd.

The second light is Lac De Ville Blvd. Turn Right at this light.

Were on the left side of the road past homes opposite pond.

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