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Is Reality Winner “One of Us”? – Article by William Sims Bainbridge

Is Reality Winner “One of Us”? – Article by William Sims Bainbridge

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The New Renaissance Hat
William Sims Bainbridge
July 26, 2017
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This article originally appeared on the website of the Institute for Ethics and Emerging Technologies (IEET) and is republished here with Dr. Bainbridge’s permission. 

Amidst the raging chaos in modern advanced nations, aggravated or rendered more visible by emerging technologies, an occasional individual person stands out, now notably Reality Winner.  Her Wikipedia page begins: “Reality Leigh Winner (born December 1991) is an American intelligence specialist employed by Pluribus International Corporation. Winner was arrested on June 3, 2017, on suspicion of leaking an intelligence report about Russian interference in the 2016 United States elections to the news website The Intercept. The report suggested that Russian hackers attacked a U.S. voting software supplier.”  Despite considerable journalistic attention, we cannot be sure we know exactly what Reality did, what its legal implications really are, and how her fate may be decided.  Yet today is not too early to consider the possible meaning of her remarkable story.

As soon as I learned about her arrest, I explored her Facebook page, and saw much that resonated with the humanistic values of future-oriented scholars and techno-visionaries, but soon that page vanished from public view.  Intense exploration of a host of online commentaries and information sources raised a profound general question illuminated by her specific case: Can futurists gently guide existing social institutions toward progress, within the context of conventional norms, or have we reached a grim point in history at which we must risk building a replacement for the civilization that is collapsing around us?

Reality Winner’s Facebook page was not awash in political radicalism, but presented a thoughtful person who was intensely dedicated to perfection of herself.  The five public Facebook groups to which she belonged were all real-world organizations promoting personal improvement in physical fitness.  CrossFitters of Augusta and CF 10-10 Members Group were local chapters of CrossFit, a network of organizations promoting a physical exercise philosophy advocating high-intensity training.  Another group was more specialized, GB Handstand Challenge, in which GB stands for Gymnastic Bodies.  The fourth of her public groups was vegetarian:  Vegan Recipes for Everyone.   During the brief time it was still visible, I checked Reality Winner’s Facebook page for “vegan” and saw that she used “#veganlifters” as a hashtag for an Instagram message she had posted at 6:10 AM on May 22, 2017: “Those days when you remind yourself the sacrifices you made to be here, now, every day.”  It struck me that her values seemed very similar to those of Transhumanism, seeking to attain human perfection, but through investment of personal effort and commitment to achieving difficult goals, rather than passively adopting some new technology.  Indeed, these four groups were technological, but advocating techniques that required well-disciplined human action, rather than taking some hypothetical nanotechnology vitamin pill.

The fifth group was a martial arts movement, Krav Maga Maryland, dedicated to “a military self-defense system developed for the Israel Defense Forces (IDF) and Israeli security forces (Shin Bet and Mossad).”  Wikipedia summarized the public information currently available about Reality Winner’s military career: “Winner served in the United States Air Force from 2010 to 2016, achieving the rank of senior airman with the 94th Intelligence Squadron.  She worked as a cryptologic linguist, and is fluent in Farsi, Dari and Pashto.  Winner was awarded the Air Force Commendation Medal.”  Farsi is the Persian language of Iran; Dari is a dialect of Farsi spoken in Afghanistan, and Pashto is the language of a major Afghan ethnicity.  Of course, we are not able to administer college advanced placement tests to Reality Winner, given her current incarceration, but she seems to invest the same energy and dedication into intellectual development, with respect to other cultures, as she does in physical fitness.

What about her humanity?  Many news websites copied the picture Reality Winner had posted on her Facebook on May 29, showing her overlooking Mayan ruins.  The day before, she had sent via Instagram another picture from the same archaeological site, with this comment: “Carved head at Lamanai, Belize, 100bc. This has been such a spiritual journey for me.”  We may all find spiritual significance in ancient ruins, but news reports mentioned that her father had died just a few months earlier, and she posted this touching paragraph on her Facebook page:  “There is nothing that can fix the hole in my heart that you left behind. I still don’t know who I am without you here or how to keep moving forward without the one person who believed unconditionally in everything I want to do in life. Old habits die hard, I still find myself making time to call you in the evenings or jotting down notes or stories to tell you next time we speak. Somehow, though, I feel like you are a little closer, here, among the pyramids you used to endlessly tell us about, and always hoped to see. It’s like I have a little piece of you here with me. I miss you, Dad. You would have loved to be here, though I’m sure you would have been bitching about the hot weather every minute.”

There is ample room to debate what punishment, if any, Reality Winner deserves for releasing classified US government information.  Many other people are currently leaking secret government information, and we may note that prominent people like former CIA director David Petraeus do not seem to suffer much when they commit similar acts.  There is some concern that Reality Winner will be given a harsh prison sentence, not because she deserves it, but to deter others from releasing damaging information, and to express the anger of the US President.  Her family seeks help in defending her through a Facebook group, named Friends of Reality Winner, and an online fundraiser at www.gofundme.com/2d9rnm64 that has not yet reached its modest goal to hire a good lawyer.

A number of political action groups briefly used her case in their campaign against the US President, and the document she made public is directly relevant to concerns about the election outcome.  However, it may be a mistake to blame one gang of politicians for our problems, investing false hopes in a competing gang who are not any better but employ different rhetoric and tactics.  Politicizing Reality Winner’s situation may only increase the harm she may suffer.  Following her family’s request to send her good wishes and contribute to her defense would seem to be the most immediately beneficial course, yet not satisfying our long-term ethical obligation.

Can current laws be changed to provide better protection for “whistleblowers” and others who provide information to journalists, scientists, and the general public that is needed for careful decision making?  Perhaps the secrecy laws should be changed so that they are strict only during the period of a formally declared war, which has not been the case for the US since 1945.  Whether from incompetence or corruption, both major US political parties fed false information to the public in escalation of the Vietnam War and the Second Iraq War.  It is hard to know the extent to which current public debates are poisoned by the desperation felt within the dying old-fashioned news media, as the information technology revolution erodes their influence and profits.  Yet there seems good reason to believe that the general public really should not trust the government that currently holds Reality Winner captive.  We are all journalists now, in the era of Facebook, Instagram, and the IEET website, so Freedom of the Press should be defined much more broadly, now that printing presses are obsolete.

This brings us to the most difficult pair of questions: How can we design a better civilization?  How could we bring that dream to reality?  Perhaps the answers cannot be based upon a hope that somehow progress in science and technology will automatically achieve such goals.  We may need to work exceedingly hard, as Reality Winner did in her self-improvement campaigns, transcending our human limitations through directed personal effort as much as through collective technical innovation.  We will need to reinvent modem culture, which requires honestly experimenting with many alternatives, not merely marching in lockstep to a single drummer.

Information technologies are having uncertain impacts on human societies, and the case of Reality Winner raises a host of related ethical issues, while calling into question our ability to extrapolate from the past, and asking for new policies.  Oh, those are the four principal questions raised by IEET!

Yes, Reality Winner is One of Us.

William Sims Bainbridge, Ph.D. is an IEET Senior fellow, and a prolific and influential sociologist of religion, science and popular culture. Dr. Bainbridge serves as co-director of Human-Centered Computing at the NSF.

AI and the Future of Free Markets: A Nuanced View – Preview of FreedomFest 2017 Panel Comments by G. Stolyarov II

AI and the Future of Free Markets: A Nuanced View – Preview of FreedomFest 2017 Panel Comments by G. Stolyarov II

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The New Renaissance Hat

G. Stolyarov II

July 18, 2017

Gennady Stolyarov II, Chairman of the United States Transhumanist Party, offers a preview of his forthcoming remarks at the July 21, 2017, FreedomFest panel in Las Vegas, entitled “Artificial Intelligence & Robots: Economy of the Future or End of Free Markets?”

Find more information regarding the FreedomFest panel here.

Visit the U.S. Transhumanist Party website here.

Become a member of the U.S. Transhumanist Party for free by filling out our concise application form.

U.S. Transhumanist Party Question-and-Answer Session – July 15, 2017

U.S. Transhumanist Party Question-and-Answer Session – July 15, 2017

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The New Renaissance Hat

G. Stolyarov II
B.J. Murphy
Bobby Ridge
Scott Jurgens
Martin van der Kroon

July 15, 2017

In this interactive question-and-answer session, scheduled for 11 a.m. U.S. Pacific Time on Saturday, July 15, 2017, U.S. Transhumanist Party Officers answered members’ and the public’s questions about the ongoing activities and objectives of the United States Transhumanist Party and also discussed other issues of interest that relate to emerging technologies and how to ensure the best possible future for sentient entities.

The following Officers were present for this Q&A session:

– Gennady Stolyarov II, Chairman
– B.J. Murphy, Director of Social Media
– Martin van der Kroon, Director of Recruitment
– Bobby Ridge, Secretary-Treasurer
– Scott Jurgens, Director of Applied Innovation

Because of an unexpected technical difficulty, the video stream was split into two portions.

Watch Part 1 here.

Watch Part 2 here.

Join the U.S. Transhumanist Party for free by filling out our membership application form at https://goo.gl/forms/IpUjooEZjnfOFUMi2.

Visit the U.S. Transhumanist Party website at http://transhumanist-party.org/.

Visit the U.S. Transhumanist Party Facebook page at https://www.facebook.com/USTranshumanistParty/.

Visit the U.S. Transhumanist Party Twitter page at https://twitter.com/USTranshumanist.

U.S. Transhumanist Party Interview with Kevin Baugh, President of Molossia

U.S. Transhumanist Party Interview with Kevin Baugh, President of Molossia

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The New Renaissance Hat
G. Stolyarov II
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To celebrate Founders’ Day – the 40th anniversary of the founding of the Republic of Molossia – representatives of the U.S. and Nevada Transhumanist Parties made an international trip on May 27, 2017, to join President Kevin Baugh in his micronation.

Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party, interviewed President Baugh on what attributes are needed to form a successful, long-lasting micronation, how micronationalism can inform our understanding of politics, countries, and governments, and how technology is essential to the development of micronations. Both micronationalism and technology have the potential to bring people closer together in terms of finding others who share similar interests and goals.

This speech by President Baugh provides background into the founding of Molossia and the concept behind it, as well as the ambitions for its future as a leading micronation of the world.

Find out about the Republic of Molossia here and read its Wikipedia entry here.

Visit the U.S. Transhumanist Party website here.

Become a member of the U.S. Transhumanist Party for free here.

Section XXII of the U.S. Transhumanist Party Platform reads: “The United States Transhumanist Party supports efforts at political, economic, and cultural experimentation in the form of seasteads and micronations. Specifically, the United States Transhumanist Party recognizes the existence and sovereignty of the Principality of Sealand, the Republic of Molossia, and the Free Republic of Liberland, and supports the recognition of these entities by all governments and political parties of the world.”

U.S. Transhumanist Party Interview with Travis McHenry, Grand Duke of Westarctica

U.S. Transhumanist Party Interview with Travis McHenry, Grand Duke of Westarctica

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The New Renaissance Hat
G. Stolyarov II
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Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party, interviews Grand Duke Travis McHenry of Westarctica on the attributes needed to form a long-lasting micronation, the role of technology in enabling more micronations to form over time, and what micronationalism can teach us about politics and organizational leadership.

Find out about Westartica here and read its Wikipedia entry here.

Visit the U.S. Transhumanist Party website here.

Become a member of the U.S. Transhumanist Party for free here.

Section XXII of the U.S. Transhumanist Party Platform reads: “The United States Transhumanist Party supports efforts at political, economic, and cultural experimentation in the form of seasteads and micronations. Specifically, the United States Transhumanist Party recognizes the existence and sovereignty of the Principality of Sealand, the Republic of Molossia, and the Free Republic of Liberland, and supports the recognition of these entities by all governments and political parties of the world.”

In the spirit of this plank, the U.S. Transhumanist Party also recognizes the nation of Westarctica and the efforts of Grand Duke Travis to eventually render its territory suitable for human habitation.

U.S. Transhumanist Party Discussion Panel on Life Extension – February 18, 2017

U.S. Transhumanist Party Discussion Panel on Life Extension – February 18, 2017

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The New Renaissance Hat

Listen to and download the audio recording of this panel discussion at http://rationalargumentator.com/USTP_Life_Extension_Panel.mp3 (right-click to download).

For its second expert panel, the U.S. Transhumanist Party invited Bill Andrews, Aubrey de Grey, Ira Pastor, and Ilia Stambler to discuss life extension and the quest to reverse biological aging through science and technology.

This two-hour panel discussion, moderated by Chairman Gennady Stolyarov II, took place on Saturday, February 18, 2017, at 10 a.m. U.S. Pacific Time. In this interactive venue, many opportunities for fresh discourse arose on the possibility of achieving dramatically greater longevity within our lifetimes. The substance of the discussion begins at 4:25 in the recording.

Questions the panelists considered include the following:

(i) How would you characterize the current state of efforts to reverse senescence / lengthen human lifespans?
(ii) How does progress in the areas of research you have delved into compare to your expectations approximately 10 to 15 years ago?
(iii) What are the most significant challenges and obstacles that you perceive to exist in the way of achieving serious reversal of biological aging?
(iv) What key technologies and methods of delivering treatments to patients would need to be developed in order for longevity escape velocity to be affordably achieved society-wide?
(v) What political reforms and societal / attitudinal changes would you advocate to accelerate the arrival of effective treatments to reverse biological aging and lengthen lifespans?
(vi) Are you concerned about any current political trends and how they might affect the progress of research into combating biological aging?
(vii) What can laypersons who are sympathetic to your goals do in order to hasten their realization? How can the effort to defeat aging become as popular and widely supported as efforts to defeat cancer and ALS are today?
(viii) What lessons can the history of anti-aging research offer to those who seek to advocate and help achieve effective scientific breakthroughs in this area in the coming years and decades?

Become a member of the U.S. Transhumanist Party for free. Apply here.

References

“Genetic stabilization of transthyretin, cerebrovascular disease, and life expectancy” – Paper by Louise S. Hornstrup, Ruth Frikke-Schmidt, Børge G. Nordestgaard and Anne Tybjærg-Hansen. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:1441-1447, Originally published May 15, 2013.

“Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy” – Paper by Ilia Stambler. Aging and Disease.

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Panelists

Dr. Bill Andrews is the President and CEO of Sierra Sciences – http://www.sierrasci.com/. As a scientist, athlete, and executive, he continually pushes the envelope and challenges convention. In his 35-year biotech career, he has focused the last 23 years on finding ways to extend the human lifespan and healthspan through telomere maintenance. As one of the principal discoverers of both the RNA and protein components of human telomerase, Dr. Andrews was awarded 2nd place as “National Inventor of the Year” in 1997.

Dr. Aubrey de Grey is the biomedical gerontologist who researched the idea for and founded SENS Research Foundation – http://www.sens.org/. 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.

Ira Pastor has 30 years of experience across multiple sectors of the pharmaceutical industry, including pharmaceutical commercialization, biotech drug development, managed care, distribution, OTC, and retail. He is the CEO of BioQuark, Inc. – http://www.bioquark.com/ – and Executive Chairman of ReAnima Advanced Biosciences – https://reanima.tech/.

Dr. Ilia Stambler is a researcher at Bar Ilan University, Israel. His research focuses on the historical and social implications of aging and life-extension research. He is the author of A History of Life-extensionism in the Twentieth Century – www.longevityhistory.com. He is actively involved in advocacy for aging and longevity research – www.longevityforall.org.

U.S. Transhumanist Party Discussion Panel on Aritificial Intelligence – January 8, 2017

U.S. Transhumanist Party Discussion Panel on Aritificial Intelligence – January 8, 2017

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The New Renaissance Hat

The U.S. Transhumanist Party’s first expert discussion panel, hosted in conjunction with the Nevada Transhumanist Party, asked panelists to consider emerging developments in artificial intelligence.

The panel took place on Sunday, January 8, 2017, at 10 a.m. U.S. Pacific Time.

This panel was moderated by Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party and Chief Executive of the Nevada Transhumanist Party. Key questions addressed include the following:

(i) What do you think will be realistic, practical applications of artificial intelligence toward improving human lives during the next 5 years?
(ii) Are you genuinely concerned about existential risk stemming from AI, or do you think those concerns are exaggerated / overhyped (or do you have some intermediate position on these issues)?
(iii) On the other hand, do you perceive significant tendencies in contemporary culture to overhype the positive / functional capabilities of AI?
(iv) How can individuals, particularly laypersons, become better at distinguishing between genuine scientific and technological advances in AI and hype / fear-mongering?
(v) What is your techno-optimistic vision for how AI can help improve the future of human (and transhuman) beings?
(vi) What are your thoughts regarding prognostications of an AI-caused technological Singularity? Are they realistic?

Panelists

Zak Field is an international speaker, consultant, games designer, and entrepreneur based in Norwich, UK. A rising thought leader in Mixed Realities (VR/AR), Zak speaks and consults on Mixed Realities-related topics like gamification, Virtual Reality (VR), Augmented Reality (AR), Robotics, Artificial Intelligences (AIs), and the Internet of Things (IoT).

In 2015, Zak partnered with Futurist Miss Metaverse as co-founder of BodAi, a robotics and AI company developing Bods, lifelike humanoid robot companions made accessible through a unique system that accommodates practical 21st-Century business and lifestyle needs.

David J. Kelley is the CTO for the tech venture capital firm Tracy Hall LLC, focused on companies that contribute to high-density sustainable community technologies, as well as the principal scientist with Artificial General Intelligence Inc. David also volunteers as the Chairman of the Transhuman National Committee board. David’s career has been built on technology trends and bleeding each research primarily around the capitalization of product engineering where those new products can be brought to market and made profitable. David’s work on Artificial Intelligence in particular – the ICOM research project with AGI Inc. – is focused on emotion-based systems that are designed to work around human constraints and help remove the ‘human’ element from the design of AI systems, including military applications for advanced self-aware cognitive systems that do not need human interaction.

Hiroyuki Toyama is a Japanese doctoral student at the Department of Psychology in University of Jyväskylä, Finland. His doctoral study has focused on emotional intelligence (EI) in the context of personality and health psychology. In particular, he has attempted to shed light on the way in which trait EI is related to subjective well-being and physiological health. He has a great interest in the future development of artificial EI on the basis of contemporary theory of EI.

Mark Waser is Chief Technology Officer of the Digital Wisdom Institute and D161T4L W15D0M Inc., organizations devoted to the ethical implementation of advanced technologies for the benefit of all. He has been publishing data science research since 1983 and developing commercial AI software since 1984, including an expert system shell and builder for Citicorp, a neural network to evaluate thallium cardiac images for Air Force pilots and, recently, mobile front-ends for cloud-based AI and data science. He is particularly interested in safe ethical architectures and motivational systems for intelligent machines (including humans). As an AI ethicist, he has presented at numerous conferences and published articles in international journals. His current projects can be found at the Digital Wisdom website – http://wisdom.digital/

Demian Zivkovic is CEO+Structure of Ascendance Biomedical, president of the Institute of Exponential Sciences, as well as a scholar of several scientific disciplines. He has been interested in science, particularly neuropsychology, astronomy, and biology from a very young age. His greatest passions are cognitive augmentation and life extension, two endeavors he remains deeply committed to, to this day. He is also very interested in applications of augmented reality and hyperreality, which he believes have incredible potential for improving our lives.

He is a strong believer in interdisciplinarity as a paradigm for understanding the world. His studies span artificial intelligence, innovation science, and business, which he has studied at the University of Utrecht. He also has a background in psychology, which he has previously studied at the Saxion University of Applied Sciences. Demian has co-founded Ascendance Biomedical, a Singapore-based company focused on cutting edge biomedical services. Demian believes that raising capital and investing in technology and education is the best route to facilitate societal change. As a staunch proponent of LGBT rights and postgenderism, Demian believes advanced technologies can eventually provide a definite solution for sex/gender-related issues in society.

A Transhumanist Opinion on Privacy – Article by Ryan Starr

A Transhumanist Opinion on Privacy – Article by Ryan Starr

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The New Renaissance HatRyan Starr

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Privacy is a favorite topic of mine. Maintaining individual privacy is a crucial element in free society. Yet there are many who want to invade it for personal or political gain. As our digital fingerprint becomes a part of our notion of self, how do we maintain our personal privacy on an inherently impersonal network of data? Where do we draw that line on what is private, and how do we enforce it? These are questions that are difficult to answer when looking at a short-term perspective. However, if we look further into the probable future, we can create a plan that helps protect the privacy of citizens today and for generations to come. By taking into account the almost certain physical merger of human biology and technology, the answer becomes clear. Our electronic data should be treated as part of our bodily autonomy.

The explosive success of social media has shown that we already view ourselves as partly digital entities. Where we go, what we eat, and who we are with is proudly displayed in cyberspace for eternity. But beyond that we store unique data about ourselves “securely” on the internet. Bank accounts, tax returns, even medical information are filed away on a server somewhere and specifically identified as us. It’s no longer solely what we chose to let people see. We are physical and digital beings, and it is time we view these two sides as one before we take the next step into enhanced humanity.

Subdermal storage of electronic data is here, and its storage capabilities will expand rapidly. Soon we will be able to store a lot more than just access codes for our doors. It is hard to speculate exactly what people will chose to keep stored this way, and there may even come a time when what we see and hear is automatically stored this way. But before we go too far into what will be stored, we must understand how this information is accessed in present time. These implants are currently based in NFC technology. Near-Field Communication is a method of storing and transmitting data wirelessly within a very short distance. Yes, “wireless” is the key word. It means that if I can connect my NFC tag to my smart phone by just waiving my hand close to it (usually within an inch or so), then technically someone else can, too. While current antenna limitations and the discreetness of where a person’s tag is implanted create a highly secure method of storage, advances in technology will eventually make it easier to access the individual. This is why it is urgent we develop a streamlined policy for privacy.

The current Transhumanist position is that personally collected intellectual property, whether stored digitally or organically, is the property of the individual. As such, it should be protected from unauthorized search and download. The current platform also states that each individual has the freedom to enhance their own body as they like so long as it doesn’t negatively impact others. However, it does not specify what qualifies as a negative impact or how to prevent it. Morphological freedom is a double-edged sword. A person can a person enhance their ability to access information on themselves, but they can also use it to access others. It is entirely feasible enhancements will be created that allow a person to hack another. And collecting personal data isn’t the only risk with that. What if the hacking victim has an artificial heart or an implanted insulin pump? The hacker could potentially access the code the medical device is operating with and change or delete it, ultimately leading to death. Another scenario might be hacking into someone’s enhanced sensory abilities. Much like in the novel Ender’s Game, a person can access another to see what they see. This ability can be abused countless ways ranging from government surveillance to sexual voyeurism. While this is still firmly within the realm of science fiction, a transhuman society will need to create laws to protect against these person-to-person invasions of privacy.

Now let’s consider mass data collection. Proximity beacons could easily and cheaply be scattered across stores and cities to function as passive collection points much like overhead cameras are today. Retail stands to gain significantly from this technology, especially if they are allowed access to intimate knowledge about customers. Government intelligence gathering also stands to benefit from this capability. Levels of adrenaline, dopamine, and oxytocin stored for personal health analysis could be taken and paired with location data to put together an invasive picture of how people are feeling in a certain situation. Far more can be learned and exploited when discreetly collected biodata is merged with publicly observable activity.

In my mind, these are concerns that should be addressed sooner than later. If we take the appropriate steps to preserve personal privacy in all domains, we can make a positive impact that will last into the 22nd century.
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Ryan Starr is the leader of the Transhumanist Party of Colorado. This article was originally published on his blog, and has been republished here with his permission.
Towards a Greater Knowledge of Mitochondrial DNA Damage in Aging – Article by Reason

Towards a Greater Knowledge of Mitochondrial DNA Damage in Aging – Article by Reason

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The New Renaissance HatReason
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Today I’ll point out a very readable scientific commentary on mutations in mitochondrial DNA (mtDNA) and the importance of understanding how these mutations spread within cells. This is a topic of some interest within the field of aging research, as mitochondrial damage and loss of function is very clearly important in the aging process. Mitochondria are, among many other things, the power plants of the cell. They are the evolved descendants of symbiotic bacteria, now fully integrated into our biology, and their primary function is to produce chemical energy store molecules, adenosine triphosphate (ATP), that are used to power cellular operations. Hundreds of mitochondria swarm in every cell, destroyed by quality control processes when damaged, and dividing to make up the numbers. They also tend to promiscuously swap component parts among one another, and sometimes fuse together.

Being the descendants of bacteria, mitochondria have their own DNA, distinct from the nuclear DNA that resides in the cell nucleus. This is a tiny remnant of the original, but a very important remnant, as it encodes a number of proteins that are necessary for the correct operation of the primary method of generating ATP. DNA in cells is constantly damaged by haphazard chemical reactions, and equally it is constantly repaired by a range of very efficient mechanisms. Unfortunately mitochondrial DNA isn’t as robustly defended as nuclear DNA. Equally unfortunately, some forms of mutation, such as deletions, seem able to rapidly spread throughout the mitochondrial population of a single cell, even as they make mitochondria malfunction. This means that over time a growing number of cells become overtaken by malfunctioning mitochondria and fall into a state of dysfunction in which they pollute surrounding tissues with reactive molecules. This can, for example, increase the level of oxidized lipids present in the bloodstream, which speeds up the development of atherosclerosis, a leading cause of death at the present time.

The question of how exactly some specific mutations overtake a mitochondrial population so rapidly is still an open one. There is no shortage of sensible theories, for example that it allows mitochondria to replicate more rapidly, or gives them some greater resistance to the processes of quality control that normally cull older, damaged mitochondria. The definitive proof for any one theory has yet to be established, however. In one sense it doesn’t actually matter all that much: there are ways to address this problem through medical technology that don’t require any understanding of how the damage spreads. The SENS Research Foundation, for example, advocates the path of copying mitochondrial genes into the cell nucleus, a gene therapy known as allotopic expression. For so long as the backup genes are generating proteins, and those proteins make it back to the mitochondria, the state of the DNA inside mitochondria doesn’t matter all that much. Everything should still work, and the present contribution of mitochondrial DNA damage to aging and age-related disease would be eliminated. At the present time there are thirteen genes to copy, a couple of which are in commercial development for therapies unrelated to aging, another couple were just this year demonstrated in the lab, and the rest are yet to be done.

Still, the commentary linked below is most interesting if you’d like to know more about the questions surrounding the issue of mitochondrial DNA damage and how it spreads. This is, as noted, a core issue in the aging process. The authors report on recent research on deletion mutations that might sway the debate on how these mutations overtake mitochondrial populations so effectively.

Expanding Our Understanding of mtDNA Deletions

A challenge of mtDNA genetics is the multi-copy nature of the mitochondrial genome in individual cells, such that both normal and mutant mtDNA molecules, including selfish genomes with no advantage for cellular fitness, coexist in a state known as “heteroplasmy.” mtDNA deletions are functionally recessive; high levels of heteroplasmy (more than 60%) are required before a biochemical phenotype appears. In human tissues, we also see a mosaic of cells with respiratory chain deficiency related to different levels of mtDNA deletion. Interestingly, cells with high levels of mtDNA deletions in muscle biopsies show evidence of mitochondrial proliferation, a compensatory mechanism likely triggered by mitochondrial dysfunction. In such circumstances, deleted mtDNA molecules in a given cell will have originated clonally from a single mutant genome. This process is therefore termed “clonal expansion.”

The accumulation of high levels of mtDNA deletions is challenging to explain, especially given that mitophagy should provide quality control to eliminate dysfunctional mitochondria. Studies in human tissues do not allow experimental manipulation, but large-scale mtDNA deletion models in C. elegans have proved to be helpful, showing some conserved characteristics that match the situation in humans, as well as some divergences. Researchers have used a C. elegans strain with a heteroplasmic mtDNA deletion to demonstrate the importance of the mitochondrial unfolded protein response (UPRmt) in allowing clonal expansion of mutant mtDNAs to high heteroplasmy levels. They demonstrate that wild-type mtDNA copy number is tightly regulated, and that the mutant mtDNA molecules hijack endogenous pathways to drive their own replication.

The data suggests that the expansion of mtDNA deletions involves nuclear signaling to upregulate the UPRmt and increase total mtDNA copy number. The nature of the mito-nuclear signal in this C. elegans model may have been the transcription factor ATFS-1 (activating transcription factor associated with stress-1), which fails to be imported by depolarized mitochondria, mediates UPRmt activation by mtDNA deletions. A long-standing hypothesis proposes that deleted mtDNA molecules clonally expand because they replicate more rapidly due to their smaller size. To address this question, researchers examined the behavior of a second, much smaller mtDNA deletion molecule. They found no evidence for a replicative advantage of the smaller genome, and clonal expansion to similar levels as the larger deletion. In human skeletal muscle, mtDNA deletions of different sizes also undergo clonal expansion to the same degree. Furthermore, point mutations that do not change the size of the total mtDNA molecule also successfully expand to deleterious levels, indicating that clonal expansion is not driven by genome size. Thus, similar mechanisms may be operating across organisms. In the worm, this involves mito-nuclear signaling and activation of the UPRmt.

There is some debate over interpretation of results. One paper indicates that UPRmt allows the mutant mtDNA molecules to accumulate by reducing mitophagy. Another demonstrates that the UPRmt induces mitochondrial biogenesis and promotes organelle dynamics (fission and fusion). Both papers show that by downregulating the UPRmt response, mtDNA deletion levels fall, which may allow a therapeutic approach in humans. Could there be a similar mechanism in humans, especially since some features detected in C. elegans are also present in human tissues, including the increase in mitochondrial biogenesis and the lack of relationship between mitochondrial genome size and expansion? It is likely that there will be a similar mechanism to preserve deletions since, as in the worm, deletions persist and accumulate in human tissues, despite an active autophagic quality-control process. Although the UPRmt has not been characterized in humans as it has in the worm, and no equivalent protein to ATFS-1 has been identified in mammals, proteins such as CHOP, HSP-60, ClpP, and mtHSP70 appear to serve similar functions in mammals as those in C. elegans and suggest that a similar mechanism may be present.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.
Crowdfunding Longevity Science: An Interview with Keith Comito of Lifespan.io – Article by Reason

Crowdfunding Longevity Science: An Interview with Keith Comito of Lifespan.io – Article by Reason

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Keith Comito leads the volunteers of the non-profit Life Extension Advocacy Foundation (LEAF) and the crowdfunding initiative Lifespan.io, a site I’m sure you’ve seen at least in passing by now. The LEAF crew have put in a lot of effort to help make fundraisers for rejuvenation research projects a success both last year and this year. Two such crowdfunding campaigns are running right now, firstly senolytic drug research at the Major Mouse Testing Program with just a few days left to go, and in its stretch goals, and secondly the recently launched drug discovery for ALT cancers at the SENS Research Foundation. Both tie in to the SENS portfolio of research programs aimed at effective treatment of aging and all age-related conditions. These are large projects when taken as a whole, but the way forward in this as in all things is to pick out smaller, achievable goals, and set out to get them done. Then repeat as necessary.

I recently had the chance to ask Keith Comito a few questions about Lifespan.io, the state of funding for the interesting end of longevity science, and what he envisages for the years ahead. This is an interesting, revolutionary time for the life sciences, in which progress in biotechnology has made early stage research very cheap. A great deal can be accomplished at the cutting edge of medical science given access to an established lab, administrators who can break out small initiatives from the larger goals, smart young researchers, and a few tens of thousands of dollars. It is an age in which we can all help to advance the research we care about, by collaborating and donating, and it has never been easier to just reach out and talk to the scientists involved. If you haven’t taken a look at Lifespan.io and donated to one of the projects there, then you really should. This is a way to move the needle on aging research, and advance that much closer to effective treatments for the causes of aging.

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What is the Lifespan.io story in brief? What was the spur that made you come together and decide to do your part in the fight against aging?

Lifespan.io began to take shape at the tail end of 2012, as a result of a loose discussion group based in New York which consisted of citizen scientists such as myself and Dr. Oliver Medvedik, supporters of SENS, as well as a few healthcare practitioners. We began having monthly meetings to discuss what could be done to accelerate longevity research (usually in oddball locations like salad bars or subterranean Japanese restaurants befitting our motley crew) and eventually hit upon the idea of crowdfunding. What drew us to this idea was that it was something tangible: a concrete way to move the needle on important research not only through funds, but through raised awareness. It is fine to talk and rabble-rouse about longevity, but we felt such efforts would be much more effective if they were paired with a clear and consistent call to action – a path to walk the walk, so to speak. As this idea coalesced we formed the nonprofit LEAF to support this initiative, and the rest is history. Not every one from the initial discussions in 2012 remained throughout the intervening years, but we are thankful to all who gave us ideas in those early days of the movement.

I’d like to hear your take on why we have to advocate and raise funds at all – why the whole world isn’t rising up in support of treatments for the causes of aging.

The reasons why people and society at large have not prioritized anti-aging research thus far are myriad: fear of radical change, a history of failed attempts making it seem like a fools errand, long timescales making it a difficult issue for election-focused politicians to support, etc. The reason I find most personally interesting relates to cognitive bias – specifically the fact that our built-in mental hardware is ill-equipped to handle questions like “do you want to live 100 more years?” If instead you ask the questions “Do you want to be alive tomorrow?” and “Given that your health and that of your loved ones remains the same, do you suspect your answer to the first question will change tomorrow?”, the answers tend to be more positive.

This leads me to conclude that the state of affairs is not necessarily as depressing for our cause as it might appear, and that reframing the issue of healthy life extension in a way that will inspire and unite the broader populace is possible. Aubrey de Grey has spoken about “Longevity Escape Velocity” in relation to the bootstrapping of biomedical research, but I think the same idea applies to the public perception of life extension as well. The sooner we can galvanize the public to support therapies that yield positive results the easier it will become to invite others to join in this great work. It is all about jump starting the positive feedback loop, and that is why we believe rallying the crowd behind critical research and trumpeting these successes publicly is so vitally important.

What the future plans for Lifespan.io and the Life Extension Advocacy Foundation?

In addition to scaling up our ability to run successful campaigns on Lifespan.io, we look forward to improving our infrastructure at LEAF by bringing on some staff members to join the team. LEAF has largely been a volunteer effort thus far, and having the support of a staff will allow us to take on more campaigns as well as further improve the workflow to create and promote them. This will also free me up personally to more actively pursue potential grand slams for the movement, such as collaborations with prominent YouTube science channels to engage the public and policy related goals like the inclusion of a more useful classification of aging in the ICD-11.

Do you have any favored areas in research at the moment? Is there any particular field for which you’d like to see researchers approaching you for collaboration?

Senolytics is certainly an exciting area of research right now (congratulations Major Mouse Testing Program!), and a combination of successful senolytics with stem cell therapies could be a potential game changer. That being said I’d also like to see projects which address the truly core mechanics of aging, such as how damage is aggregated during stem cell division, and the potential differences in this process between somatic and germ cells. How can the germ line renew itself for essentially infinity? The real mystery here is not that we grow old, but how we are born young.

A related question: where do you see aging and longevity research going over the next few years?

In the near future we will likely continue to see the pursuit of compounds which restore bodily systems failing with age to a more youthful state. This will include validating in higher organisms molecules that have shown this sort of promise: rapamycin, metformin, IL-33 for Alzheimer’s, etc. This approach may sound incremental, but it actually signals a great paradigm shift from the old system of mostly ineffective “preventative measures” such as antioxidants. Things like nicotinamide mononucleotide (NMN), IL-33 – if successful these types of therapies can be applied when you are old, and help restore your bodily systems to youthful levels. That would be a pretty big deal.

Funding is ever the battle in the sciences, and especially for aging. Obviously you have strong opinions on this topic. How can we change this situation for the better?

I believe the key to greater funding, both from public and private sources, is to build up an authentic and powerful grassroots movement in support of healthy life extension. Not only can such a movement raise funds directly, but it also communicates to businesses and governments that this is an issue worth supporting. An instructive example to look at here is the work of Mary Lasker and Sydney Farber to bring about the “War on Cancer”. Through galvanizing the public with efforts such as the “Jimmy Fund”, they effected social and political change on the issue, and helped turn cancer from a pariah disease into a national priority. If we all work together to build an inclusive and action-orientated movement, we can do the same.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.