Anyone who has left youth behind them knows that bumps and scrapes don’t heal as fast as they used to. But that could change with researchers at the Stem Cell Program at Boston Children’s Hospital finding a way to regrow hair, cartilage, bone, skin and other soft tissues in a mouse by reactivating a dormant gene called Lin28a. The discovery could lead to new treatments that provide adults with the regenerative powers they possessed when very young.
Lin28 is a gene that is abundant in embryonic stem cells and which functions in all organisms. It is thought to regulate the self-renewal of stem cells with the researchers finding that by promoting the production of certain enzymes in mitochondria, it enhances the metabolism of these cellular power plants that found in most of the cells of living organisms. In this way, Lin28 helps generate the energy needed to stimulate the growth of new tissues.
“We already know that accumulated defects in mitochondrial metabolism can lead to aging in many cells and tissues,” says Shyh-Chang Ng. “We are showing the converse – that enhancement of mitochondrial metabolism can boost tissue repair and regeneration, recapturing the remarkable repair capacity of juvenile animals.”
The combination of the two technologies could be an important step toward the development of useful, practical telemedicine.
VIPAAR (Virtual Interactive Presence in Augmented Reality) is commercializing a UAB-developed technology that provides real-time, two-way, interactive video conferencing.
In is now quite clear that aging is not a simple phenomenon and it will not be overcome by using simple approaches. We need to increase the complexity and sophistication of our efforts in order to be in a better position to develop strategies against it. For this reason, I set up the ELPIS Foundation for Indefinite Lifespans (www.elpisfil.org) which is a scientific research organisation aiming to study aging from a complex evolutionary perspective.
The foundation’s research methodology is based mainly upon the ELPIS hypothesis (www.elpistheory.info). The initials stand for ‘Extreme Lifespans through Perpetual –equalising Interventions’. I developed this hypothesis in 2010 whilst trying to examine the reason behind the presence of aging. It was clear that aging is not an essential component of our evolutionary development, and if we find ways to study why nature has developed it, we may then be able to eradicate it. Currently, the chances of us dying from aging are heavily against us. By developing suitable interventions, we may be able to equalise the odds against us dying (i.e. remove aging as a cause of death).
Our method is different from most existing approaches aiming to eliminate aging. We are mainly interested in the ‘connection-approach’ and not so much in the ‘component-approach’. We believe that it is important to study how the different components of the organism are interconnected and regulated, rather than just repair the individual components. It is the ‘why aging happens’ rather than the ‘how it happens’ that interests us most. In order to make this clear let me mention an analogy with poliomyelitis.
Polio *How it happens? There is inflammation and necrosis leading to damage of motor neurons and, ultimately, muscle weakness and paralysis * Why it happens? Because the poliovirus causes it
Aging * How it happens? There is cellular and molecular damage through oxidation and glycation, as well as damage to mitochondria, DNA etc. * Why it happens? Because evolution has selected reproduction (and thus aging) as a mechanism for maximising the use of thermodynamical resources, and so ensure the survival of the species.
In this analogy, the obvious cure for polio is to somehow eradicate the poliovirus itself, and not just keep repairing the already damaged motor neurons. And in the case of aging, the best tactic is to somehow change the reason why aging happens, instead of just keep repairing already existing damage.
Attempts such as SENS and similar, aim to repairing existing damage, were as we aim primarily to eliminate the evolutionary reasons behind aging in the first place. This is not to say that we are not at all interested in damage repair. In fact, one of our main projects deals with the repair problem. But, overall we want to explore the evolution of aging and not its secondary effects.
We see aging as a specific and well-defined process. Our aim is unambiguous: we seek to eliminate this particular process. By eliminating aging we will have a life without age-related disease and degeneration, and a lifespan without a predetermined end. We do not seek immortality. In order to be immortal, one has to totally and permanently eliminate all causes of death (not just reduce their incidence). We seek to eliminate aging as one of the causes of death. People will still die from any other cause. In this case, our lifespan would be ‘indefinite’ because the current absolute limit of around 110–120 years will be lifted. There would not be a pre-defined limit; therefore the lifespan would be indefinite. It will not be infinite. This distinction is crucial because it clarifies any ambiguity and vagueness in the terminology. We do not seek eternal youth. We merely concentrate on the process of aging as one of the many other causes of death, the same as other researchers concentrate on the cure for cancer or the cure for HIV infection.
Within ELPIs Foundation we have scientific advisors from a wide range of disciplines, including biomedicine, transhumanism, social sciences, neurosciences, complex systems, and systems biology. Our affiliate researchers are scientists who conduct research in their own facilities and share information and ideas with each other. We are always looking for visionary, ‘out-of the box’ scientific thinkers, those who ‘zoom out’ of reductionist views, and see aging in a wider perspective without being uncritically blinkered by existing dogma.
We ask questions such as: If aging happens because nature withholds resources from the soma and diverts these to the germ-line, how can we reverse this process and divert resources back to the soma in order to maximise biological repair? What is the role of digital hyperconnectivity of billions of humans (the Global Brain) in facilitating such a transition? Where does aging and the elimination of aging fit within an ever-evolving technological tendency of nature? Some ideas we currently explore are: * Induced Whole-Body Somatic Cell Turnover, for regenerative repair * Aging and evolutionary changes as applied to human sexual patterns, reproduction, ecosystems, society and the planet * The role of energy, entropy and thermodynamics in metasystem transitions with regards to human longevity *Theoretical aspects of Germ-line penetration
May symposium
In May 2014 we will be organising the second symposium on ‘Pathways to Indefinite Lifespans’ in Larnaca, Cyprus. This is a small, very select, highly focused meeting exploring the most cutting-edge research and ideas with regards to the total abolition of aging. We aim to discuss new insights and hypotheses in the fields of biomedical technology, evolutionary anthropology, complex systems, a hyperconnected society, and digital communications technology. The meeting will be accessible live online and will include both local and remote presentations. Those interested in coming need to contact me at: [email protected]. We are also exploring the possibility of offering PhD positions to exceptional candidates, in order to facilitate research in this area.
Men who are unemployed for more than two years show signs of faster ageing in their DNA, according to a study published today in the journal PLOS ONE.
Researchers at the University of Oulu, Finland and Imperial College, London arrived at this conclusion by studying blood samples collected from 5,620 men and women born in Northern Finland in 1966. The researchers measured the lengths of telomeres in their white blood cells, and compared them with the participants’ employment history for the prior three years, and found that extended unemployment (more than 500 days in three years) was associated with shorter telomere length.
Telomeres are repetitive DNA sequences at the ends of chromosomes, which protect the chromosomes from degrading. With every cell division, it appears that these telomeres get shorter. And the result of each shortening is that these cells degrade and age.
When cells are grown in a lab, their telomeres do indeed shorten each time the cells divide. This process can be used to find a cell’s “expiry date”, a prediction of when that cell will run out of telomeres and stop dividing. However, this does not seem to relate to the actual health of the cells.
In the new study, the researchers found that that on average, men who had been unemployed for more than two of the preceding three years were more than twice as likely to have short telomeres compared to men who were continuously employed. In women, there was no association between unemployment status and telomere length.
The researchers accounted for telomere length differences resulting from medical conditions, obesity, socio-economic status and early childhood environment.
Previous studies, noted by the study authors, have found a correlation between shorter telomeres and higher rates of age-related diseases like Type 2 diabetes and heart disease. The authors conclude that the reduction in these men’s telomeres may have been the result from the stress of long-term unemployment, adding to evidence of a direct connection between prolonged unemployment and poor health.
An abstract concept
Employment is something very abstract; an employed and unemployed body are apparently more or less the same. So it might seem surprising that such an abstract thing as employment can affect a body on the cellular level. But the same is true for how stimuli affect our brains: remote objects trigger electrochemical cascades in our visual system – and when we learn new things, gene expression in the brain changes. We are interactive creatures, with innumerable stimuli that are constantly shaping multiple processes in our bodies. In this sense, the hypothesis that employment experience has cellular effects is not surprising.
This was an association study, which means than under certain set of circumstances two variables are statistically linked. This study is therefore incapable of genuinely predicting whether unemployment is the cause, and short telomeres the effect. Perhaps the opposite is true: maybe people whose cells lose their telomeres also lose their jobs. More likely, an outside factor that shortens telomeres could have a limiting effect on success in the labour market. For example, such a factor might somehow contribute towards illness or pessimism.
Additionally, because the study was conducted in an isolated and genetically quite homogeneous population, the results of the study may be due to their genetic make-up as well as (or instead of) environmental effects.
In the end, we do not need a genetic study to know long-term unemployment is bad for people socially, medically and psychologically; there is plenty of evidence for that. Additionally, the bio-gerontology community (those who study the biological processes of ageing) recognises telomere attrition as one of the nine causes of the disease of ageing, including Type 2 diabetes and cardiovascular diseases.
Where this study does make a significant contribution is in recognising long-term, low-level stress as a major problem. In momentarily stressful situations, the instant fight-or-flight response stimulates us; but being under pressure for a long time with no relief wears us down. Prolonged stress is bad for memory and health, and could quite conceivably shorten telomeres – making an unemployed person significantly more unhealthy, with the effects persisting even after they get a job.
In the long run, what we really need to learn to slow or stop the ageing process is how to reduce or repair the damage done by stress.
The authors do not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article. They also have no relevant affiliations.
Grindhouse Wetware is a collective of makers and engineers founded on a basic principle – human augmentation should be accessible and open. All of our devices are built off of open source platforms. This allows our users to peer into the hardware and code of their implanted device and truly control their augmented experience. Grindhouse Wetware’s devices are tailored to Makers and DIY Transhumanists that want to build a specific, unique augmentation. What do you want to be?
After three years of development, our flagship project – Circadia, is in its final stages. Grindhouse Wetware is seeking financial support from individuals or organizations to facilitate the production of this device.
The Circadia implant records bio-medical data and transmits it to the user’s phone via bluetooth. Instead of a snapshot of the user’s state of health, the Circadia records the up-to-date status of the their well being. Grindhouse Wetware firmly believes that once an implant has been installed in an individual, it becomes a part of their person. As such, the data generated by the Circadia belongs to the user.
If you are interested in supporting Grindhouse Wetware and the Circadia implant, please contact me at [email protected] or 631−715−9209
Containing more than 160 essays from over 40 contributors, this edited volume of essays on the science, philosophy and politics of longevity considers the project of ending aging and abolishing involuntary death-by-disease from a variety of viewpoints: scientific, technological, philosophical, pragmatic, artistic. In it you will find not only information on the ways in which science and medicine are bringing about the potential to reverse aging and defeat death within many of our own lifetimes, as well as the ways that you can increase your own longevity today in order to be there for tomorrow’s promise, but also a glimpse at the art, philosophy and politics of longevity as well – areas that will become increasingly important as we realize that advocacy, lobbying and activism can play as large a part in the hastening of progress in indefinite lifespans as science and technology can.
The collection is edited by Franco Cortese. Its contributing authors include William H. Andrews, Ph.D., Rachel Armstrong, Ph.D., Jonathan Betchtel, Yaniv Chen, Clyde DeSouza, Freija van Diujne, Ph.D., John Ellis, Ph.D., Linda Gamble, Roen Horn, the International Longevity Alliance (ILA), Zoltan Istvan, David Kekich (President & C.E.O of Maximum Life Foundation), Randal A. Koene, Ph.D., Maria Konovalenko, M.Sc. (Program Coordinator for the Science for Life Extension Foundation), Marios Kyriazis, MD, M.Sc MIBiol, CBiol (Founder of the ELPIs Foundation for Indefinite Lifespans and the medical advisor for the British Longevity Society), John R. Leonard (Director of Japan Longevity Alliance), Alex Lightman, Movement for Indefinite Life Extension (MILE), Josh Mitteldorf, Ph.D., Tom Mooney (Executive Director of the Coalition to Extend Life), Max More, Ph.D. , B.J. Murphy, Joern Pallensen, Dick Pelletier, Hank Pellissier (Founder of Brighter Brains Institute), Giulio Prisco, Marc Ransford, Jameson Rohrer, Martine Rothblatt, Ph.D., MBA, JD., Peter Rothman (editor-in-chief of H+ Magazine), Giovanni Santostasi, Ph.D (Director of Immortal Life Magazine, Eric Schulke, Jason Silva , R.U. Sirius, Ilia Stambler, Ph.D (activist at the International Longevity Alliance), G. Stolyarov II (editor-in-chief of The Rational Argumentator), Winslow Strong, Jason Sussberg, Violetta Karkucinska, David Westmorland, Peter Wicks, Ph.D, and Jason Xu (director of Longevity Party China and Longevity Party Taiwan).
In his essay “Fifty Years Hence”, Winston Churchill speculated, “We shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under a suitable medium.”
At an event in London today, the first hamburger made entirely from meat grown through cell culture will be cooked and consumed before a live audience. In June at the TED Global conference in Edinburgh, Andras Forgacs took a step even beyond Churchill’s hopes. He unveiled the world’s first leather made from cells grown in the lab.
These are historic events. Ones that will change the discussion about lab-grown meat from blue-skies science to a potential consumer product which may soon be found on supermarket shelves and retail stores. And while some may perceive this development as a drastic shake-up in the world of agriculture, it really is part of the trajectory that agricultural technology is already following.
Creating abundance
While modern humans have been around for 160,000 years or so, agriculture only developed about 10,000 years ago, probably helping the human population to grow. A stable food source had tremendous impact on the development of our species and culture, as the time and effort once put towards foraging could now be put towards intellectual achievement and the development of our civilisation.
In recent history though, agricultural technology has developed with the goal of securing food supply. We have been using greenhouses to control the environment where crops grow. We use pesticides, fertilisers and genetic techniques to control and optimise output. We have created efficiencies in plant cultivation to produce more plants that yield more food than ever before.
These patterns in horticulture can be seen in animal husbandry too. From hunting to raising animals for slaughter and from factory farming to the use of antibiotics, hormones and genetic techniques, meat production today is so efficient that we grow more bigger animals faster than ever before. In 2012, the global herd has reached 60 billion land animals to feed 7 billion people.
The trouble with meat
Now, civilisation has come to a point where we are recognising that there are serious problems with the way we produce food. This mass produced food contributes towards our disease burden, challenges food safety, ravages the environment, and plays a major role in deforestation and loss of biodiversity. For meat production, in particular, manipulating animals has led to an epidemic of viruses, resistant bacteria and food-borne illness, apart from animal welfare issues.
But we may be seeing change brought by consumer demand. The public has started caring about the ethical, environmental and health impacts of food production. And beyond consumer demand for thoughtful products, ecological limits are forcing us to evaluate the way food is produced.
A damning report by the United Nations shows that today livestock raised for meat uses more than 80% of Earth’s agricultural land and 27% of Earth’s potable water supply. It produces 18% of global greenhouse gas emissions and the massive quantities of manure produced heavily pollute water. Deforestation and degradation of wildlife habitats happens largely in part to create feed crops, and factory farming conditions are breeding grounds for dangerous disease.
Making everyone on the planet take up vegetarianism is not an option. While there is much merit to reducing (and rejecting) meat consumption, sustainable dietary changes in the Western world will be more than compensated for by the meat intake of the growing middle class in developing countries like China and India.
The future is cultured
The logical step in the evolution of humanity’s food production capacity is to make meat from cells, rather than animals. After all, the meat we consume is simply a collection of tissues. So why should we grow the whole animals when we can only grow the part that we eat?
By doing this we avoid slaughter, animal welfare issues, disease development. This method, if commercialised, is also more sustainable. Animals do not have to be raised from birth, and no resources are shunted towards non-meat tissues. Compared to conventionally grown meat, cultured meat would require up to 99% less land, 96% less water, 45% less energy, and produce up to 96% less greenhouse gas emissions.
Also even without modern scientific tools, for hundreds of years we have been using bacterial cells, yeast and fungus for food purposes. With recent advances in tissue engineering, culturing mammalian cells for meat production seems like a sensible advancement.
Efficiency has been the primary driver of agricultural developments in the past. Now, it should be health, environment and ethics. We need for cultured meat to go beyond the proof of concept. We need it to be on supermarket shelves soon.
Avi Roy does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.
Immortal Life has complied an edited volume of essays, arguments, and debates about Immortalism titled Human Destiny is to Eliminate Death from many esteemed ImmortalLife.info Authors (a good number of whom are also Lifeboat Foundation Advisory Board members as well), such as Martine Rothblatt (Ph.D, MBA, J.D.), Marios Kyriazis (MD, MS.c, MI.Biol, C.Biol.), Maria Konovalenko (M.Sc.), Mike Perry (Ph.D), Dick Pelletier, Khannea Suntzu, David Kekich (Founder & CEO of MaxLife Foundation), Hank Pellissier (Founder of Immortal Life), Eric Schulke & Franco Cortese (the previous Managing Directors of Immortal Life), Gennady Stolyarov II, Jason Xu (Director of Longevity Party China and Longevity Party Taiwan), Teresa Belcher, Joern Pallensen and more. The anthology was edited by Immortal Life Founder & Senior Editor, Hank Pellissier.
This one-of-a-kind collection features ten debates that originated at ImmortalLife.info, plus 36 articles, essays and diatribes by many of IL’s contributors, on topics from nutrition to mind-filing, from teleomeres to “Deathism”, from libertarian life-extending suggestions to religion’s role in RLE to immortalism as a human rights issue.
The book is illustrated with famous paintings on the subject of aging and death, by artists such as Goya, Picasso, Cezanne, Dali, and numerous others.
The book was designed by Wendy Stolyarov; edited by Hank Pellissier; published by the Center for Transhumanity. This edited volume is the first in a series of quarterly anthologies planned by Immortal Life
This Immortal Life Anthology includes essays, articles, rants and debates by and between some of the leading voices in Immortalism, Radical Life-Extension, Superlongevity and Anti-Aging Medicine.
A (Partial) List of the Debaters & Essay Contributors:
Martine Rothblatt Ph.D, MBA, J.D. — inventor of satellite radio, founder of Sirius XM and founder of the Terasem Movement, which promotes technological immortality. Dr. Rothblatt is the author of books on gender freedom (Apartheid of Sex, 1995), genomics (Unzipped Genes, 1997) and xenotransplantation (Your Life or Mine, 2003).
Marios Kyriazis MD, MSc, MIBiol, CBiol. founded the British Longevity Society, was the first to address the free-radical theory of aging in a formal mainstream UK medical journal, has authored dozens of books on life-extension and has discussed indefinite longevity in 700 articles, lectures and media appearances globally.
Maria Konovalenko is a molecular biophysicist and the program coordinator for the Science for Life Extension Foundation. She earned her M.Sc. degree in Molecular Biological Physics at the Moscow Institute of Physics and Technology. She is a co-founder of the International Longevity Alliance.
Jason Xu is the director of Longevity Party China and Longevity Party Taiwan, and he was an intern at SENS.
Mike Perry, PhD. has worked for Alcor since 1989 as Care Services Manager. He has authored or contributed to the automated cooldown and perfusion modeling programs. He is a regular contributor to Alcor newsletters. He has been a member of Alcor since 1984.
David A. Kekich, Founder, President & C.E.O Maximum Life Extension Foundation, works to raise funds for life-extension research. He serves as a Board Member of the American Aging Association, Life Extension Buyers’ Club and Alcor Life Extension Foundation Patient Care Trust Fund. He authored Smart, Strong and Sexy at 100?, a how-to book for extreme life extension.
Eric Schulke is the founder of the Movement for Indefinite Life Extension (MILE). He was a Director, Teams Coordinator and ran Marketing & Outreach at the Immortality Institute, now known as Longecity, for 4 years. He is the Co-Managing Director of Immortal Life.
Hank Pellissier is the Founder & Senior Editor of ImmortaLife.info. Previously, he was the founder/director of Transhumanity.net. Before that, he was Managing Director of the Institute for Ethics and Emerging Technology (ieet.org). He’s written over 120 futurist articles for IEET, Hplusmagazine.com, Transhumanity.net, ImmortalLife.info and the World Future Society.
Franco Cortese is on the Advisory Board for Lifeboat Foundation on their Scientific Advisory Board (Life-Extension Sub-Board) and their Futurism Board. He is the Co-Managing Director alongside of Immortal Life and a Staff Editor for Transhumanity. He has written over 40 futurist articles and essays for H+ Magazine, The Institute for Ethics & Emerging Technologies, Immortal Life, Transhumanity and The Rational Argumentator.
Gennady Stolyarov II is a Staff Editor for Transhumanity, Contributor to Enter Stage Right, Le Quebecois Libre, Rebirth of Reason, Ludwig von Mises Institute, Senior Writer for The Liberal Institute, and Editor-in-Chief of The Rational Argumentator.
Brandon King is Co-Director of the United States Longevity Party.
Khannea Suntzu is a transhumanist and virtual activist, and has been covered in articles in Le Monde, CGW and Forbes.
Teresa Belcher is an author, blogger, Buddhist, consultant for anti-aging, life extension, healthy life style and happiness, and owner of Anti-Aging Insights.
Dick Pelletier is a weekly columnist who writes about future science and technologies for numerous publications.
Joern Pallensen has written articles for Transhumanity and the Institute for Ethics and Emerging Technologies.
CONTENTS:
Editor’s Introduction
DEBATES
1. In The Future, With Immortality, Will There Still Be Children?
2. Will Religions promising “Heaven” just Vanish, when Immortality on Earth is attained?
3. In the Future when Humans are Immortal — what will happen to Marriage?
4. Will Immortality Change Prison Sentences? Will Execution and Life-Behind-Bars be… Too Sadistic?
5. Will Government Funding End Death, or will it be Attained by Private Investment?
6. Will “Meatbag” Bodies ever be Immortal? Is “Cyborgization” the only Logical Path?
7. When Immortality is Attained, will People be More — or Less — Interested in Sex?
8. Should Foes of Immortality be Ridiculed as “Deathists” and “Suicidalists”?
9. What’s the Best Strategy to Achieve Indefinite Life Extension?
ESSAYS
1. Maria Konovalenko:
I am an “Aging Fighter” Because Life is the Main Human Right, Demand, and Desire
2. Mike Perry:
Deconstructing Deathism — Answering Objections to Immortality
3. David A. Kekich:
How Old Are You Now?
4. David A. Kekich:
Live Long… and the World Prospers
5. David A. Kekich:
107,000,000,000 — what does this number signify?
6. Franco Cortese:
Religion vs. Radical Longevity: Belief in Heaven is the Biggest Barrier to Eternal Life?!
7. Dick Pelletier:
Stem Cells and Bioprinters Take Aim at Heart Disease, Cancer, Aging
8. Dick Pelletier:
Nanotech to Eliminate Disease, Old Age; Even Poverty
9. Dick Pelletier:
Indefinite Lifespan Possible in 20 Years, Expert Predicts
10. Dick Pelletier:
End of Aging: Life in a World where People no longer Grow Old and Die
11. Eric Schulke:
We Owe Pursuit of Indefinite Life Extension to Our Ancestors
12. Eric Schulke:
Radical Life Extension and the Spirit at the core of a Human Rights Movement
13. Eric Schulke:
MILE: Guide to the Movement for Indefinite Life Extension
14. Gennady Stolyarov II:
The Real War and Why Inter-Human Wars Are a Distraction
15. Gennady Stolyarov II:
The Breakthrough Prize in Life Sciences — turning the tide for life extension
16. Gennady Stolyarov II:
Six Libertarian Reforms to Accelerate Life Extension
17. Hank Pellissier:
Wake Up, Deathists! — You DO Want to LIVE for 10,000 Years!
18. Hank Pellissier:
Top 12 Towns for a Healthy Long Life
19. Hank Pellissier:
This list of 30 Billionaires — Which One Will End Aging and Death?
20. Hank Pellissier:
People Who Don’t Want to Live Forever are Just “Suicidal”
It may be possible one day to use effective biotechnological therapies in order to achieve extreme lifespans. In the meantime, instead of just waiting for these therapies, it may be more fruitful to live a life of constant stimulation, hyper-connection and avoidance of regularity. This is something that everybody can do today, and may have a direct impact upon radical life extension, not only for the individual but also for society.
For some time now I have been advocating the notion that exposure to meaningful information may be one way of achieving radical life extension. By meaningful information I mean anything that requires action, and not just feeding your brain with routine sets of data. Examples of this include being hyper-connected in a digital world, an enriched environment (both in the personal space and in society as a whole), a hormetic lifestyle, behavioural models such as a goal-seeking behaviour, search for excellence, and a bias for action, as well as the pursuit innovation, diversification, creativity and novelty. Most importantly, the avoidance of routine and mediocrity.
This information-rich lifestyle up-regulates the function of the brain and may have an impact upon cell immortalisation. In my latest paper (http://arxiv.org/abs/1306.2734 I provide an explanation of the exact mechanisms. I argue that the relentless exposure to useful information creates new and persisting demands for energy resources in order for this information to be assimilated by the neurons. If this process continues for some time, there will come a point where our biological mechanisms will undergo a phase transition, in effect creating a new biology. Not one based on sex and reproduction but one based on information and somatic survival.
One possible mechanism involves the immortalisation sequences of germ cells. As we know, the DNA in germ cells is essentially immortal because it is somehow able to repair age-related damage effectively. Recent research shows that some of these immortalisation mechanisms do not originate from the germ cells but from the somatic cells! In other words, our bodily cells create biological material such as error-free sequences of DNA and instead of using this themselves for their own survival, they pass it on to the germ cells to assure the survival of the species. This means that the germ-line remains immortal whereas the bodily cells eventually age and die.
The process may be forcibly changed, by overloading the system with high quality actionable information. As explained above, the assimilation of this information demands so much energy and resources from the organism that there will come a point when nature will have to make a choice: is it more economical from the thermodynamic point of view to continue the current cycle of birth, aging and death (with an immortal DNA), or is it better to downgrade this model and favour a new process of somatic survival and improved development in the same individual who would be able to live much longer? The force of evolution in a modern technological, information-laden niche may eventually favour the latter.
In this essay I argue that technologies and techniques used and developed in the fields of Synthetic Ion Channels and Ion Channel Reconstitution, which have emerged from the fields of supramolecular chemistry and bio-organic chemistry throughout the past 4 decades, can be applied towards the purpose of gradual cellular (and particularly neuronal) replacement to create a new interdisciplinary field that applies such techniques and technologies towards the goal of the indefinite functional restoration of cellular mechanisms and systems, as opposed to their current proposed use of aiding in the elucidation of cellular mechanisms and their underlying principles, and as biosensors.
In earlier essays (see here and here) I identified approaches to the synthesis of non-biological functional equivalents of neuronal components (i.e. ion-channels ion-pumps and membrane sections) and their sectional integration with the existing biological neuron — a sort of “physical” emulation if you will. It has only recently come to my attention that there is an existing field emerging from supramolecular and bio-organic chemistry centered around the design, synthesis, and incorporation/integration of both synthetic/artificial ion channels and artificial bilipid membranes (i.e. lipid bilayer). The potential uses for such channels commonly listed in the literature have nothing to do with life-extension however, and the field is to my knowledge yet to envision the use of replacing our existing neuronal components as they degrade (or before they are able to), rather seeing such uses as aiding in the elucidation of cellular operations and mechanisms and as biosensors. I argue here that the very technologies and techniques that constitute the field (Synthetic Ion-Channels & Ion-Channel/Membrane Reconstitution) can be used towards the purpose of the indefinite-longevity and life-extension through the iterative replacement of cellular constituents (particularly the components comprising our neurons – ion-channels, ion-pumps, sections of bi-lipid membrane, etc.) so as to negate the molecular degradation they would have otherwise eventually undergone.
While I envisioned an electro-mechanical-systems approach in my earlier essays, the field of Synthetic Ion-Channels from the start in the early 70’s applied a molecular approach to the problem of designing molecular systems that produce certain functions according to their chemical composition or structure. Note that this approach corresponds to (or can be categorized under) the passive-physicalist sub-approach of the physicalist-functionalist approach (the broad approach overlying all varieties of physically-embodied, “prosthetic” neuronal functional replication) identified in an earlier essay.
The field of synthetic ion channels is also referred to as ion-channel reconstitution, which designates “the solubilization of the membrane, the isolation of the channel protein from the other membrane constituents and the reintroduction of that protein into some form of artificial membrane system that facilitates the measurement of channel function,” and more broadly denotes “the [general] study of ion channel function and can be used to describe the incorporation of intact membrane vesicles, including the protein of interest, into artificial membrane systems that allow the properties of the channel to be investigated” [1]. The field has been active since the 1970s, with experimental successes in the incorporation of functioning synthetic ion channels into biological bilipid membranes and artificial membranes dissimilar in molecular composition and structure to biological analogues underlying supramolecular interactions, ion selectivity and permeability throughout the 1980’s, 1990’s and 2000’s. The relevant literature suggests that their proposed use has thus far been limited to the elucidation of ion-channel function and operation, the investigation of their functional and biophysical properties, and in lesser degree for the purpose of “in-vitro sensing devices to detect the presence of physiologically-active substances including antiseptics, antibiotics, neurotransmitters, and others” through the “… transduction of bioelectrical and biochemical events into measurable electrical signals” [2].
Thus my proposal of gradually integrating artificial ion-channels and/or artificial membrane sections for the purpse of indefinite longevity (that is, their use in replacing existing biological neurons towards the aim of gradual substrate replacement, or indeed even in the alternative use of constructing artificial neurons to, rather than replace existing biological neurons, become integrated with existing biological neural networks towards the aim of intelligence amplification and augmentation while assuming functional and experiential continuity with our existing biological nervous system) appears to be novel, while the notion of artificial ion-channels and neuronal membrane systems ion general had already been conceived (and successfully created/experimentally-verified, though presumably not integrated in-vivo).
The field of Functionally-Restorative Medicine (and the orphan sub-field of whole-brain-gradual-substrate-replacement, or “physically-embodied” brain-emulation if you like) can take advantage of the decades of experimental progress in this field, incorporating both the technological and methodological infrastructures used in and underlying the field of Ion-Channel Reconstitution and Synthetic/Artificial Ion Channels & Membrane-Systems (and the technologies and methodologies underlying their corresponding experimental-verification and incorporation techniques) for the purpose of indefinite functional restoration via the gradual and iterative replacement of neuronal components (including sections of bilipid membrane, ion channels and ion pumps) by MEMS (micro-electrocal-mechanical-systems) or more likely NEMS (nano-electro-mechanical systems).
The technological and methodological infrastructure underlying this field can be utilized for both the creation of artificial neurons and for the artificial synthesis of normative biological neurons. Much work in the field required artificially synthesizing cellular components (e.g. bilipid membranes) with structural and functional properties as similar to normative biological cells as possible, so that the alternative designs (i.e. dissimilar to the normal structural and functional modalities of biological cells or cellular components) and how they affect and elucidate cellular properties, could be effectively tested. The iterative replacement of either single neurons, or the sectional replacement of neurons with synthesized cellular components (including sections of the bi-lipid membrane, voltage-dependent ion-channels, ligand-dependent ion channels, ion pumps, etc.) is made possible by the large body of work already done in the field. Consequently the technological, methodological and experimental infrastructures developed for the fields of Synthetic
Ion-Channels and Ion-Channel/Artificial-Membrane-Reconstitution can be utilized for the purpose of a.) iterative replacement and cellular upkeep via biological analogues (or not differing significantly in structure or functional & operational modality to their normal biological counterparts) and/or b.) iterative replacement with non-biological analogues of alternate structural and/or functional modalities.
Rather than sensing when a given component degrades and then replacing it with an artificially-synthesized biological or non-biological analogue, it appears to be much more efficient to determine the projected time it takes for a given component to degrade or otherwise lose functionality, and simply automate the iterative replacement in this fashion, without providing in-vivo systems for detecting molecular or structural degradation. This would allow us to achieve both experimental and pragmatic success in such cellular-prosthesis sooner, because it doesn’t rely on the complex technological and methodological infrastructure underlying in-vivo sensing, especially on the scale of single neuron components like ion-channels, and without causing operational or functional distortion to the components being sensed.
A survey of progress in the field [3] lists several broad design motifs. I will first list the deign motifs falling within the scope of the survey, and the examples it provides. Selections from both papers are meant to show the depth and breadth of the field, rather than to elucidate the specific chemical or kinetic operations under the purview of each design-variety.
For a much more comprehensive, interactive bibliography of papers falling within the field of Synthetic Ion-Channels or constituting the historical foundations of the field, see Jon Chui’s online biography here, which charts the developments in this field up until 2011.
First Survey
Unimolecular ion channels:
Examples include a.) synthetic ion channels with oligocrown ionophores, [5] b.) using a-helical peptide scaffolds and rigid push–pull p-octiphenyl scaffolds for the recognition of polarized membranes, [6] and c.) modified varieties of the b-helical scaffold of gramicidin A [7]
Barrel-stave supramolecules:
Examples of this general class falling include avoltage-gated synthetic ion channels formed by macrocyclic bolaamphiphiles and rigidrod p-octiphenyl polyols [8].
Macrocyclic, branched and linear non-peptide bolaamphiphiles as staves:
Examples of this sub-class include synthetic ion channels formed by a.) macrocyclic, branched and linear bolaamphiphiles and dimeric steroids, [9] and by b.) non-peptide macrocycles, acyclic analogs and peptide macrocycles [respectively] containing abiotic amino acids [10].
Dimeric steroid staves:
Examples of this sub-class include channels using polydroxylated norcholentriol dimer [11].
pOligophenyls as staves in rigid rod b barrels:
Examples of this sub-class include “cylindrical self-assembly of rigid-rod b-barrel pores preorganized by the nonplanarity of p-octiphenyl staves in octapeptide-p-octiphenyl monomers” [12].
Synthetic Polymers:
Examples of this sub-class include synthetic ion channels and pores comprised of a.) polyalanine, b.) polyisocyanates, c.) polyacrylates, [13] formed by i.) ionophoric, ii.) ‘smart’ and iii.) cationic polymers [14]; d.) surface-attached poly(vinyl-n-alkylpyridinium) [15]; e.) cationic oligo-polymers [16] and f.) poly(m-phenylene ethylenes) [17].
Helical b-peptides (used as staves in barrel-stave method):
Examples of this class include: a.) cationic b-peptides with antibiotic activity, presumably acting as amphiphilic helices that form micellar pores in anionic bilayer membranes [18].
Monomeric steroids:
Examples of this sub-class falling include synthetic carriers, channels and pores formed by monomeric steroids [19], synthetic cationic steroid antibiotics [that] may act by forming micellar pores in anionic membranes [20], neutral steroids as anion carriers [21] and supramolecular ion channels [22].
Complex minimalist systems:
Examples of this sub-class falling within the scope of this survey include ‘minimalist’ amphiphiles as synthetic ion channels and pores [23], membrane-active ‘smart’ double-chain amphiphiles, expected to form ‘micellar pores’ or self-assemble into ion channels in response to acid or light [24], and double-chain amphiphiles that may form ‘micellar pores’ at the boundary between photopolymerized and host bilayer domains and representative peptide conjugates that may self assemble into supramolecular pores or exhibit antibiotic activity [25].
Non-peptide macrocycles as hoops:
Examples of this sub-class falling within the scope of this survey include synthetic ion channels formed by non-peptide macrocycles acyclic analogs [26] and peptide macrocycles containing abiotic amino acids [27].
Peptide macrocycles as hoops and staves:
Examples of this sub-class include a.) synthetic ion channels formed by self-assembly of macrocyclic peptides into genuine barrel-hoop motifs that mimic the b-helix of gramicidin A with cyclic b-sheets. The macrocycles are designed to bind on top of channels and cationic antibiotics (and several analogs) are proposed to form micellar pores in anionic membranes [28]; b.) synthetic carriers, antibiotics (and analogs) and pores (and analogs) formed by macrocyclic peptides with non-natural subunits. [Certain] macrocycles may act as b-sheets, possibly as staves of b-barrel-like pores [29]; c.) bioengineered pores as sensors. Covalent capturing and fragmentations [have been] observed on the single-molecule level within engineered a-hemolysin pore containing an internal reactive thiol [30].
Summary
Thus even without knowledge of supramolecular or organic chemistry, one can see that a variety of alternate approaches to the creation of synthetic ion channels, and several sub-approaches within each larger ‘design motif’ or broad-approach, not only exist but have been experimentally verified, varietized and refined.
Second Survey
The following selections [31] illustrate the chemical, structural and functional varieties of synthetic ions categorized according to whether they are cation-conducting or anion-conducting, respectively. These examples are used to further emphasize the extent of the field, and the number of alternative approaches to synthetic ion-channel design, implementation, integration and experimental-verification already existent. Permission to use all the following selections and figures were obtained from the author of the source.
There are 6 classical design-motifs for synthetic ion-channels, categorized by structure, that are identified within the paper:
“The first non-peptidic artificial ion channel was reported by Kobuke et al. in 1992” [33].
“The channel contained “an amphiphilic ion pair consisting of oligoether-carboxylates and mono- (or di-) octadecylammoniumcations. The carboxylates formed the channel core and the cations formed the hydrophobic outer wall, which was embedded in the bilipid membrane with a channel length of about 24 to 30 Å. The resultant ion channel, formed from molecular self-assembly, is cation selective and voltage-dependent” [34].
“Later, Kokube et al. synthesized another channel comprising of resorcinol based cyclic tetramer as the building block. The resorcin-[4]-arenemonomer consisted of four long alkyl chains which aggregated to forma dimeric supramolecular structure resembling that of Gramicidin A” [35]. “Gokel et al. had studied [a set of] simple yet fully functional ion channels known as “hydraphiles” [39].
“An example (channel 3) is shown in Figure 1.6, consisting of diaza-18-crown-6 crown ether groups and alkyl chain as side arms and spacers. Channel 3 is capable of transporting protons across the bilayer membrane” [40].
“A covalently bonded macrotetracycle4 (Figure 1.8) had shown to be about three times more active than Gokel’s ‘hydraphile’ channel, and its amide-containing analogue also showed enhanced activity” [44].
“Inorganic derivative using crown ethers have also been synthesized. Hall et. al synthesized an ion channel consisting of a ferrocene and 4 diaza-18-crown-6 linked by 2 dodecyl chains (Figure 1.9). The ion channel was redox-active as oxidation of the ferrocene caused the compound to switch to an inactive form” [45]
B STAVES:
“These are more difficult to synthesize [in comparison to unimolecular varieties] because the channel formation usually involves self-assembly via non-covalent interactions” [47].“A cyclic peptide composed of even number of alternating D- and L-amino acids (Figure 1.10) was suggested to form barrel-hoop structure through backbone-backbone hydrogen bonds by De Santis” [49].
“A tubular nanotube synthesized by Ghadiri et al. consisting of cyclic D and L peptide subunits form a flat, ring-shaped conformation that stack through an extensive anti-parallel β-sheet-like hydrogen bonding interaction (Figure 1.11)” [51].
“Experimental results have shown that the channel can transport sodium and potassium ions. The channel can also be constructed by the use of direct covalent bonding between the sheets so as to increase the thermodynamic and kinetic stability” [52].
“By attaching peptides to the octiphenyl scaffold, a β-barrel can be formed via self-assembly through the formation of β-sheet structures between the peptide chains (Figure 1.13)” [53].
“The same scaffold was used by Matile etal. to mimic the structure of macrolide antibiotic amphotericin B. The channel synthesized was shown to transport cations across the membrane” [54].
“Attaching the electron-poor naphthalenediimide (NDIs) to the same octiphenyl scaffold led to the hoop-stave mismatch during self-assembly that results in a twisted and closed channel conformation (Figure 1.14). Adding the compleentary dialkoxynaphthalene (DAN) donor led to the cooperative interactions between NDI and DAN that favors the formation of barrel-stave ion channel.” [57].
MICELLAR
“These aggregate channels are formed by amphotericin involving both sterols and antibiotics arranged in two half-channel sections within the membrane” [58].
“An active form of the compound is the bolaamphiphiles (two-headed amphiphiles). (Figure 1.15) shows an example that forms an active channel structure through dimerization or trimerization within the bilayer membrane. Electrochemical studies had shown that the monomer is inactive and the active form involves dimer or larger aggregates” [60].
ANION CONDUCTING CHANNELS:
“A highly active, anion selective, monomeric cyclodextrin-based ion channel was designed by Madhavan et al (Figure 1.16). Oligoether chains were attached to the primary face of the β-cyclodextrin head group via amide bonds. The hydrophobic oligoether chains were chosen because they are long enough to span the entire lipid bilayer. The channel was able to select “anions over cations” and “discriminate among halide anions in the order I-> Br-> Cl- (following Hofmeister series)” [61].
“The anion selectivity occurred via the ring of ammonium cations being positioned just beside the cyclodextrin head group, which helped to facilitate anion selectivity. Iodide ions were transported the fastest because the activation barrier to enter the hydrophobic channel core is lower for I- compared to either Br- or Cl-“ [62]. “A more specific artificial anion selective ion channel was the chloride selective ion channel synthesized by Gokel. The building block involved a heptapeptide with Proline incorporated (Figure 1.17)” [63].
Cellular Prosthesis: Inklings of a New Interdisciplinary Approach
The paper cites “nanoreactors for catalysis and chemical or biological sensors” and “interdisciplinary uses as nano –filtration membrane, drug or gene delivery vehicles/transporters as well as channel-based antibiotics that may kill bacterial cells preferentially over mammalian cells” as some of the main applications of synthetic ion-channels [65], other than their normative use in elucidating cellular function and operation.
However, I argue that a whole interdisciplinary field and heretofore-unrecognized new approach or sub-field of Functionally-Restorative Medicine is possible through taking the technologies and techniques involved in in constructing, integrating, and experimentally-verifying either a.) non-biological analogues of ion-channels & ion-pumps (thus trans-membrane membrane proteins in general, also sometimes referred to as transport proteins or integral membrane proteins) and membranes (which include normative bilipid membranes, non-lipid membranes and chemically-augmented bilipid membranes), and b.) the artificial synthesis of biological analogues of ion-channels, ion-pumps and membranes, which are structurally and chemically equivalent to naturally-occurring biological components but which are synthesized artificially – and applying such technologies and techniques toward the purpose the gradual replacement of our existing biological neurons constituting our nervous systems – or at least those neuron-populations that comprise the neo- and prefrontal-cortex, and through iterative procedures of gradual replacement thereby achieving indefinite-longevity. There is still work to be done in determining the comparative advantages and disadvantages of various structural and functional (i.e. design) motifs, and in the logistics of implanting the iterative replacement or reconstitution of ion-channels, ion-pumps and sections of neuronal membrane in-vivo.
The conceptual schemes outlined in Concepts for Functional Replication of Biological Neurons [66], Gradual Neuron Replacement for the Preservation of Subjective-Continuity [67] and Wireless Synapses, Artificial Plasticity, and Neuromodulation [68] would constitute variations on the basic approach underlying this proposed, embryonic interdisciplinary field. Certain approaches within the fields of nanomedicine itself, particularly those approaches that constitute the functional emulation of existing cell-types, such as but not limited to Robert Freitas’s conceptual designs for the functional emulation of the red blood cell (a.k.a. erythrocytes, haematids) [69], i.e. the Resperocyte, itself should be seen as falling under the purview of this new approach, although not all approaches to Nanomedicine (diagnostics, drug-delivery and neuroelectronic interfacing) constitute the physical (i.e. electromechanical, kinetic and/or molecular physically-embodied) and functional emulation of biological cells.
The field of functionally-restorative medicine in general (and of nanomedicine in particular) and the field of supramolecular and organic chemistry converge here, where these technological, methodological, and experimental infrastructures developed in field of Synthetic Ion-Channels and Ion Channel Reconstitution can be employed to develop a new interdisciplinary approach that applies the logic of prosthesis to the cellular and cellular-component (i.e. sub-cellular) scale; same tools, new use. These techniques could be used to iteratively replace the components of our neurons as they degrade, or to replace them with more robust systems that are less susceptible to molecular degradation. Instead of repairing the cellular DNA, RNA and protein transcription and synthesis machinery, we bypass it completely by configuring and integrating the neuronal components (ion-channels, ion-pumps and sections of bilipid membrane) directly.
Thus I suggest that theoreticians of nanomedicine look to the large quantity of literature already developed in the emerging fields of synthetic ion-channels and membrane-reconstitution, towards the objective of adapting and applying existing technologies and methodologies to the new purpose of iterative maintenance, upkeep and/or replacement of cellular (and particularly neuronal) constituents with either non-biological analogues or artificially-synthesized-but-chemically/structurally-equivalent biological analogues.
This new sub-field of Synthetic Biology needs a name to differentiate it from the other approaches to Functionally-Restorative Medicine. I suggest the designation ‘cellular prosthesis’.
References:
[1] Williams (1994)., An introduction to the methods available for ion channel reconstitution. in D.C Ogden Microelectrode techniques, The Plymouth workshop edition, CambridgeCompany of Biologists.
[2] Tomich, J., Montal, M. (1996). U.S Patent No. 5,16,890. Washington, DC: U.S. Patent and Trademark Office.
[69] Freitas Jr., R., (1998). “Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell”. Artificial Cells, Blood Substitutes, and Immobil. Biotech. (26): 411–430. Access: http://www.ncbi.nlm.nih.gov/pubmed/9663339
