Pluslectic – The Dialectic of Positive Feedback – Article by Pedro Villanueva

Pluslectic – The Dialectic of Positive Feedback – Article by Pedro Villanueva

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Pedro Villanueva


Editor’s Note: In this guest article, Pedro Villanueva outlines a new concept of pluslectic philosophy, which endeavors to be a method of thinking and forward-looking feedback (feedforward) which would characterize future advanced civilizations of enhanced humans. The U.S. Transhumanist Party publishes this article to motivate thought regarding how philosophical systems would need to evolve in order to recognize, characterize, and provide ethical guidance in a world of enhanced, augmented “plus-humans” – i.e., transhumansm. It appears that article was originally written in Spanish. The author’s translation from Spanish to English was edited further in a way that sought to preserve and reflect the author’s intent while restructuring various sentences to reflect the English rules of grammar. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, January 14, 2018

What is the pluslectic? The term stems from the Latin “plus”, signifying “more”, “added”, and “positive”.

A philosophical method that differs from the classical dialectic of Hegel and Marx, pluslectic philosophy values the input of the positive facts of growth throughout the world.

First think what happens with society and history. Our world over time since the beginning of civilization has been almost dystopian, as said Slavoj Zizek, […] “The real thing is a grain of sand that prevents us from a functioning unimpeded; a shock traumatic that disrupts the balance of the symbolic universe of the subject.” [1]

With the development of capitalism, develops also nihilism; it refers to a “belief” or faith that all values are meaningless or useless and that nothing can be really known or communicated, since humans can never know the truth and should leave social deception.

Nihilists believe in these 3 things:

1. There is not reasonable proof of the existence of a “supreme ruler” or a “creator”.

2. The “moral truth” is unknown.

3. The universal ethics is impossible.

Nietzsche says the following: “What matter to me others? Others are only human. Be superior to humanity by the force, by the temple, for contempt… ” [2]

In the 20th century and early 21st century, there has deepened the social disorientation and the existence of a society without sense, with the philosophy of the postmodernism of Lyotard. Lipovetsky examines a “postmodern” society marked, according to him, by a separation of the public sphere, and at the same time a loss of the sense of the large collective institutions (social and political) and “open” culture based on the regulation of human relations. Grace, hedonism, customization of the processes of socialization, permissive education, sexual liberation, focus on mood all characterize such a society.

This vision of society poses a neoindividualism of a narcissistic type and, moreover, what Lipovetsky called “the second individualist revolution”. The Post-Structuralists, with the deconstruction approach of Derrida, and Paul Virilio, with his thought of the aesthetics of disappearance where speed rules in the political, economic and cultural realms of human existence, are examples of this phenomenon.

I’ll explain the evolution of the concept of modern dialectic in the main figures of the philosophers Fitche, Hegel and Marx.

For Johann Gottlieb Fichte, I, the subject, is derived from all and the logical principles logical of identity and denial, to assert oneself begets opposition – “not me” – and both are subordinated to a principle of total unity. As the self comes into contradiction with himself and opposition to the “not me”, it eliminates this opposition by limiting both flows in an endless process, which is formulated in the dialectic triad: thesis, antithesis, and synthesis. [3]

The German philosopher Georg Wilhelm Friedrich Hegel applies the term “dialectic” to his philosophical system and its logic focused on the future, contradiction, and change, which replaces the principles of identity and non-contradiction, by the incessant transformation of things and the unity of opposites. Hegel thought that the evolution of the Idea occurs through a dialectical process, i.e., a concept confronts its opposite and as a result of this conflict, rises a third synthesis. The synthesis is more loaded with truth than the previous two opposites. The work of Hegel is based on an idealistic conception of a universal mind that, through evolution, aims to reach the highest limit of self-consciousness and freedom. [4]

The German philosopher Karl Marx applied the concept of dialectic to the social and economic processes. The so-called dialectical materialism of Marx is often considered as a revision of the Hegelian system. This proposed a solution to a widespread problem of economic ends through three concepts: thesis, antithesis, and synthesis. The first was the source of the problem in this property of the  capital concentrated in the bourgeois class. The second, proletarian, class, the creator of the value with their work, was stripped of all means of production. These two, according to Marx, will give as a synthesis communism, the social ownership of the means of production. [5]

Let’s bring to the discussion general systems theory and its importance. The advance of technology exposes the complexity of general systems theory when compared to the modern dialectic.

The general systems theory was conceived by Ludwig von Bertalanffy in the 1940s, in order to form a practical model for conceptualizing the phenomena that the mechanistic reduction of the classical approach to science could not explain. In particular, general systems theory seems to provide a unifying theoretical framework for the natural sciences and the social sciences, needing in so doing to employ concepts such as “organization”, “whole”, “globalization”, and “dynamic interaction”; the linear is replaced by the circular. None of this was easily understandable by the analytical methods of the pure sciences. The individual lost importance in favor of the interdisciplinary approach. [6]

During the 1930s, Wiener worked with doctors and engineers and examined the parallels between human beings and electrical systems. As a result of such research, important concepts of feedback were developed, with the researchers studying more closely those systems that incorporated them.

These concepts of feedback, by which information was introduced to machines, led to the emergence of Cybernetics as the adaptation different from the mechanistic theory. The circularity and feedback processes are passed to the common elements of entire system, and Wiener called them “anti-entropic local phenomena”.

The behavior of a driver’s car on a road would be a clear example of negative feedback, since the driver would receive information from the limits of the road that could produce correcting deviations with the steering wheel. The thermostat would be another example of negative feedback, to which we referred above.

Any feedback would take into account the information on past actions, and with them would determine further actions to follow, creating a structure more complex than the linear or circular causality.

About Feedback

In this type of chain, each link is modified and changes its interaction, and this modification occurs in a circular process known as feedback loop (feedback loop).

We can find examples of the previously articulated concept. Thus, a spider that paralyzes a fly with its stinger is involved in a process of spending a fixed amount of power from “a” to “b”; a jellyfish stinging a human hand can participate in a feedback loop from “a” to “b” and “b” (hand stung) back to “a” (in the form of circle). In the first model the effect of “a” on “b” is not returned to the system (a + b); in the second, the message part of the affected “b” (production) and returned to the system (a + b) as feed-back (received power). The general systems theory holds that transactions are circular and create spirals of exchange that become progressively more complex.

Feedback can be positive or negative.

Positive feedback: Growth of differences – “snowball” – when left to operate, leads to the destruction of the system.

Negative feedback (e.g., a thermostat): Leads to an adaptive behavior or having a purpose, a purpose.

In both cases, there is an anointing of transfer by means of which the received energy is converted into the result, which, in turn, is reintroduced into the system as information about the result.

In the case of negative feedback, the system uses this information to activate its homeostatic mechanisms and to reduce the deviation of the production system and thus maintain a “steady state”.

In the case of positive feedback, the information is used to activate the mechanisms of growth (morphogenic mechanisms) that lead to a disruption of homeostasis and a movement toward change – i.e., the positive feedback serves to increase the deviation of the production.

Therefore, when a system uses negative feedback, the system is auto-corrects and returns to the initial state (i.e., does not change). When a system uses positive feedback, the system goes to another state (change).

Andréi Korotáyev (Андрей Витальевич Коротаев, born in 1961) is an anthropologist, economist, historian, and sociologist, with important contributions to the world system theory and mathematical models of social and economic macrodynamics.

Andrey Korotayev’s major contributions belong to four areas: mathematical models of the dynamics of social, economic, and historical phenomena (cliodynamics).

In the field of cliodynamics, Korotayev proposed one of the most convincing explanations for the doomsday argument of Heinz von Foerster.

In collaboration with his colleagues Artemi Malkov and Daria Khaltourina, Andrey Korotayev showed that, until the 1970s, the hyperbolic growth of the  world population was accompanied by a hyperbolic growth of the second degree of the world’s GDP, from which developed a series of mathematical models which both described this phenomenon as the theory of world system, the correlation between the hyperbolic growth of the world population and the hyperbolic of second degree of global GDP growth, observed until the early 1970s, corresponds to a  positive feedback. (Positive feedback is one of the mechanisms of  feedback by which outcomes or outputs of a system cause cumulative effects at the entrance, in contrast with the negative feedback, where the output causes subtractive effects at the entrance. Contrary to what you may believe, positive feedback is not always desirable, since the “positive” adjective refers to the mechanism, rather than the result.) The non-linear second-order relationship between demographic growth and technological development can be explained according to the following sequence:

•→Increased technological growth, growing the load capacity of the planet → population growth → more people → more potential inventors → acceleration of technological growth → acceleration of the increase of the carrying capacity of the planet → faster population growth → acceleration of the increase of potential inventors → faster technological growth → increasing the capacity of the Earth to support people… and so on. On the other hand, Korotayev’s research has shown that since 1970 the world system never develops hyperbolically; its development diverges more and more from the “regime of inflation” and currently is moving “away from singularity”, rather than “toward singularity.”

Marshall Goldsmith (born March 20, 1949) is an American leadership coach and author of management-related literature. He pioneered the personalized use of the FeedForward as a leadership development tool. The FeedForward assessment tool was created by Marshall Goldsmith with the intention of providing to individuals, teams, and organizations suggestions that help them, in the future, to make a positive change in their behavior. There is a fundamental problem with all types and forms of feedback: focus on the past, on what has already happened, not on the infinite variety of opportunities that could happen in the future. As such, the feedback can be limited and static, rather than dynamic and expansive. The FeedForward of Marshall Goldsmith helps you to predict and to focus on a positive future, not on a frustrated past. In training athletes using ‘feedforward’ (future feedback), the basketball players are taught to see the ball going into the ring and imagine the perfect shot. To give you ideas on how you can be even more successful, the FeedForward evaluative tool from Marshall Goldsmith can increase your chances of success in the future.

Marshall Goldsmith Library:http://www.marshallgoldsmithlibrary.com/

The pluslectic method is converted input, based on the theory of the system and concepts such as positive feedback, the feedforward, and Korotayev front-loading. The dialectical process evolves through concepts, hypotheses, ideas, and where the initial step is always positive (feedforward), accompanied with growth within a system of positive feedback, where the outcome of a positive feedback is one greater amplification which makes a small signal into a major change in the status of the system. Amplification generally grows in exponential systems in a first-order or second-order hyperbolic way.So evolution creates breaks in a positive and fast way, leading to shifts from one system to another system. Such systems are open to differences and are not controlled by negative feedback (which characterizes closed systems), where is the entropy of the system common.

The pluslectic is a philosophical view of how to operate a model of thinking of high civilizations of aliens or humans in the future, which would tell you as plus-humans, if this condition occurs with huge advances in engineering biogenetics, to reduce all the emotions and negative thoughts, where even before any negative events occur, humans would be capable of pre-feeding positively, with a vision of feedforward.

The pluslectic is a concept that is defined as the paradigm for highly developed post-humans, as opposed to the concept of dialecic from the 19th century, and the ideas of the 20th century, still in the generation of the great tales of humankind. Post-modernism and late modernity during the early 21st century are in crisis of change, setting the stage for the birth of new concepts oriented toward the future.

Images by Pedro Villanueva: Image #1 is his symbol for the Pluslectric; Image #2 is his artistic visionary representation of the concept.

NOTES

[1]  The Sublime Object of Ideology (1989). Slavoj Zizek.

[2]  The Antichrist. Friedrich Nietzsche.

[3]. Basement of all the Doctrine of Science (1784). Johann Gottlieb Fitche.

[4] The Phenomenology of Spirit (1807). G. W. Friedrich Hegel.

[5] Capital (1867). Karl Marx.

[6] General System Theory: Foundations,  Development, Applications (1968). George Braziller.

References

Korotayev A., Malkov A., Khaltourina D. Introduction to Social Macrodynamics. Secular Cycles and Millennial Trends. Moscú, Russia Publishers, 2006

Korotayev A., Malkov A., Khaltourina D. Introduction to Social Macrodynamics: Compact Macromodels of the World System Growth. Moscow: Russia Publishers, 2006;

Korotayev A. V. A Compact Macromodel of World System Evolution // Journal of 
World-Systems Research 11/1 (2005): 79–93.

Markov A., Korotayev A.Phanerozoic marine biodiversity follows a hyperbolic trend // Palaeoworld. Volume 16, Issue 4, December 2007, Pages 311-318;

Markov A., Korotayev A. Hyperbolic growth of marine and continental biodiversity through the Phanerozoic and community evolution // Journal of General Biology. Volume 69, 2008. N 3, pp. 175–194

Pedro Villanueva wasborn in Havana, 1974. He graduated from the Academy of Fine Arts in San Alejandro. He writes in an approach to thought known as Pluslectic, which is in line with today’s world and the vision towards the future.

Pedro Villanueva underwent a study bootcamp with FounderSpace in San Francisco USA. He lives in the Chilean Patagonia, Punta Arenas. Building upon the ideas of Vinton Cerf, his research work aims at the creation of an interplanetary network called “InterPlanetNet”, which aims to extend the Internet into outer space. Pedro Villanueva works on the idea of the FaceSpace, a social network of space.

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U.S. Transhumanist Party General Discussion Thread for the First Quarter of 2018

U.S. Transhumanist Party General Discussion Thread for the First Quarter of 2018

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The purpose of this post is to facilitate member comments pertaining to transhumanism and the U.S. Transhumanist Party, which might not specifically fit the subjects of any other post or article on the U.S. Transhumanist Party website. This is the place for members to offer suggestions or converse about any areas of emerging technologies and their political, moral, societal, cultural, and esthetic implications. The general discussion thread is also an ideal location to suggest or propose platform planks that may be considered for future platform voting.

The U.S. Transhumanist Party will endeavor to open one of these general comment threads per quarter. This comment thread pertains to the months of January, February, and March 2018.

Type in your comments below. Please note that, to protect against spambots, the first comment by any individual will be moderated. After passing moderation, a civil commenter should be able to post comments without future moderation – although we cannot guarantee that the technical aspect of this functionality will work as intended 100% of the time.

Moon Ribas – Seismic Sense

Moon Ribas – Seismic Sense

Moon Ribas


 

It’s 2018, another year in this shared reality of ours. We’ve come a long way, perfecting our technological prowess as we continue our evolution into the post-human.

There are cyborgs out there. In fact, most of us are pretty much cyborgs at this point. However, it is indeed likely only some of us are truly beginning to tap into that potential.

Moon Ribas is known to the world as the Catalan avant-garde artist and a cyborg activist. Moon Ribas is one of those cyborgs, an example of the elegantly functional relationship between human and machine.

With an online seismic sensor directly implanted above her left elbow, she is able to perceive the vibrations of nearby earthquakes via data from a custom iPhone app that consolidates seismic activity from geological monitors around the world. Ribas then transposes this ‘seismic sense’ into bodily movement in her graceful performance known as Waiting for Earthquakes or into sound in her piece Seismic Percussion.

With the subdermal implant, Moon Ribas is able to further push the boundaries of perception and experience by means of personal augmentation. During the devastating 7.8 earthquake that struck Nepal in 2015, Ribas was awoken by a wave of vibrations in the middle of the night. She recalls it as the most peculiar of sensations, also describing it as her second heartbeat as she is able to empathize with the people experiencing the quake. This has lead her to advocate for a better understanding of the natural phenomena so that us humans may be able to better adapt to our own planet’s movements.

Along with Neil Harbisson, another fellow cyborg, they have co-founded the international organization Cyborg Foundation in the pursuit to help all the rest of us become post-human and to protect our rights as post-humans.

It is the insatiable creative thirst of humans like Moon Ribas that slowly pushes us to the inevitable brilliant future that is to come. 

Moon Ribas is an artist and activist. More of her beautiful work can be found on her site.

~ Emanuel Iral, Director of Visual Art, U.S. Transhumanist Party, January 11, 2018 

Looking Back at 2017: A Year in Rejuvenation Biotechnology – Article by Nicola Bagalà

Looking Back at 2017: A Year in Rejuvenation Biotechnology – Article by Nicola Bagalà

Nicola Bagalà


 

Editor’s Note: In this article, Mr. Nicola Bagalà highlights various events of rejuvenation biotechnology in the year 2017.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 11, 2018

Winter kick-off

This year has been pretty intense, with a lot going on both at LEAF and in the rest of the community. January saw the launch of the LEAF website, shortly followed by both the Lifeboat Foundation and Trust me – I’m a biologist partnering with us. Given that it’s been only a year, we’re amazed at how enthusiastic and supportive the community has been—and how fast it has grown, with nearly 30,000 Facebook followers late in December! We’re also very grateful to our friends at Fight Aging! for their encouragement, support, and appreciation for our work, including honoring us by featuring it on their website!

In February, the CellAge campaign launched in late 2016 concluded successfully, also thanks to the matching fund put together by Longecity. That’s also when LEAF President Keith Comito met Mikhail Batin to discuss the Russian initiative Open Longevity and when Series A funding was announced for LYSOCLEAR, a LysoSENS-based approach to treating macular degeneration.

An eventful spring

The Lifespan Heroes campaign was launched in the spring, and thus far, it has greatly helped us carry out our activities, especially in terms of web development—so thank you to all our generous donors!

In the spring, we also started our advocacy projects with global policymakers. During April 10-15, LEAF Board Director Elena Milova attended a training program conducted by the International Institute on Ageing (INIA) in Saint Petersburg, where she met and interviewed INIA director Dr. Marvin Formosa and former Head of the UN Programs on Ageing Dr. Alexandre Sidorenko.

Later in April, the SENS Research Foundation announced a collaboration on a cellular senescence project with the Buck Institute for Research on Aging.

The month of May was busy with conferences and networking; at the International Longevity and Cryopreservation Summit in Madrid, Elena Milova had the opportunity to interview life extension advocate Didier Coeurnelle, London Futurists Chair David Wood, Dr. Jose Luis Cordeiro, Senior Scientist at CONICET Dr. Rodolfo Goya (we hope to support his studies related to Yamanaka factors in 2018 via crowdfunding at Lifespan.io), and SRF’s Chief Science Officer Dr. Aubrey de Grey. Elena herself gave a talk about effective life extension advocacy methodologies; LEAF board member Paul Spiegel also gave a talk about the need for society to adapt to longer lives. In Paris, the International Cell Senescence Association (ICSA) held a conference discussing senescence triggers, physiological functions of senescence, and pathologies and therapies. We announced the event here.

Our Journal Club series was also launched at the end of May, for a total of eight Journal Club episodes this year, which you can watch here. The Journal Club is a monthly science show on which Dr. Oliver Medvedik hosts guests, and this show is supported by our patrons, the Lifespan Heroes. We broadcast this show live to our Facebook Page every month, where we invite the audience to ask questions and join in with the discussion.

Summer news

In the summer, LEAF and MMTP co-hosted a panel featuring Dr. Alexandra Stolzing, Dr. Aubrey de Grey, and Dr. Oliver Medvedik. This live broadcast included discussions about funding, research progress, and advocacy, providing some interesting insights into the field. They were joined by Alen Akhabaev, one of the project donors who supported the MMTP project on Lifespan.io, as well as Steve Hill and Elena Milova from the MMTP and LEAF.

The AgeMeter campaign was launched on Lifespan.io by Elliott Small in July, and in August, we celebrated the first birthday of our crowdfunding platform—you could say Lifespan.io’s birthday present was the MouseAge campaign launched shortly thereafter. The campaign was successful, and the MouseAge app is now ready and expected to be launched shortly. The use of AI is trending more and more in the field of aging research, so this app is certainly only one of many that will be employed in the future.

A great autumn

The autumn has been, without doubt, the busiest time of the year. The Undoing Aging conference was announced by the Forever Healthy Foundation in September, as was a series of small-scale human senolytic pilot studies by Betterhumans. Almost at the same time as the AgeMeter campaign reached 100% of its goal, Dr. Aubrey de Grey joined our SAB (Scientific Advisory Board), shortly followed by Dr. Robert Shmookler Reis. At this time, SRF and the Spiegel Lab launched a collaboration on developing monoclonal antibodies against glucosepane.

September also saw the Basel Life 2017 conference held in Basel, Switzerland, where Dr. Alex Zhavoronkov chaired the Artificial intelligence and block chain in healthcare and the Aging & drug discovery forums. Insilico Medicine’s Young.AI aging-rate tracking app was officially announced at this conference.

Juvenescence by Jim Mellon and Al Chalabi—a thorough, investor-focused introduction to the science of aging and the world of rejuvenation biotech—was published on September 25. LEAF has published two reviews of the book, which you can read here and here.

Open Longevity ICO, a Russian project focused on conducting clinical trials of geroprotective therapies and introducing diagnoses of aging into clinical practice, was launched in September. It is currently entering the second phase of pre-ICO, and we wish Anastasia Egorova’s team good luck.

In October (which is traditionally considered the Longevity Month) we launched the #IAmTheLifespan campaign, inviting all our supporters to make videos describing what brought them to join our cause, and you can watch some of them here. To help out MouseAge, and for Inktober 2017, our volunteer Laura Weston launched a fundraiser offering her beautiful artwork as a reward for donors.

The Pathways to Healthy Longevity 2017 conference was organized on October 15th by Dr. Ilia Stambler, a famous longevity activist, in Bar Ilan University (Israel), with Prof. Nir Barzilai and Prof. Haim Cohen as key speakers.

In late October and early November, the popular YouTube channel Kurzgesagt published End Aging? and Cure Aging?, which were both created with help from the Lifespan.io team. We saw overwhelming support from old and new members of the community, showing that healthy life extension is much more popular with the public than one might think.

As MouseAge reached and surpassed its goal, news started to spread that WHO was planning to leave healthy aging out of the general programme of work 2019-2023; thanks to the advocacy efforts of the community, though, WHO has received plenty of feedback on the issue and may hopefully reconsider.

During November 8-10th, the TransVision conference was held in Brussels. It was organised by Didier Coeurnelle, the head of HEALES, the Healthy Life Extension Society. Among its other objectives, the Technoprogressive declaration presented at the conference mentions the defeat of aging; it’s good to see that this objective is now considered to be of primary importance by a growing number of organisations.

During December, LEAF took part in Project4Awesome; many amazing videos were made to support us, and we’re really grateful to the community for that. It was a truly beautiful display of generosity, and not the only one; thanks to many fantastic donors, including the mysterious Pineapple Fund creator, the SENS Research Foundation has smashed its funding goals for the year. You can read more about the December highlights here.

Coming up in 2018

In 2018, we will be working towards creating more major media collaborations with awesome content creators to spread further awareness about the problem of aging and the upcoming advent of rejuvenation biotechnologies.

Our web development team will be, and in fact already is, working on improving the overall user experience of our followers and scaling our systems up to meet the needs of a larger user base; we experienced a significant growth in this sense after our collaboration videos with Kurzgesagt were published, and we’re most definitely looking forward to this happening again!

Our Journal Club will, of course, continue discussing and providing commentary on the latest aging research news in the company of special guests from the biogerontology world. More livestream events are in the cards too, so keep an eye on our Facebook page, and subscribe if you haven’t already!

As the community grows larger, so does the need to establish and develop regional presences; our next objective will be starting the Russian chapter of LEAF to engage with a wider audience. Aging is a global problem, so the more communities and audiences we can get involved in the fight against age-related diseases, the better.

LEAF will naturally take part in as many events in the healthy longevity world as possible to keep our readers in the loop. A big must is definitely the March 15-17 Undoing Aging conference in Berlin, Germany, as is the April 22-26 Interventions to Extend Healthspan and Lifespan conference in Kazan, Russia. There will certainly be much exciting news to share, so stay tuned!

The Eurosymposium on Healthy Ageing—a scientific conference organized by the European aging research advocacy group HEALES—will be held in Brussels on November 8-10. It is likely that at least a few of the LEAF team will be at the event, and it is sure to be an interesting one.

Finally, of course, more exciting crowdfunding projects are in the works!

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

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Libella Gene Therapeutics


ORLANDO, Fla.Jan. 10, 2018 /PRNewswire/ — Libella Gene Therapeutics LLC will conduct an OUS (outside the United States) clinical trial in Cartagena, Colombia, using gene therapy to reverse age-related diseases, starting with Alzheimer’s. Unlike traditional drugs, which tend to be taken for months or years at a time, gene therapy interventions are intended to be one-off treatments that tackle a disease at its source, repairing faulty DNA and allowing the body to fix itself.

Every day 228 Americans die from Alzheimer’s disease, and there is currently no known treatment or cure. Gene therapy offers the ability to permanently correct a disease at its most basic level, the genome, and could offer cures for many conditions that are currently considered incurable. According to Dr. Bill Andrews, the scientist leading the study, “Human telomerase reverse transcriptase (hTERT) is an enzyme whose expression plays a role in cellular aging and is normally repressed in cells, resulting in progressive shortening of telomeres. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.”

By inducing telomerase, Dr. Andrews and Libella Gene Therapeutics hope to lengthen telomeres in the body’s cells. The clinical trial will treat a limited number of patients using the gene therapy treatment, which has been demonstrated as safe, with minimal adverse reactions in over 186 clinical trials.

Dr. Andrews has been featured in Popular Science, on the “Today” show and in numerous documentaries on the topic of life extension. As one of the principal discoverers of both the RNA and protein components of human telomerase, Dr. Andrews was awarded second place as “National Inventor of the Year” in 1997. He earned a Ph.D. in molecular and population genetics at the University of Georgia in 1981. He has served in multiple senior science and technology roles at leading bioscience corporations. Dr. Andrews is a named inventor on over 50 U.S.-issued patents on telomerase and is the author of numerous scientific research studies published in peer-reviewed scientific journals.

On why the company decided to conduct its clinical research project outside the United States, Libella Gene Therapeutics president Dr. Jeff Mathis said, “Traditional clinical trials in the U.S. can take years and millions — or even billions — of dollars. The research and techniques that have been proven to work are ready now. We believe we have the scientist, the technology, the physicians, and the lab partners that are necessary to get this trial done faster in Colombia.”

The clinical trial is prepping to begin in the first quarter of 2018 and will be conducted at MediHelp Services Clinic in beautiful and tourist-friendly Cartagena, Colombia. The state-of-the-art facility has hosted international public figures including athletes, celebrities and politicians. Dr. Javier Hernandez, MediHelp’s medical director, will oversee the trial.

Colombia’s clinical research regulation is friendly to gene therapy trials, with one of the fastest approval times in Latin America for this kind of research. The trial’s clinical study design; regulatory, operation and logistical support; project management; statistical analysis; and study monitoring services will be provided by LATAM Market Access Inc., a Florida-based clinical research company.

About Libella Gene Therapeutics LLC 
With a mission to reverse aging and cure all age-related diseasesstarting with Alzheimer’sLibella Gene Therapeutics has exclusively licensed the AAV Reverse (hTERT) transcriptase enzyme technology from Sierra Sciences and Dr. Bill Andrews. More information at www.libellagenetherapeutics.com.

About LATAM Market Access Inc.
Dedicated to helping innovative life science companies gather cost-effective clinical data at leading research institutions, the company provides clinical study design; regulatory, operational and logistics support; project management; statistical analysis; and study monitoring services. More information at www.latammarketaccess.com.

 

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà explains to us the terms “rejuvenation”  and “immortality” and how they should not be construed to mean one and the same.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 10, 2018

When doing science, it is crucially important to have clear, unambiguous definitions. These definitions must be firmly established to avoid confusion and misunderstandings and possibly to prevent people from going around telling everyone that you’re working on something that you’re actually not.

The I-word

It’s not uncommon, especially for outsiders of a given field, to use an inappropriate word to indicate a more complex concept than the word itself conveys—maybe because they think that the two are close enough or possibly because they just don’t see the difference.

For this reason, it’s likely that each field has its own unspeakably profane word; in the field of rejuvenation, that word is the dreaded I-word: immortality.

Before I explain why it is a dreaded word, it’s important to define what the heck it even means. Now, of course definitions are entirely arbitrary, and the same word could mean a different thing to a different person; but if we go with the most intuitive, commonly accepted meaning of “immortality” when nothing else is specified, then we can safely say it describes the quality of someone who cannot die. In other words, it refers to an immortal being could not be killed or die in any way, even if it wanted to. Just like people today who would like to live for an indefinitely long time (like me) are forced to eventually die by aging and are thus stuck without a choice (at least until we figure rejuvenation out), a hypothetical immortal being would be in a similar situation, with no choice to terminate its life because its immortality would force it to live forever. This brief article explains the issue very nicely and concisely.

Now, the way I approach life, immortality wouldn’t be all that bad, because I am skeptical that I’d ever have a reason to want to die. Still, I appreciate that I might be wrong, so if I could choose and wanted to play it really safe, I’d opt for an “immortality switch”; as long as it is on, you’re immortal; if and when you get tired of life, you flip it off and you become mortal again, free to get rid of your own life however you see fit.

Unfortunately, an immortality switch is just as improbable as immortality itself. Think about it: to be immortal, your chance of ever dying of any cause at all should be exactly zero. There’d be no gun, no disease, no poison, no amount of air taken out of your lungs, no stellar explosion capable of terminating your existence. The inner workings—biological or not—keeping you alive should be indestructible, able to withstand forces of any magnitude and keep going under any possible circumstance (including running out of energy). Even without dragging the fabled heat death of the universe into the mix, it’s difficult to imagine how any of this could ever be possible—let alone a switch turning this unlikely ability on and off.

What’s the difference?

I’m not going to go as far as to say that the above is completely impossible; I was trained to make such bold claims only when I can prove them, so I’ll just say that, to the best of my knowledge, this sort of immortality appears to be exceedingly unlikely.

Now, whether immortality is possible or not is an intriguing question, but it is decidedly off-topic in the field of rejuvenation, because rejuvenation is not immortality. If a universal antiviral drug able to wipe the floor with every conceivable virus existed, you wouldn’t call it an immortality drug, because right after leaving the doctor’s office where you got your miracle shot, a grand piano might happen to crush you after a 50-story free fall, and the antiviral drug wouldn’t be especially effective against that particular cause of death. Similarly, rejuvenation would save you from death by age-related diseases, but not by falling grand pianos, sadly.

Yet, both people and the media keep talking about “curing death” and “immortality pills” when the actual topic is rejuvenation biotechnology; this is a cause of particular annoyance to Dr. Aubrey de Grey, whose pioneering work is constantly called an “immortality quest” and similar things. Since immortality reasonably seems a pipe dream and is laden with all sorts of ethical issues and concerns, whether justified or not, this results in a gross misrepresentation of the entire field and a lot of unwarranted bashing of completely legitimate medical research whose only fault is that it aims to prevent the diseases of aging rather than just coping with them.

The same story is true of negligible senescence. If a successful rejuvenation platform were implemented, people would still age biologically, but we would have therapies capable of undoing such aging. Through periodic reapplication of these therapies, the hallmarks of aging would always be kept well below the pathology threshold. In other words, we would still senesce (that is, age), but our level of senescence would stay negligible—that’s where the term comes from. Yet, many people keep calling negligible senescence immortality just like they do rejuvenation biotechnology, whether deliberately or by genuine mistake, thereby providing an excellent strawman for needy critics to beat. This is why the I-word is dreaded in this field, by the way.

Negligible senescence is the expected result of truly comprehensive rejuvenation biotechnologies, and yes, if we got there, our healthspan would be vastly increased, and consequently, so would our lifespan; if you were in perfect health for longer than, say, 100 years, it is a disarmingly trivial consequence that you would live for longer than 100 years. However, whether a negligibly senescent person then lives on forever or not, or ten thousand years from now, someone beats the odds and comes up with a fancy immortality switch, is an entirely different matter that is beyond the scope of the field of rejuvenation biotechnology. Speaking of which, let me reiterate once more what its actual scope is: to eradicate age-related diseases. All the rest, whether consequential effects or downright made-up rubbish, is just unnecessary embroidery.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

A Review of Immunosenescence – Article by Steve Hill

A Review of Immunosenescence – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Steve Hill discusses some of the reasons for the decline of the immune system.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 9, 2018

Immunosenescence is the age-related decline of the immune system. The reason why our immune systems start to fail and weaken as we age is not fully understood, and, indeed, there are a variety of hypotheses as to why this happens.

Inflammaging

Inflammation certainly plays a role in this process, and it is well documented that inflammation has a considerable effect on immune cells such as macrophages, causing them to become dysfunctional and stop cleaning house. This is in line with the proposed concept of “inflammaging”, which describes an ever-increasing chronic background of inflammation from sources such as senescent cells, cell debris, and changes in the gut microbiota. This inflammaging then drives immune system dysfunction, which then creates more inflammation, continuing a downward spiral.

We recently learned that inflammation can cause problems with weight control by causing nerve-associated macrophages to stop signaling fat cells to release their stored energy[1]. We also know that macrophage dysfunction occurs in other tissues due to inflammation, and so it seems clear that inflammation plays at least a partial role in immune system decline.

Cellular Senescence

Some research suggests that the immune system declines due to its cells becoming senescent, just as other cell populations do. Over time, our cells reach their maximum number of divisions, or they are damaged and enter senescence and destroy themselves via apoptosis, a kind of programmed self-destruct sequence.

However, sometimes these cells resist apoptosis and cling on to life, but in doing so, they prevent fresh cells replacing them while generating inflammatory signals that cause nearby cells to become dysfunctional, too. It is proposed that the immune system experiences the same senescence as our other cells, leading to immune system failure.

Stem-cell depletion

Another player in immune system decline is stem-cell depletion; for example, the thymus begins to shrink from an early age and eventually stops producing new T cells to help defend us from invading pathogens. The production of T cells is facilitated by thymic stem cells, which are gradually depleted over our lifetime, and eventually, we have so few T cells that we cannot fight off diseases such as flu and pneumonia, which often kill the elderly. Some attempts are currently being made to rejuvenate the thymus and have enjoyed some success.

A review of immunosenescence

It is likely the case that immunosenescence is a combination of all of these proposed things and more, and each plays a role in the resulting decline of our immune systems as we age. When it comes to establishing the exact chain of events that leads to immunosenescence, it will take reversing each of those causes to see what happens.

Today, we wanted to bring your attention to an open-access paper that reviews the current knowledge of immunosenescence and provides a good introduction to the topic[2].

Conclusion

Developing the therapies that target the aging processes directly is likely the most expedient path to understanding immunosenescence, as these therapies will give us the tools with which to discover what drives the process. Approaches such as thymic rejuvenation or creating a replacement thymus, replacing lost stem-cell populations such as hematopoietic stem cells that create all immune cells, removing overspecialized immune cells, and removing senescent cells are all valid approaches towards discovering how immunosenescence works.

Our knowledge is growing rapidly by the passing month, and more and more is being understood about the aging processes and how we might directly target them to prevent or reverse age-related diseases. It is almost certain that medicine is going to change dramatically in the next decade or two as our understanding grows.

Literature

[1] Camell, C. D., Sander, J., Spadaro, O., Lee, A., Nguyen, K. Y., Wing, A., … & Rodeheffer, M. S. (2017). Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature, 550(7674), 119-123.

[2] Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and Molecular Allergy, 15(1), 21.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

How Humans Learned to Stop Worrying and Love Death – Article by Jaeson Booker

How Humans Learned to Stop Worrying and Love Death – Article by Jaeson Booker

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Jaeson Booker


Okay, for this, we have to go back. Way, way back. Before we made history, before we made civilization, before we humans did a lot of things. We may not have even been fully human at the time this happened. But at some point, we became self-aware. This process probably took some time, I doubt it was an “AH-HA!” moment that suddenly changed everything. But we then had the ability to comprehend ourselves: to view ourselves as an independent entity, separate from others, and could reflect on this. And, amid all of this self-revelation, with so many new existential possibilities, we got mauled by a second revelation: we saw other people dying. They got old, they got sick, they stopped moving, and then other animals and bugs started eating them (or, perhaps, we were the ones doing the eating; see “Cannibalism Normal for Early Humans?” by John Roach, National Geographic News, April 10, 2003). And we acknowledged that they were like us, that we one day would meet the same fate.

Well… that sucks. All of this possibility, all of these questions, a whole world to explore, and it turns out we’ll cease to exist before we get to experience even a small fraction of it. Damn. Well… what can be done of it? This question, as soon as humans figured out more advanced communication, was probably many times on their minds. From here, there seem to be three routes.

The first and most depressing, yet also the most pragmatic at the time: accept it and enjoy the time you have. “S**t happens. There ain’t nothin’ you can do about it.” This prospect was probably hard for many to face, causing them to try not to think about it instead (a habit many people still have today). But at the same time, it was probably the only realistic-seeming prospect for some time. Death happens. What can be done of it? No use feeling bad about something that can’t be controlled. Are you going to throw a fit every time it rains?

The second, and easiest to adopt: telling yourself it’s not true. Acknowledging you and everyone you love won’t exist one day is a tough pill to swallow, a pill many don’t want to take. But if nothing can be done about it, the only way around the pill is either ignoring death or believing differently. Over time, believing differently got easier and easier. It probably wasn’t done intentionally, but any idea we might not die when we shed our mortal coil probably spread faster than smallpox. Flowers came back every spring, after ‘dying’: where did you go? Trees went stark and bare, but came back to full health in the spring. How do we know this doesn’t happen to humans? Perhaps we were in our winter, and one day, human spring would come, and all the dead humans would sprout back up like daisies.

Over time, the resurrection pill probably went from easy-to-swallow to a-bit-more-difficult-to-swallow. Generations passed, with the stories being told, but human spring never came. We understood that seeds were the reason plants came back, and that it wasn’t an actual resurrection after all. And if you chopped-down a tree, it didn’t turn green next year. This is all speculation, of course, but at some point humans invented a concept that fixed this: the soul pill.

Ah, the soul, man’s best friend. Suddenly the body had nothing to do with all of those things people really cared about. All of those things humans tied so closely with their identity: emotions, reason, consciousness itself, all of these things the soul had covered for us. You could get pierced by a sword, fall off a cliff, be burned in a forest fire, but none of these perils could kill a soul. Whatever happened, no matter how bad things got, you were, ultimately, okay – because your soul would live on. To quote the Iron Giant: “Souls don’t die”.  Ah, death, thou shalt die at last.

But after a while, things started to change. We were starting to learn a lot, and a bunch of the earlier myths were turning-out to be false. Lightning wasn’t the wrath of any deity, the sky didn’t lead to any spirit world, humans weren’t created by anything but instead evolved, and a whole lot of the things we associated with “the soul” could be explained by a thing called a brain. Worse still, when this brain was changed, so did our personality. (See the Wikipedia entry on Phineas Gage.) This was depressing for many who saw the signs. And that soul pill, once so easy to swallow, was becoming harder and harder to get all the way down.

Which brings us to where you walked in. Many of us are still having issues with that soul pill, but many still don’t want to swallow that “we’re all gonna cease to exist” pill. For those who rejected the soul pill, many instantly grabbed a glass of water and hurriedly swallowed the other pill. They were proud of swallowing that tough pill, and annoyed with those struggling with the soul pill for not being brave-enough to do what they did. They found new ways to discover meaning, despite knowing they would die. Death was natural. Population had to be kept under control. They could live on through other means: their children, their legacy, the people they helped. The last thing these tough-pill-swallowers wanted to do was regurgitate something that had been so hard to get down in the first place. Which is why both types of pill-takers really hate the third pill.

The third pill: actually doing something about it. This solution had started around the time of the other two, but after a brief flare-up of popularity, had quickly died down due to failing to produce any results. Magic, the philosopher’s stone (the dream of the alchemists), blood sacrifices, breathing the air of virgins, and cannibalization of the young: these were all very embarrassing failures of this pill. After these blunders, no one really wanted anything to do with it anymore. And this is how things stayed for a long time. But even though the mentality toward this solution has stayed relatively the same for a long time, it’s potential was slowly changing. We were starting to understand how the body worked, and improve people’s health. We learned we were made up of these tiny things called cells, and that those cells were manufactured using even smaller things called DNA and RNA. And with all of this new-found knowledge, many were starting to wonder if discarding the third pill might have been a bit premature.

Up until very recently, the response has not been very nice to advocates of the Do-Something-About-It pill. And even today, there are many who call such advocates insane, immoral, greedy, and anything else you that’s meant to sound bad or misguided. The advocates of the soul-pill and the tough-pill could finally agree that this other pill had to go. Religions declared such aspirations evil and against God’s will. Scientists worked hard to separate themselves from these advocates as much as possible, not wanting to be lumped in with what sounded to many like some sort of icky cult.

So, the swallowers of the first two pills march forward, parading ideas of death and aging being natural, that seeking anything else is wrong and selfish, and we should just accept our situation. It is these two pills that have enabled people to justify a holocaust that is occurring every day – a holocaust that will one day claim us all, unless the third pill is ever swallowed and digested properly by humanity. Aging has killed more than all wars, famines, and plagues combined, yet most march onward, without making any attempts to halt it. Governments invest in fighting cancer, heart disease, and countless other ailments—ignoring the underlying cause of most of these problems, which is aging itself. Every year, there are drives for charities to fight different cancers, entire months and hues devoted to some (See “Pink porta-potty fundraiser aimed at flushing breast cancer“, CBC News, October 2, 2017), yet none toward combating aging. People stake trillions of dollars toward remedies to make them look younger, but almost none to aiding the effort of actually making them younger. They plan out their wills, their life insurance, and their funerals, but ignore opportunities to preserve themselves (for instance, cryopreservation, as offered by the Alcor Life Extension Foundation or the Cryonics Institute) for a chance to keep living, even if it is more affordable than they think.

But, despite the opposition, this solution has been making progress. We have seen progress in stem cells (“Anti-aging stem cell treatment proves successful in early human trials” by Rich Haridy, New Atlas, October 23, 2017 ), biotechnology (“A Silicon Valley scientist and entrepreneur who invented a drug to explode double chins is now working on a cure for aging” by Nikhil Swaminathan, Quartz, January 6, 2017), and machine learning used to better understand the aging process and how to treat it (“Artificial Intelligence uncovers anti-aging plant extracts” – Press Release by Insilico Medicine, October 31, 2017). The third pill is getting more and more enticing. Many older people, having swallowed one of the first two pills decades ago, have no desire to change their existential outlook now. But many younger ones, those who have not yet chosen a pill, and finding the other two inadequate, are starting to wonder if the third pill is for them. Time will tell which pill will ultimately win out, if any, but for now, for the first time ever in human history, the Do-Something-About-It Pill has an actual chance to shine and show what it is truly capable of.

Jaeson Booker is a software development engineer who has worked as a journalist. He earned a Bachelor of Arts (BA) degree in Political Science from Salisbury University, a Bachelor of Applied Science (BASc) degree in Molecular Biology from the Texas A&M Univerisity in Corpus Christi, and a Master of Business Administration (MBA) degree from Wilmington University.

The Link Between Cellular Senescence and Cellular Reprogramming – Article by Steve Hill

The Link Between Cellular Senescence and Cellular Reprogramming – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Steve Hill discusses the link between Cellular Senescence and Cellular Reprogramming.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

            ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 8, 2018

The reprogramming of cells is a well-established technique in medicine and has been for over a decade now. It allows the en masse creation of patient-matched cells and is the basis for multiple current therapies.

Cellular Senescence and Cellular Reprogramming share mechanisms

Induced pluripotent stem cells (also known as iPS cells or iPSCs) can be created directly from adult cells. The iPSC technology was pioneered by Shinya Yamanaka, who demonstrated in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells[1]. These factors are Oct4, Sox2, Klf4, and c-Myc (OSKM), or as many call them, the Yamanaka factors.

Today, we have a new paper that discusses how induced pluripotency and cellular senescence, two of several possible cellular states, share similarities[2]. It is likely no surprise that the two states are closely related and that some of the mechanisms for one process are shared by the other. It appears that certain key signaling molecules are important in determining both cell fate and senescence.

Controlling cell behavior in living animals

As our understanding of guiding cell fate grows rapidly by the passing year, it has huge implications for therapies that seek to control cellular activities and encourage certain types of cells to be created. Research is now starting to move beyond the petri dish and to where cells are being programmed in situ in living animals.

In 2013, the Hallmarks of Aging proposed that epigenetic changes are a primary reason we age, but, at the time, the evidence in living animals was lacking[3]. All this changed in late 2015 when researchers induced pluripotency in living animals using the OSKM reprogramming factors, in much the same way as iPSC technology creates on-demand cell types outside the body. In this case, they only very briefly induced OSKM so that the aging markers in cells were reset but not long enough to cause the cells to revert to a developmental state.

The results of this first attempt to reprogram cells in living animals resulted in the cells of the mice becoming functionally younger in many ways and increased their healthy lifespan[4]. These results lend yet more support for the hypothesis that epigenetic alterations are one of the reasons we age and that reversing those changes is a path to maintaining health and tissue function as we age. A number of research teams are now exploring cellular reprogramming in living animals with a view to translating this to humans. We discussed the findings of this paper during our monthly Journal Club here.

Conclusion

This paper may be of interest to those wishing to delve deeper into the world of cell fate and understand the connection between cellular senescence and induced pluripotency. This builds on the knowledge we already have, and it is not difficult to imagine a time in the near future when we will have a very high level of control over our cells via reprogramming techniques.

If the hypothesis of epigenetic alterations being one of the causes of aging turns out to be correct, then that would be a real game changer. We are likely not too far off from determining if this is the case or not, and we may have the answer in the next few years, given the current pace of progress.

Literature

[1] Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 126(4), 663-676.

[2] Mosteiro, L., Pantoja, C., Martino, A., & Serrano, M. (2017). Senescence promotes in vivo reprogramming through p16INK4a and IL‐6. Aging cell.

[3] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[4] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Long Interview with Dr. Aubrey de Grey by Ariel VA Feinerman

Long Interview with Dr. Aubrey de Grey by Ariel VA Feinerman

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Ariel VA Feinerman
Aubrey de Grey


This interview was originally published here

What is ageing? We can define ageing as a process of accumulation of the damage which is just a side-effect of normal metabolism. While researchers still poorly understand how metabolic processes cause damage accumulation, and how accumulated damage causes pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring the previous undamaged — young — state of an organism, we can really rejuvenate it! It sounds very promising, and so it is. And for some types of damage (for example, for senescent cells) it is already proved to work!

Today in our virtual studio, somewhere between cold, rainy Saint-Petersburg and warm, sunny Mountain View, we meet a famous person. I hope everyone knows Aubrey de Grey — the man who fell to Earth in order to change our vision of ageing, to fight with and to finally save us from it! For those of you who are not familiar with him, here is a brief introduction.

Dr. de Grey is the biomedical gerontologist who researched the idea for and founded SENS Research Foundation. He received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. Dr. de Grey is Editor-in-Chief of Rejuvenation Research, is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organizations. In 2011, de Grey inherited roughly $16.5 million on the death of his mother. Of this he assigned $13 million to fund SENS research.

I will not ask Dr. Aubrey de Grey any of those stupid questions that journalists usually annoy him with, about his appearance, overpopulation and so on. Instead, we will talk about science and engineering that will rejuvenate our bodies and allow us to be healthy and live longer (I mean really much longer). Because of the recent breakthroughs in many fields, from bionics and applied physics to molecular biology and regenerative medicine, it can (and, I am sure, will) be sooner than you think.

Interview

Feinerman: Hello, Dr. de Grey!

de Grey: Hi — thanks for interviewing me.

Feinerman: In 2012, I read an article by David Sinclair, where he described reversing the loss of mitochondrial function in old mice cells by using NAD+. I felt this was a major change. The past five years have been remarkable! Now every day I read new articles and news about age reversal. In three years, there has been the creation of a few dozen new bioengineering companies whose main goal is to reverse ageing. Billions of dollars are now invested in this area. I believe we will remember 2016–2017 as the most important years. Do you share this feeling?

Note: The first Phase 1 human ageing reversal trials (GDF, Myostatin) will be in a year or two, and George Church discusses how to affordably rejuvenate the whole body! The first version of human CRISPR/Cas9 was created in 2013, and now it is ready for use. In 2015 eGenesis began to work on pigs for xenotransplantation and now they claim they have created retrovirus-free pigs! In 2016 Juan Carlos Izpisua Belmonte has reprogrammed cells by using special factors and reverted back the biological clock in live mice. And this is only a tiny fraction of news!

de Grey: Yes and no. Yes, in the sense that there are indeed more and more exciting breakthroughs being made in the lab — and of course I am very proud that SENS Research Foundation is responsible for some of them. But no, in the sense that there is still a terribly long way to go; we need to fix a lot of different things in order to get rid of ageing, and for some of them we are still at a very early stage in the research.

Feinerman: George Church said that his lab is already reversing ageing in mice and that human applications may only be a few years away. He said: “We have 65 gene therapies that are being tested in mice and larger animals. If they go well, we will go straight into human trials.” Church predicts that age reversal will become a reality within 10 years as a result of the new developments in genetic engineering. However, he warns that age reversal at a molecular level doesn’t necessarily mean that everything else rejuvenates. No one knows what age reversal will mean for humans. Anyway, all that sounds very promising?

de Grey: George is exactly right, both in his urgency and optimism, and also in his caution about how much we don’t yet know.

Feinerman: You have really changed the world’s opinion, but now you are behind the scenes. I regularly read about new breakthroughs in the news while I don’t see much about your work, even though research in SENS is more fundamental in general! When I went to the SENS web page, I was wondered how much you do. This seems like an injustice and can it be fixed?

de Grey: Oh, I’m still quite prominent — I’m still doing just as many talks and interviews as ever. If, to some extent, my contributions are now being overshadowed by other people’s breakthroughs, that’s a good thing! I have always said that my goal is to advance the crusade far enough that I can retreat into glorious obscurity because others are doing my job better than me.

Feinerman: For many people, their appearance is as important as their health. When you say that SENS 1.0 panel of therapies can rejuvenate people from 60 to 30, do they look like 30? Or can they look like 30?

de Grey: Definitely yes. When we thoroughly rejuvenate the inside of the body, the outside is the easy part!

Feinerman: Can we now say that biomedical engineering and biotechnology have entered an exponential phase?

de Grey: I think we can just about say that, yes. It’s very exciting.

Ending Aging Revisited

Feinerman: Your famous book Ending Aging was published 10 years ago. Would you like to make a new version?

de Grey: I probably should, at some point, but it’s not a priority, because the overall approach that we described in that book has stood the test of time: we have made plenty of progress, and we have not come across any unforeseen obstacles that made us change course with regard to any of the types of damage.

Note: If you have not read Ending Aging yet, I suggest you to do it as soon as possible, and to be more comfortable with the ideas we are discussing below, I highly recommend you to read the short introduction to SENS research on the SENS Research Foundation web page. Also, if you are interested in recent news and up-to-date reviews about [anti]ageing and rejuvenation research, the best place to look for is the Fight Aging! blog. Finally, if you are an investor or just curious, I highly encourage you to take a look at Jim Mellon’s book Juvenescence.

Feinerman: You look for bacteria who feed on dead animals to find enzymes capable of breaking glucosepane. Do you consider insects? They can eat nearly everything — and much faster!

de Grey: Nice idea, but we’re looking for a different sort of eating. Insects eat stuff and excrete what they can’t digest, just like us. Bacteria are much more versatile.

Feinerman: Many insects have no special enzymes; instead, they rely on bacteria who do all the work. In any case they are a nice place to look for the enzymes!

de Grey: Yeah, well, not really. Insects have commensal bacteria, yes, but so do we. In general, though, bacteria that are living freely in the environment are more diverse than those in the guts of animals.

Feinerman: How do you find useful bacteria?

de Grey: We are using a “metagenomic” strategy for identifying enzymes that can break glucosepane: we take standard E. coli bacteria, we break one or two of their genes so that they become unable to synthesise one or another chemical (in this case typically arginine or lysine) so that they need to take it up from their surroundings, and then we add random DNA from the environment (which could come from any bacteria, even unculturable ones) and add bits of it to the E. coli. Very occasionally the new DNA may encode an enzyme that breaks glucosepane, and if so, the bacteria will grow even without any arginine or lysine in the environment, if (but only if) we give them glucosepane instead and they break it to create arginine and lysine.

Feinerman: In your book you proposed Whole-body Interdiction of Lengthening of Telomeres (WILT) — the removal of telomerase in all cells in order to prevent cancer and reseed the stem-cell population regularly. Is there any success in that? And wouldn’t it be simpler to use non-integrating telomerase therapy to safely lengthen telomeres, like the approaches developed by Sierra Sciences and BioViva?

de Grey: We are making progress there, yes; in particular we have shown that telomerase-negative stem-cell reseeding works for the blood. However, no, the problem with non-integrating telomerase is that it will extend cancer telomeres just as much as normal cells’ telomeres. I support that research, though, not least because there may be breakthroughs in combating cancer in other ways (especially with the immune system), in which case it would be much safer to stimulate telomerase systemically.

Feinerman: Now we have very precise CRISPR, and removing genes is easier than inserting ones, because you can target the same cell more than once. When we solve the delivery problem, would we be able to apply WILT?

de Grey: Yes, certainly.

Feinerman: Why can’t we remove telomerase locally in compromised tissue?

de Grey: It’s being tried, but it is very difficult to make the removal selective.

Feinerman: There is growing evidence that epigenetic changes are highly organized and may be one of the causes of ageing. This allows some researchers to claim that ageing is a programme. It does not matter, however, how researchers see such changes — as a programme or as damage. By restoring the previous epigenetic profile by means of special reprogramming factors, we can turn an old cell into a young cell, and by resetting the profile, we can turn an adult cell into a pluripotent stem cell. Experiments show that restoring the epigenetic profiles of many cells in vivo rejuvenates an entire organism. What do you think? Maybe should we consider epigenetic changes as another type of damage in the SENS model, calling it EpiSENS?

de Grey: We need to be much more precise with definitions in order to answer your question. Epigenetic changes can be classified into two main classes: shift and noise. Shift means changes that occur in a coordinated manner among all cells of a given type and tissue, whereas noise means changes that occur in some such cells but not others, increasing the variability of that type of cell. Shifts are caused by some sort of program (genetic changes to the cell’s environment), so yes, they can potentially be reversed by restoring the environment and putting the program into reverse. Noise, on the other hand, is not reversible. And we have for several years worked on determining whether it happens enough to matter in a currently normal lifetime. We have not got to a definitive answer, but it’s looking as though no, epigenetic noise accumulates too slowly to matter, other than maybe for cancer (which, of course, we are addressing in other ways).

Feinerman: Should we use reprogramming factors to reverse the epigenetic programme?

de Grey: Probably not. There may be some benefits in doing so, as a way to restore the numbers of certain types of stem cells, but we can always do that by other methods (especially by direct stem cell transplantation), so I don’t think we will ever actually NEED to dedifferentiate cells in vivo.

Feinerman: One thing keeps me out of bed at night: the fear that stochastic nuclear DNA damage and mutations may play a big role in ageing. Ten years ago you proposed that most of the cells which have critical DNA mutations either undergo apoptosis, become senescent, or become cancerous. But if mutations are not critical, cells will live, accumulate them — one broken protein here, another one there — and it will finally lead to malfunction of the organ.

de Grey: Don’t worry. These mutations don’t accumulate nearly fast enough to harm us, because they are prevented by the same machinery that prevents cancer for a currently normal lifetime, and cancer can kill us as a result of only one cell doing the wrong thing, whereas non-critical mutations would need to affect a huge number of cells in order to affect the function of a tissue.

Feinerman: If it is proved that nuclear DNA damage and mutations play a role in ageing, do you have something in your pocket? I believe you already thought on that. How will we fix the problem? Maybe, extensive stem-cell therapy (like the proposed Whole-body Induced Cell Turnover)?

de Grey: Right. But they don’t play a role.

Note: Whole-body Induced Cell Turnover (WICT) consists of the qualitative and quantitative coordination of targeted cell ablation with exogenous cell administration so as to effect the replacement of a patient’s entire set of endogenous cells with exogenous cells (of the same quantity and cell type as the ablated endogenous cells they are replacing) derived from human pluripotent stem cells and directionally differentiated in vitro prior to their administration. The idea of WICT was firstly proposed in 2016 and improved in 2017.

The aim of WICT is the removal from the organismal environment of accumulated cellular and intracellular damage present in the patient’s endogenous cells, including telomere depletion, nuclear DNA damage and mutations, mitochondrial DNA damage and mutations, replicative senescence, functionally deleterious age-related changes in gene expression, and accumulated cellular and intracellular aggregates.

Feinerman: What do you think on the WICT? Combined with WILT, it looks like an all-in-one solution when implemented.

de Grey: The general idea of accelerating cell turnover is definitely a good one. It is a bit like the idea of replacing whole organs: if you replace the entire structure, you don’t need to repair the damage that the structure contains. However, also like replacement of organs, it has potential downsides, because evolution has give us a particular rate of turnover of particular cells, and the function of each of our cell types is optimised for that. So it may end up being complicated, with many pros and cons.

Feinerman: While other rejuvenating therapies (excepting, maybe, OncoSENS) are achievable in the near future and don’t involve special genetic surgery, full allotopic expression has a really long way to go. What do you think of the mimic approaches, for example, NMN, which raises the NAD+ level and restores mitochondrial function in a cell?

de Grey: It may help to preserve health a little, but I think it is very unlikely to extend life by more than a year or two on average (and it could be even less than that). But we are working hard to develop better methods of gene therapy that may make allotopic expression practical sooner than people think.

Feinerman: Oh, can you unveil the mystery?

de Grey: Well, basically we are combining two technologies that are both very very safe (in the sense that they have very low incidence of random DNA damage) but they have complementary limitations. One is CRISPR, which can make small changes very safely to a chosen location in the genome but cannot insert more than very small amounts of new DNA. The other is a very neglected system called BXB1, which can insert large amounts but only into a location that does not exist in the mammalian genome. Our idea is to use CRISPR to insert the BXB1 “landing pad” at a good location and then to use BXB1 to insert our chosen engineered genes at that location. We are developing this at the Buck Institute in Brian Kennedy’s lab.

Feinerman: Thank you for your explanation! However, there is a big problem with all genetic therapies. We need to target every cell in the body, and now it is nearly impossible. Our best delivery systems involving adeno-associated viruses (AAV) available today have only 10–50% efficiency. We should honestly admit that we still have no universal instrument for introducing new genes in an adult human. How will you solve this problem?

de Grey: We believe that the approach I described in my earlier answer will achieve a much higher efficiency, and because its lack of off-target effects, it means it can be used at much higher titer.

Feinerman: The main SENS approach is to rejuvenate our own bodies, but also there is a regenerative medicine which involves tissue and organ engineering. Won’t it be easier to print or grow new organs instead of rejuvenating the old ones? Of course, we cannot replace everything, but we can replace some critical parts: we can grow a new heart, liver, muscles, and, indeed, skin.

Note: Tissue and organ engineering is among the most fast-growing areas of regenerative medicine. Engineers have already bio-printed or grown in bioreactors almost all human organs. Now they are used mostly for testing new therapies or drugs. The main problem why they cannot be used for transplantation now is the vascularisation challenge. While engineers can bio-print or grow arteries and big vessels, they are still unable to create the vasculature — the web of tiny vessels and capillaries within the organ. Companies like Organovo pursue this goal and promise to solve it within next decade.

de Grey: That’s absolutely correct. I expect that in the early days of implementing SENS, some organs will be easier to replace than to repair. However, of course, replacing an organ requires invasive surgery, so we will want to develop repair eventually.

Feinerman: You emphasize that stem-cell research is already a well-advanced field, and SENS has not needed to get involved in this area. As far as I know, many stem-cell therapies are for very specific diseases and not for rejuvenation. Or will we get it as a side-effect?

de Grey: As you know, I don’t think that “diseases of old age” should be called diseases at all — they are parts of ageing, so their treatment is definitely part of rejuvenation. A great example right now is Parkinson’s disease — there are several stem-cell clinical trials in progress or in preparation for it.

Feinerman: Do you mean they are parts of ageing like a runny nose and cough are parts of flu? So treating them separately is as foolish as treating a cough without addressing the flu virus.

de Grey: It’s even worse than that. Treating runny nose and cough makes some sense, because the body will get on with attacking the flu virus anyway, and it makes sense to be less miserable during that time. But with ageing, we’re just talking about different parts of a phenomenon that the body does not know how to attack.

Feinerman: What in your opinion will be the order of arrival of rejuvenating therapies?

de Grey: Well, a lot of the stem-cell side of things is in clinical trials already, and removal of amyloid is there, too, in the case of Alzheimer’s. Next on the list will probably be senescent-cell ablation, which Unity are saying will be in the clinic next year, and removal of intracellular garbage for macular degeneration will also be, courtesy of our spinout Ichor. The other three are harder, but they are all chugging along!

Feinerman: There are about twenty various types of amyloids, we can see some success in removing transthyretin and beta-amyloid. What about others? Can we scale success in removing the above two on the others?

de Grey: I’m very confident that the removal of other amyloids can be achieved using more or less the same methods that have worked against those two. The next one on my list would be islet amyloid, which contributes to diabetes.

Feinerman: As far as I know intracellular junk in the eyes is not lipofuscin per se but A2E, oxidized form of vitamin A. Is there any progress in removing true lipofuscin — the more widespread form of intracellular junk?

de Grey: We have funded some preliminary work on that, but it’s still early. The difficulty is that lipofuscin is very heterogeneous, made up of many different components. Our strategy is to target it more like the way we target the extracellular matrix: rather than breaking it down, we want to identify some key crosslinks that are protecting it from being degraded by our existing lysosomal machinery.

Feinerman: Now everyone is obsessed with “ageing biomarkers” and the “biological clock”. Are they valid conceptions? Is it possible to have a single “clock” for the whole body? Maybe can we just use every type of damage as a biomarker and keep it below certain threshold?

de Grey: I agree with you — ultimately, we still need to fix the damage, so there is not much more that indirect proxy measures can tell us. These indirect measures are useful today, though, when we don’t have those repair therapies, because they help us to see what interventions may (slightly) slow down the accumulation of damage.

WHO, FDA, and New Medicine

Feinerman: FDA has a very long approval for new therapies or drugs. What do you think on medical tourism and biohacking as an alternative way?

de Grey: There have always been places with less restrictive regulatory systems for new drugs — medical tourism is nothing new. I think the key thing we should be doing more of is making better use of those who choose to go abroad to get treated: we should make it as easy as possible for them to report on what treatment they received and how well it worked, any side-effects, etc., for a long time after the treatment, so that such information can be analysed and used to guide future research. The people who provide experimental therapies don’t have any incentive to gather such data themselves, so it usually never gets gathered.

Feinerman: Do the SENS Research Foundation or any associated companies hold regular meetings with the FDA to inform them and clear the way for the new rejuvenation medicine? Some components of the SENS 1.0 panel are already in development or clinical trials, and others will arrive during next 20 years. These new coming medicines use completely different, repair-based rather than compensatory, approaches and need different clinical-trials protocol and a whole new health-care paradigm. The transition period has already begun, and we should use it wisely, otherwise the US may become an outsider in the medical world.

de Grey: I look forward to the day when we have such meetings, but that’s a little way off. That’s OK, though, because companies that are pursuing various components of SENS are indeed having such discussions. The FDA and its counterparts worldwide are being kept up to speed.

Feinerman: We already have many amazing results in the lab which can save human lives just now, but the lack of funding and the heavily regulated medical system don’t give them any chance to be in clinics in the coming years. With the current pace of progress, they will already be outdated before clinical trials. Do you think that translational research becomes the bottleneck?

Note: Even though 90% of US deaths and at least 80% of US medical costs are caused by ageing:

National Institutes of Health budget ($M): ~30,000
National Institute of Aging budget: ~1,000
Division of Aging Biology budget: ~150
Spent on translational research (max): ~10
SENS Research Foundation budget: ~5

These numbers speak for themselves; they are all you need to answer the question of when all of the discussed amazing therapies will be available in the clinics.

de Grey: I think things are improving. The idea of real rejuvenation is becoming more and more accepted. At this point, therefore, I would say that the main bottleneck is still at the earliest stage: the funding for work that is not yet investable.

Feinerman: The current WHO’s agenda is kind of a shame! They know that the fire is coming, but they prepare gasoline to put it out with. Do you agree that the conception of “healthy ageing” is a nonsense? Ageing cannot be healthy because if you are healthy you, well, do not age. The WHO forces people to be more comfortable with ageing instead of fighting with it. They recommend to spend billions to build more nursing houses and buy more wheelchairs instead of investing these money into rejuvenation biotechnology! It’s ridiculous!

de Grey: Well, I think we need to do both things: we need to maintain older people’s quality of life as best we can with the limited tools we have today, and we also need to develop better tools. Terms like “healthy ageing” are indeed double-edged: on the one hand there is, indeed, obviously no such thing, but on the other hand the terminology helps to emphasise that the purpose of all our work is to extend healthspan, with the extension of lifespan being simply a side-effect.

Rejuvenation Research Won’t Fund Itself

Feinerman: When I ask people to donate to SENS Research Foundation, they often say that their a few bucks don’t matter. Of course, they are wrong! Every dollar, even every cent matters! For example, how many people may read this? We assume 10,000. Well, if every of you will donate $50, only $50, per month, it will be over $5,000,000 per year! This sum will double current SENS budget. So, united we can change the world. We cannot and should not wait when governments and big pharma will fund rejuvenation research. (In fact they won’t; they will wait and see the first results.) We can do it ourselves! What can you say to our readers to encourage them?

de Grey: You are saying it really well. One way to say it is to calculate how many dollars it would take to save a life by donating to SENS. I estimate that a budget of $50 millions per year would let us go three times faster than now and would bring forward the defeat of ageing by about a decade. About 400 million people die of ageing in a decade, so that means donating to SENS has a bang-for-the-buck of roughly one life per dollar. No other cause comes anywhere near that.

Feinerman: Another doubt that people usually express is how does SENS Research Foundation do anything meaningful with such a small budget? While NIH and many others have hundreds of millions per year and cannot defeat ageing, SENS has only $5 millions per year. I answer that SENS is a highly efficient organization, goal-directed and result-oriented rather than process-oriented. Everyone can go through the SENS webpage and read last year’s annual report.

de Grey: Thank you! — that is indeed correct. Almost all research that is funded by governments is almost useless, because its effects on health will be tiny. SENS is different because it is a coherent, comprehensive plan for bring ageing under complete medical control.

Note: Unfortunately, I agree with Dr Aubrey de Grey. If you take a close look at NIH or NIA funded work… well… You will find hundreds of publications about obesity, lifestyle, air pollution, and their impact on longevity. Don’t you know that obesity, smoking, and much drinking of alcohol are bad for you? How can this information help us create a new cure against cancer, Alzheimer’s disease, or atherosclerosis? Do we really need another paper on it?

Also you can find many publications about calorie restriction and various genetic manipulations on worms and other model organisms that mimic it. Calorie restriction is everywhere! In the meantime, we have known for twenty years that CR does not work for humans. In 2015, $500,000 was given to projects like “A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline”. It’s not a joke, it’s a real research work! You can find more here. All that is useless because you cannot use it to produce working rejuvenation therapies. Only a small part of this work is useful in the sense of defeating ageing. Do you know what is the most interesting? It’s all your taxes, all your money! Now you know that.

At the same time really important research projects like work on glucosepane breaker therapy (which will end many ageing pathologies like arterial stiffness, chronic inflammation, hypertension, strokes, and will save many lives) in Spiegel Lab at Yale is permanently underfunded and would be closed last year without financial support from SENS Research Foundation and German entrepreneur Michael Greve. Finally, the cost of implementing the working rejuvenation treatments in old mice would by current estimates be only 1–2% of the Apollo Program. And the same amount of money and time was already spend on Sirtuins which have obviously produced nothing.

Feinerman: Can you say what Project|21 is, why it is so important and how people can help?

de Grey: Project|21 is our name for our appeal to wealthy individuals. We of course welcome donations of any size, but at present it remains the case that most of our income is donated by a small number of wealthy donors, so it stands to reason that we are doing all we can to attract more of those. What other people can do to help is easy — donate what you can, and encourage donations by friends who are wealthier than you!

Note: Project|21 is a new initiative created by SENS Research Foundation to end age-related disease through human clinical trials, starting in 2021, through investment in rejuvenation biotechnology.

Through three new programs, the Bridge fund, The Center of Excellence, and The Alliance Program, Project|21 will deliver the perfect environment for this fusion of opportunity and investment.

$50 million in total funding is required for Project|21, at least half of which will come from the members of SENS Research Foundation’s Group|21. Group|21 will bring together 21 philanthropists, each donating between $500,000 and $5 million. Grants, grassroots efforts, and matching-fund strategies will provide the remaining support. $5 millions was already donated by German Internet entrepreneur Michael Greve. Thank you, Mr. Greve! You are our hero!

Feinerman: Some people prefer to donate not to the whole organisation, but rather to concrete project or lab. Of course, it is not among the most convenient and efficient ways to manage money, but anyway do you consider such an option?

de Grey: Certainly yes. We sometimes have projects that cannot be funded because there is too little “unrestricted” money to go around, but for the most part we are able to make it work, so absolutely, if anyone wants to restrict a donation to a particular project, we are totally happy to work with that.

Feinerman: Now cryptocurrencies and blockchain technologies allow completely new and efficient ways for crowdfunding and investment. We can see as various no-name companies easily raise tens of millions dollars via ICOs for clearly doubtful projects. This occurs while really important areas like generative medicine, rejuvenation biotechnology, or bionics are permanently experiencing an acute thirst of money. Do you consider an ICO for Project|21? I believe it perfectly fits into ICO conditions and requirements!

de Grey: It’s definitely important for us, and we are working closely with various people who are experts in cryptocurrencies. Vitalik Buterin, who created Ethereum, is actually a donor. We very much hope to bring in substantial funding via that route.

Human Psychology, Not the Science, is the Key Issue in Defeating Ageing

Feinerman: When I ask people whether they want to live hundreds of years, many of them say, “No”, but when I ask them, whether they want to look and feel like 30, while being 70, they say, “Yes, of course!” I hope, you got my idea: people are afraid of big numbers. People don’t want to live forever; they just want not to be sick forever, even though big numbers logically emerge from not being sick. Have you ever regretted your claims about big numbers and 1000-year lifespans? People usually understand them in the wrong way. Some your colleagues say that without such claims, your ideas would be much more popular.

de Grey: It has always been a difficult decision. Yes, people are afraid of big numbers, and they are really bad at reasoning about the distant future. But the most important thing, in the long term, is that I am saying what I believe to be true and that I can always give very thorough, logical answers to any challenges. If I had gone out in 2005 saying that we could live to 150 with rejuvenation tech, and people had said why not 250, I would not have had a good answer, and people would not have trusted me. In the end it always works best if you tell the truth.

Feinerman: What do you think of 2013 work “The hallmarks of ageing”, which is obviously inspired by your seven types of damage? They look more sophisticated, and harder to deal with. Anyway, does it mean that researches finally demystified ageing and recognised it as a solvable problem?

de Grey: You’re right, it was definitely a reinvention of SENS. It had quite a few mistakes, but the basic idea of divide-and-conquer damage repair is identical. It is not at all more sophisticated; it’s the same. And yes, it means that mainstream researchers have finally accepted that ageing is now pretty well understood and is solvable.

Feinerman: Although biomedical gerontologists are not afraid to speak about ageing any more, as was the case 10 or even 5 years ago, which itself is a very big step, they are still very skeptical — at least publicly — about our ability to put ageing under medical control in the foreseeable future. You know many of them in person. Is it their real opinion? Maybe, face to face, they are more optimistic?

Note: I think that gerontologists should take a lesson from physicists and engineers. When physicists realised that our Sun uses a nuclear fusion reaction, they were excited by the idea to build a fusion reactor. Being full of courage, they started to work and immediately came across many obstacles. Although the reaction itself is very simple, the processes behind it are complex.

However, engineers haven’t given up or said: “We don’t fully understand these processes, so let’s stop working and study the Sun for 100 years.” They continued to work as hard as they could, built many working prototypes, and now we are much closer to commercial nuclear fusion reactor than ever before. And they are full of optimism! If you ask any physicist, whether it is possible to build such a reactor, the answer would be, “Yes, of course!” And if you ask an engineer, “When can we build it?”, he would probably say: “20–25 years, and it can be much sooner, if we have enough funding.” Sounds similar, doesn’t it?

Ageing is the same. But when you ask a gerontologist whether we can defeat ageing, he would likely call you a crazy. Why? They are both engineering problems!

de Grey: Well, maybe some of them are slightly more optimistic in private than they are in public, but really no — the problem is that they are basic scientists, so they are trained not to believe anything for which they do not have direct evidence. They just don’t like to speculate about time frames, even in private.

Feinerman: Yeah. With the current pace of progress, anything beyond 2030 is an uncertainty. However, what I know exactly is that if we want to have something working in 2030, we should work very hard in the right direction right now. So why do many [anti]ageing researchers consciously or unconsciously choose the most inefficient and ineffective way — altering metabolism via genetic manipulations or medications to only slightly possibly modestly slow down ageing — and use that as a proof (!) that we cannot radically extend human health and lifespan? Such an example is ridiculous by itself and nearly impossible in any research or engineering area, except biomedical gerontology!

de Grey: That is not something specific to anti-ageing research. In all research areas, the leaders always think they are right and take a long time to understand radically new ideas.

Feinerman: Maybe that is the reason? Maybe we need to have fewer gerontologists who merely study ageing and more biomedical engineers who repair damage? In other words we should switch our focus from ageing research to rejuvenation engineering. Since ageing is an engineering problem, then from the gerontologists’ point of view it looks like “not my job” to reverse it.

de Grey: Exactly. The main problem is that until “only” 17 years ago, no one had any coherent plan for fixing ageing, so it made sense to carry on treating gerontology as a basic science in which the priority was to discover more about it rather than to manipulate it. And 17 years is not very long in science, so the people who are most senior and influential are still the people who formed their mindset in the pre-rejuvenation era.

Feinerman: Unfortunately, the vast majority of biomedical engineers, those who do actual rejuvenation research, do not want to be associated with any [anti]ageing business and life extension, are not involved in longevity discussions, and usually keep silence. When pressed, they, however, are not very optimistic about life extension. It’s quite surprisingly to hear such claims from cutting-edge researchers, especially from those who recently promised to print or grow all vascularised human organs by 2035 and grow new limbs by 2030. If it is not about life extension, then what is it all about? Why do they behave in such a manner? Because of the pro-ageing trance? Or because they are too specialised and cannot see the whole picture?

For example, cell engineers make predictions as though there will be no progress in bionics, and bionics engineers make predictions as though there will be no progress in cell engineering. Each technology alone will not likely be te game changer, but when combined their impact will be enormous!

de Grey: You’ve got it. These technologies are developed largely independently of each other, so their leaders are largely unaware of how much progress is being made in the other areas. Since SENS is a divide-and-conquer approach, one cannot be optimistic about the overall outcome unless one is informed about all the components. That’s the main reason why I ran the Cambridge conference series starting in 2003, which is being revived in Berlin in March 2018 — to bring the leaders of these fields together.

Feinerman: Thank you very much for your amazing interview! Our conversation was wonderful! I wish you all your wishes come true as soon as possible. When we succeed, I hope we will shake our hands one hundreds years from now, walking along the waterfront of Mars City, which Elon Musk has promised to start to building in 2020s. Ah, and when you meet with him, remind him, please, that we will not be able to colonise Mars until we defeat ageing — because microgravity and cosmic radiation have the same implications on the human organism as premature ageing!

de Grey: Thank you for your support!

Afterwords

We live in the exciting era, The Era of Very Rapid Progress in science and technology — an era when many things which were merely science fiction only five years ago are common now, and things that are no more than science fiction now will be common in next five years. At the same time we live in The Era of Great Uncertainty — an era when our small everyday life decisions may have a huge impact on next several decades. One step to the right — and we may defeat ageing in twenty years. One step to the left — and the whole research areas will stagnate for another twenty years (as occurred in the case of glucosepane research).

New rejuvenation medicine is still very young and fragile, like the first spring flower after a dry and cold winter. In these days it especially needs our support! Even in such relatively advanced fields like stem cell or cancer research, there are gray, underfunded, and under-researched areas we need to care of.

Of course, you wish to know the time frames — when will we defeat ageing? You wish to know, will you personally benefit? Nobody knows. I intentionally did not ask Dr. Aubrey de Grey about the time frames and predictions. There will be no more time frames. Enough. Because they give you an illusion that some good clever guy will do all the work needed, while you may just relax, wait when he finishes, and “live long enough to live forever”. But he won’t! It is too big, too ambitious a project for one person. Now you know — your future is only in your hands. Not “live long enough…” but “work long enough…”! I always say that scientific and technological progress is a function of efforts — not of the time. The only way to get rid of a painful uncertainty and get to the definitive answer is to support meaningful rejuvenation research right now!

How can you help? Well, if you are a researcher yourself, then spend your time and money on the meaningful repair-based approach, which will produce working rejuvenation therapies in the foreseeable future. If you are a businessman — donate money to the SENS Research Foundation and its allies — Project|21, Methuselah Foundation, Forever Healthy Foundation, Life Extension Advocacy Foundation, or directly support research groups. Invest in the associated rejuvenation companies or found your own. If you are a celebrity, then use your fame to give attention to the problem and such research. If you are an ordinary person, well, you can encourage your more influential friends and do almost the same — just scale your abilities!

Some of you may ask: is it real? I hope we gave you enough evidence. Yes, of course, it’s real. Mover, it’s already happening! The right question, however, is whether it is happening fast enough to help us — currently living adult persons. And the answer is, probably, no. Of course, there may (and likely will) be many unexpected breakthroughs, but we should not rely on probability and scientific serendipity when we talk about human lives (especially our own). We should rely on a well-written plan, a reasonable budget and our efforts.

So the next question is, “Can we speed up the progress?” Yes, we can! All we need to do is what Dr. Aubrey de Grey said many times before and what I have just said above — unite against our main enemy and help researchers. But will we? Although people rarely think and behave rationally, I prefer to be cautiously optimistic! See you on Mars!

https://www.nextbigfuture.com/2017/12/wake-up-people-its-time-to-aim-high.html

Ariel VA Feinerman is a researcher, author, and photographer, who believes that people should not die from diseases and ageing, and whose main goal is to improve human health and achieve immortality.