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The Rise of Oisin Biotechnologies – Interview with Gary Hudson, CEO of Oisin Biotechnologies, by Ariel VA Feinerman

The Rise of Oisin Biotechnologies – Interview with Gary Hudson, CEO of Oisin Biotechnologies, by Ariel VA Feinerman

Ariel VA Feinerman
Gary Hudson


Gary Hudson

Preface

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 cause 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! 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 rainy Seattle, we meet Gary Hudson!

He has been involved in private space flight development for over 40 years. Hudson is best known as the founder of Rotary Rocket Company, which in spending ~$30 Million attempted to build a unique single stage to orbit launch vehicle known as the Roton. He helped found Transformational Space T/Space in 2004 and AirLaunch LLC which was awarded the DARPA/USAF FALCON project in 2003.

Previous projects included designs of the Phoenix SSTO, the Percheron, and other rockets, founder of Pacific American Launch Systems, and various consulting projects. Currently, he is the President and CEO of the Space Studies Institute.

Now Hudson brings his excellent engineering skills into rejuvenation biotechnology! He is a founding partner of Oisin Biotechnologies, who are developing a liposomally delivered DNA therapy for the removal of senescent cells from the body. Hudson provided an initial seed donation to help fund the creation of the Methuselah Foundation and SENS Research Foundation.

Interview

Feinerman: Hello, Mr Gary Hudson!

Hudson: Thanks for inviting us to this interview!

Feinerman: You have recently visited an amazing Undoing Aging 2018 conference, which took place in Berlin, 15–17 March, where your colleague, Matthew Scholz, was a speaker. What is your impression?

Hudson: It was a great conference with several important presentations. It put me in mind of the early SENS conferences in Cambridge, UK, which I helped to sponsor. I understand it will now become an annual event. Our CSO Dr. John Lewis also gave an important summary of our work to date.

Feinerman: Will Oisin’s presentations from conference be available for general public?

Hudson: I believe that the SENS Foundation will be posting them but I don’t have details about the timing.

FeinermanYour last interview was in July 2017, more than half a year ago. What has been accomplished?

Hudson: We have conducted many pre-clinical mouse experiments on both cancer and senescent cell removal. All have been successful and produce very remarkable results. We’ve also conducted a pilot toxicity and safety trial on non-human primates. The results of that trial were also successful and encourage us to proceed to human safety trials as soon as regulatory authorities approve them. We have also spun-out a cancer-focused company, Oisin Oncology, and raised a seed round for that venture.

Feinerman: Great to hear! However, when can we see some papers? People usually trust papers more than mere interviews or press releases. Of course, papers need many efforts not related to research but they will allow you attract more attention from general public, researchers, and investors.

Hudson: Papers are being prepared now for submission to major journals, but that process takes time, especially the peer review. For the moment, most of our data is only available to investors and partners in pharma and the biotech industry.

Feinerman: You planned human clinical trials, have you carried them out?

Hudson: It takes quite some time to organize a human trial and to get it approved. Before one can be conducted, we have to set up so-called “GMP (Good Manufacturing Practice) manufacture of our therapeutic, and then we have to conduct “GLP (Good Laboratory Practice) Tox” studies in two different species. Once that is all completed later this year, then we can begin a human safety trial, or a “Phase 1” trial. All this takes time, but we hope that first safety trials in oncology indications might begin this year, or in early 2019.

Feinerman: Does that mean we have a race between Unity Biotechnology and Oisin and you have all chances to win the race?

Hudson: I don’t see it as a race or a competition. I believe that future anti-aging treatment will require multiple complimentary approaches.

Feinerman: When we can expect your therapy available in the clinic?

Hudson: It’s very difficult to predict. I believe that our cancer treatment will make it to the clinic first, and that could happen in less than five years. Since the FDA doesn’t regard ageing as an indication, it may take longer for our SENSOlytic™ treatment to reach the public, since the regulatory environment will need to change.

Feinerman: As Michael Rae has said, we need not to wait when ageing will be recognised as a disease. You can mark your senolytics as a therapy for specific ageing pathology like fibrosis or chronic inflammation in the same way as Unity does.

Hudson: This is certainly true and is part of our strategy, but many of those endpoints are more difficult to ascertain than oncology endpoints. Additionally, going after oncology approvals can be faster and easier to get to clinic. But we will push forward on several fronts as funding permits.

Feinerman: In your previous interview you have said that you make some tweaks to both the promoter side and the effector side of the constructs that will provide even more interesting and useful extensions to the basic capability, but you can’t discuss those for IP reasons. Can you now say about them?

Hudson: I still can’t say too much about them, but we have conducted animal trials on some of these “tweaks” and they work quite well. The downside to the matter is that every “tweak” requires new trials, and our goal is to get something to the clinic as soon as possible, so many of the improvements will have to wait. Progress is limited based on available funds and personnel resources, of course, but we will move as quickly as we can.

Feinerman: Do you use any CAD software to design your constructs? Are you going to make them public so independent engineers will be able to help you identify new useful pairs of promoters and effectors? Your technology is so powerful that Open Source approach would be very helpful!

Hudson: No, the design of the current constructs are very straightforward and simple. As our patents are issued, their design will become public. If people wish to design their own constructs for particular applications they may contact us for collaboration, though we do have several collaborations active at the moment so we may already be working on similar ideas.

Feinerman: What do you think on targeting your machinery on cells with abnormal telomerase activity to kill cancer? Can you use several conditions — like in programming — several promoters to be more specific?

Hudson: If we targeted telomerase we’d also kill stem cells, just like the side effects of much of conventional chemotherapy. That’s probably not a good idea. But multiple promoters, or synthetic promoters, might be used to achieve the aims of killing only cancer cells. Our initial therapeutic will likely just employ p53 promoter targeting, since we have good data that works.

Feinerman: Yeah, the same issue as when we remove or break telomerase gene: there would be nice to do this only in compromised tissue, but as researchers say it is very difficult to make the removal selective. However, it is not a problem with ALT genes, which cause 15–20% of cancers. Are you going to collaborate with the OncoSENS lab? Also killing cells actively expressing telomerase will be very useful in WILT implementation.

Hudson: We’ve had conversations with the SENS Foundation about OncoSENS and cooperated in a preliminary fashion, but I don’t believe it is currently a research priority for them. We already have enough projects to keep us busy for some time, too!

Feinerman: Now you use only suicide gene as an effector, do you plan to use other genes? For example to enhance the cells, give them ability to produce new enzymes, or temporarily shut down telomerase to help anti-cancer therapy to be more effective.

Hudson: We believe we can express any gene under the control of any promoter we wish to use, so the possibilities are almost endless.

Feinerman: Now we know that epigenetic changes (shift) play a huge role in ageing. Even though there is no consensus among researchers whether they are a cause or a consequence of ageing, experiments show that temporal expression of OSKM transcription factors may have some health benefits by restoring “young” epigenetic profiles. You can remember the Belmonte work, for example. However, the problem in their work is that they used transgenic mice and express OSKM in every their cell. If you temporarily express OSKM in an “old” cell, that is OK, you can “rejuvenate” such a cell. While if you express OSKM in a stem cell which is already biologically “young”, you can force the cell into iPSC, which is a way to cancer. Using your machinery we can target only cells which have “old” expression profiles, and involving normal mice! Such a work will be much “cleaner” and safer than Belmonte’s work.

Hudson: With respect to your comments about reprogramming, Oisin is currently working with a university group on exactly this approach, but I can’t say more at this time. We also believe that first you have to clear existing senescent cells, then you can reprogram successfully.

Feinerman: How many resources, finances, and personnel do you need to move as quickly as possible? Do you have open positions? Maybe, some of our readers have enough finances or experience.

Hudson: We could effectively spend tens of millions or dollar or more, very easily, but it isn’t realistic to assume we could raise that amount — and if we did, we’d lose control of Oisin’s ageing focus, since investors would most likely want us to aim at quick returns. We are always interested in talking with “mission minded” investors, however. As for hiring, we have to do that slowly and judiciously, since labour is one of the biggest costs to a start-up company, and over-hiring can sink a project quickly. We already have more potential hires than we can bring on-board.

Feinerman: Now cryptocurrencies and blockchain technologies allow completely new and efficient ways for investments. We can see this as various no-name companies easily rise tens of millions dollars via ICOs for clearly doubtful projects. Would you like to make an ICO? Oisin shows real progress and can easily rise big sums! People say that they will be glad to buy your tokens if you issue them. You have said that you prefer to work with “mission minded” investors. There are thousands people out there who can invest from $1,000 to $100,000 in cryptocurrencies and who believe that radical extension of healthy life is possible!

If you are worried about legal issues, you can use various cryptocurrency investment funds who act like proxies between holders of cryptocurrencies and companies.

Hudson: We have investigated several of these financing options, but we are not expert in this area, so we have been reluctant to move too quickly. But we continue to have conversations with relevant parties. There is a lot of regulatory uncertainty surrounding ICOs, however, so we must move cautiously.

Feinerman: Now we know enough about ageing to defeat our main enemy. Do you agree that first comprehensive rejuvenation panel is not a scientific problem and even not an engineering problem, but a problem of engineering management?

Hudson: I wouldn’t say that there is no science left to do, but as an engineer myself I naturally agree that proper engineering management and program management skills must be brought to bear on the problem of ageing.

Feinerman: One person has said, we get what we ask for. Can we now aim high and publicly claim that our main goal is not additional five years of life but LEV — Longevity Escape Velocity and finally unlimited healthy life?

Hudson: This is a difficult “public relations” problem. Most investors, the scientific community, and the public are not yet ready to embrace the notion of longevity escape velocity. Thus at Oisin we do pitch health span as a primary goal. But personally I don’t believe that you can obtain health span improvements without making significant progress towards LEV. So in the end, I think we get LEV by targeting health span, and we reduce the controversy by doing so.

Feinerman: Some people ask me how to buy your stocks or invest in Oisin. What can you say?

Hudson: We do have a number of private investors (angel investors) who are “mission minded” or “mission focused” and we welcome discussions with qualified investors and firms who share our vision for dealing with ageing and cancer. Accredited investor candidates may contact us at info@oisinbio.com

Feinerman: David Gobel claims that “By advancing tissue engineering and regenerative medicine, we want to create a world where 90-year olds can be as healthy as 50-year olds by 2030.” And I secretly hope that 40 will become new 30 or even 20 by 2030! Can we achieve that — in principle?

Hudson: I certainly hope so! In 2030 I’ll be 80, so I’m looking forward to feeling like I’m 40…

Feinerman: Thank you very much for your amazing answers! That was a real pleasure to talk with such a great man like you. I hope we all will succeed in our goal and will have hundreds, thousands, and — who knows? — maybe even millions years of healthy life!

Hudson: It is kind of you to say so, but I only consider myself fortunate to be working with the really great men and women in the anti-aging community who are doing the real work. I’m only trying to facilitate their efforts and get treatments to the clinic as fast as possible. I don’t know what will be possible in the long term, but anything will be better than letting nature run its course, producing sickness and declining functional health.

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.

Message from Ariel VA Feinerman: If you like my work, any help will be appreciated!

PayPal: arielfeinerman@gmail.com

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Beginners’ Explanation of Transhumanism – Bobby Ridge and Gennady Stolyarov II

Beginners’ Explanation of Transhumanism – Bobby Ridge and Gennady Stolyarov II

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Bobby Ridge
Gennady Stolyarov II


Bobby Ridge, Secretary-Treasurer of the U.S. Transhumanist Party, and Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party, provide a broad “big-picture” overview of transhumanism and major ongoing and future developments in emerging technologies that present the potential to revolutionize the human condition and resolve the age-old perils and limitations that have plagued humankind.

This is a beginners’ overview of transhumanism – which means that it is for everyone, including those who are new to transhumanism and the life-extension movement, as well as those who have been involved in it for many years – since, when it comes to dramatically expanding human longevity and potential, we are all beginners at the beginning of what could be our species’ next great era.

Become a member of the U.S. Transhumanist Party for free, no matter where you reside.

See Mr. Stolyarov’s presentation, “The U.S. Transhumanist Party: Pursuing a Peaceful Political Revolution for Longevity“.

In the background of some of the video segments is a painting now owned by Mr. Stolyarov, from “The Singularity is Here” series by artist Leah Montalto.

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.

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.

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

Steve Hill

Dr. Aubrey de Grey


Editor’s Note: In this article, Steve Hill highlights the Ask Me Anything on Reddit held on December 7th by Dr. Aubrey de Grey.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 13, 2017

 

Dr. Aubrey de Grey from the SENS Research Foundation (SRF) did an Ask Me Anything on Reddit on December 7th, and there were many great questions and answers; we thought it would be a great time to summarize some of the best ones and offer a little commentary.

What do you think were the biggest wins of the last couple of years in SENS-relevant advocacy, research, and development? What has moved the needle?

There have been lots. On the research, I would highlight our paper in Science two years ago, which shows how to synthesize glucosepane, and our paper in Nucleic Acids Research one year ago, which shows simultaneous allotopic expression of two of the 13 mitochondrial genes. Both of those projects have been greatly accelerated in the meantime as a result of those key enabling breakthroughs; watch this space.

On advocacy, I think the main win has been the arrival of private capital; I would especially highlight Jim Mellon and his Juvenescence initiative because he is not only a successful, energetic and visionary investor, he is also a highly vocal giver of investment advice.

We are pleased to have been involved with the second project mentioned here, as we hosted the MitoSENS project at Lifespan.io, where it raised 153% of its initial fundraising goal. Less than a year later, after raising this money, it went on to publish the groundbreaking study showing that backup copies of mitochondrial genes could indeed be created in the nucleus. Dr. de Grey originally proposed the idea over a decade ago amid much scepticism; it is really good to see that years later he has been vindicated. This is the power of crowdfunding and how we as a community can make big changes in science by working together.

How do you feel about the impact of groups like LEAF advocating and reporting on rejuvenation biotech? Has the advocacy and reporting of these groups made your life any easier?

Massively! A huge thing that I say all the time is that advocacy absolutely relies upon the diversity of its messengers. Different people listen to different forms of words, different styles of messaging, etc. The more, the better.

It’s good to know that our work is appreciated and helping. Working together as a community is essential for progress, so it was nice to see this question and response from someone we respect a great deal.

We have said many times before effective advocacy efforts are just as important as the research itself. Professional advocacy has the potential to increase public support and funding, paving the way for the arrival of rejuvenation biotechnology. In the past decade or so, advocacy has mostly been left to volunteers and people such as Dr. de Grey.

Popular causes attract celebrities, public support, funding and investment; if we want a revolution in medicine and how we treat aging, then we must popularize the movement. There has been a serious shortage of full-time and organized advocacy; therefore, we decided to create LEAF to support groups like the SRF, advocate to popularize the cause, and help to raise much-needed funds for research efforts. We are only able to do this thanks to the support of the community, and we are extremely grateful to our Lifespan Heroes for helping us to do the work we do.

Aside from funding, what do you consider to be a burden or delay for your type of research?

Nothing. Seriously, nothing at all. We have the plan, and we have the people. It’s all about enabling those people by giving them the resources to get on with the job.

Indeed, funding for research is one of the four major bottlenecks slowing down the development of therapies that address the aging processes. The more funding the field gets, the more projects can be launched, the sooner breakthroughs can potentially happen, and the greater the benefits will likely be for all of us.

Is there anything new you are able to say about the breaking of cross-links in the extracellular matrix?

Absolutely. Short story, we now have a bunch of glucosepane-breaking enzymes, and we are within a few months of spinning the work out into a startup.

A suspected cause of degenerative aging is the accumulation of sugary metabolic wastes known as advanced glycation end-products (AGEs). These are wastes that are, in some cases, hard for our metabolism to break down fast enough or even at all. Some types, such as glucosepane, can form cross-links, gumming together important proteins such as those making up the supporting extracellular matrix scaffold.

The properties of elastic tissues (skin and the blood vessel walls) derive from the particular structure of the extracellular matrix, and cross-links degrade that structure, preventing it from functioning correctly. AGEs’ presence contributes to blood vessel stiffening with age, and it is implicated in hypertension and diabetes.

That SRF now has candidate enzymes is very significant because it means that there are now potential ways to remove these crosslinks from our tissues. There are many types of crosslinks, and we already know of compounds and drugs that can break other kind of crosslinks; the major problem is glucosepane, as it lasts a very long time, and, so far, nothing is known to remove it. Given that other types of crosslinks can be removed, Dr. de Grey rightly thought that there must be ways to remove (cleave) glucosepane from tissues; now, it seems that we are a step closer to that potentially becoming a reality.

If the SRF is successful in finding ways to break glucosepane crosslinks, this has huge implications for diabetes, hypertension and aging. It is great to hear that the organization is now reaching the point at which it is almost time to develop this as a therapy by creating a startup company.

It seems likely that artificial intelligence will be a necessary tool in order to reach longevity escape velocity. I was wondering how much of a role does artificial intelligence play in your research? Is this something you devote many resources to?

We don’t, but that is because other major players in this field (and good friends of mine), such as Alex Zhavoronkov and Kristen Fortney, are doing it so well already (with Insilico Med and BioAge, respectively). Check out the BioData West conference that will occur in SF a couple of days before our Undoing Aging conference in Berlin; I will be chairing a session on this.

We believe that the application of AI and, in particular, machine learning will prove to be a very valuable tool for research in the coming years. Such systems are ideally suited for high-throughput, laborious tasks that also require high attention to detail and would take humans a long time to do. Drug discovery, image analysis and many more tasks in the lab could potentially be automated, saving time and freeing up researchers to work on other critical tasks.

We are proud to have hosted the MouseAge project this year, which is an AI-based visual aging biomarker application that helps researchers determine the age of mice without the use of harmful tests. In a few months, researchers will be able to use the MouseAge application in the lab to help speed research progress up. This is just one example of how AI can be used in aging research and how the community helped to make it happen.

Given current funding, how far away from robust mouse rejuvenation do you think you are?

My estimate is 5-7 years, but that’s not quite “given current funding”. My overoptimism in saying “10 years” 13 years ago consisted entirely of overoptimism about funding – the science itself has not thrown up any nasty surprises whatsoever – but, nonetheless, I am quite optimistic as of now about funding, simply because the progress we have made has led to a whole new world of startups (including spinoffs from the SENS Research Foundation) and investors, so it’s not only philanthropy anymore. Plus, the increase in overall credibility of the approach is also helping to nurture the philanthropic side. We are still struggling, that’s for sure, but I’m feeling a lot surer that the funding drought’s days are numbered than I felt even two or three years ago.

Robust mouse rejuvenation (RMR) has long been a goal for the SENS Research Foundation, going back to when the SENS approach was initially proposed. RMR was originally outlined as being able to demonstrate and replicate SENS to double the remaining life expectancy of an already aged mouse. This would not mean the first RMR would be a total implementation of all the SENS approaches or that rejuvenation would need to be absolute; it would be a first pass to demonstrate the viability of multiple SENS approaches combined to produce robust results.

Being able to achieve a first-pass RMR could do much to convince academia that the repair approach to aging is plausible and attract more funding and interest in the approach. While RMR working in mice may not sound that exciting, it has huge implications for the field and potentially the rate of funding and progress.

How confident are you still in your previous prediction that humans will be able to control aging by 2029?

I think we’ve slipped a few years, entirely because of lack of funding. The tipping point will be when results in mice convince a critical mass of my curmudgeonly, reputation-protecting expert colleagues that rejuvenation will eventually work, such that they start to feel able to say so publicly. I think that’s on the order of five years away.

We think that the tipping point could well be if senolytics have the same result in humans as they have in mice. Enhanced tissue repair and regeneration in older people would be a very strong case for the repair approach to aging and almost certain to convince the academics sitting on the fence.

Certainly, if AGE breakers could be demonstrated to work in humans, this would also go a long way towards not only convincing academia but also grabbing public interest. Removing AGEs from the skin may potentially reverse wrinkles, for example, and restore skin elasticity, offering a very visual demonstration of repair being plausible.

There is almost certainly going to be a tipping point at which the bulk of academic and public support swings in favour of a repair approach to aging; the only question is when? Well, the sooner the basic science can be done and moved to translational research, the sooner we can all potentially benefit from these technologies. This makes supporting both the research and advocacy of rejuvenation biotechnology very important for progress.

 

About Dr. Aubrey de Grey

Dr. Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA and Ph.D. from the University of Cambridge in 1985 and 2000 respectively. His original field was computer science, and he did research in the private sector for six years in the area of software verification before switching to biogerontology in the mid-1990s. His research interests encompass the characterisation of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. He has developed a possibly comprehensive plan for such repair, termed Strategies for Engineered Negligible Senescence (SENS), which breaks aging down into seven major classes of damage and identifies detailed approaches to addressing each one. A key aspect of SENS is that it can potentially extend healthy lifespan without limit, even though these repair processes will probably never be perfect, as the repair only needs to approach perfection rapidly enough to keep the overall level of damage below pathogenic levels. Dr. de Grey has termed this required rate of improvement of repair therapies “longevity escape velocity”. Dr. de Grey 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 organisations.

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.

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

Nicola Bagalà

Steve Hill


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill discuss the progress that the SENS Research Foundation has made in tackling the aging processes. Below is a brief summary of some of the highlights of their research efforts.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 8, 2017

 

 

Today, there are many drugs and therapies that we take for granted. However, we should not forget that what is common and easily accessible today didn’t just magically appear out of thin air; rather, at some point, it used to be an unclear subject of study on which “more research was needed”, and even earlier, it was just a conjecture in some researcher’s head.

Hopefully, one day not too far into the future, rejuvenation biotechnologies will be as normal and widespread as aspirin is today, but right now, we’re in the R&D phase, so we should be patient and remind ourselves that the fact that we can’t rejuvenate people today doesn’t mean that nothing is being done or has been achieved to that end. On the contrary, we are witnessing exciting progress in basic research—the fundamental building blocks without which rejuvenation, or any new technology at all, would stay a conjecture.

In particular, SENS Research Foundation (SRF), a pioneering organization of the field, is sometimes unjustly accused by skeptics for failing to produce results. But produce results it has, and many at that. Skeptics either decide to ignore them or do not have access to reliable sources. For the benefit of the latter, we’ll discuss below what has been achieved by SRF over the past few years, in relation to the infamous “seven deadly things”, the seven categories of damage that aging causes as described in the SENS repair approach.

Mitochondrial mutations

In a nutshell, a mitochondrion is a cell component that is in charge of converting food nutrients into ATP (adenosine triphosphate), a chemical that powers cellular function. Your DNA is contained within the nucleus of each of your cells, but this isn’t the only DNA in your body; mitochondria have their own DNA (known as mtDNA), likely because, at the dawn of life, they were independent organisms that eventually entered a symbiotic relationship with eukaryotic cells, such as those found in our bodies.

Unfortunately, as mitochondria produce ATP, they also produce so-called free radicals as a byproduct—atoms with unpaired electrons that seek to “pair up” with other electrons, and to do so, they’ll gladly snatch them from other molecules nearby, damaging them. As free radicals are created by mitochondria, they’re very close to mtDNA, which is thus very susceptible to being damaged and undergoing mutations.

Mitochondria with damaged DNA may become unable to produce ATP or even produce large amounts of waste that cells cannot get rid of. To add insult to injury, mutant mitochondria have a tendency to outlive normal ones and take over the cells in which they reside, turning them into waste production facilities that increase oxidative stress—one of the driving factors of aging.

MitoSENS: How to solve this problem, and how far we’ve got

Cell nuclei are far less exposed to free-radical bombardment than mitochondria, which makes nuclear DNA less susceptible to mutations. For this reason, the cell nucleus would be a much better place for mitochondrial genes, and in fact, evolution has driven around 1000 of them there. Through a technique called allotopic expression, we could migrate the remaining genes to the nucleus and solve the problem of mitochondrial mutations.

Human-made allotopic expression was a mere theory until late 2016, when, thanks to the successful MitoSENS crowdfunding campaign on Lifespan.io, a proof of concept was finally completed. Dr. Matthew O’Connor and his team managed to achieve stable allotopic expression of two mitochondrial genes in cell culture, as reported in the open-access paper[1] they published in the journal Nucleic Acids Research. As Aubrey de Grey himself explains in this video, of the 13 genes SRF is focusing on, it’s now managed to migrate almost four. This had never been done before and is a huge step towards addressing this aspect of aging in humans. In the past few months, the MitoSENS team has presented its results around the world and worked on some problems encountered in the project.

A list of SRF-funded papers on the topic of mitochondrial mutations can be found here. A more detailed description of its intramural MitoSENS research can be found here.

Lysosomal dysfunction

Lysosomes are digestive organelles within cells that dispose of intracellular garbage—harmful byproducts that would otherwise harm cells. Enzymes within lysosomes can dispose of most of the waste that normally accumulates within cells, but some types of waste, collectively known as lipofuscin, turn out to be impossible to break down. As a result, this waste accumulates within the lysosomes, eventually making it harder for them to degrade even other types of waste; in a worst-case scenario, overloaded lysosomes can burst open and spread their toxic contents around.

This eventuality is especially problematic for cells that replicate little or not at all, such as heart and nerve cells—they’ve got all the time in the world to become swamped in waste, which eventually leads to age-related pathologies, such as heart disease and age-related macular degeneration.

LysoSENS: How to solve this problem, and how far we’ve got

As normal lysosomal enzymes cannot break down lipofuscin, a possible therapy could equip lysosomes with better enzymes that can do the job. The approach suggested by SRF originates with ERT—enzyme replacement therapy—for lysosomal storage diseases. This involves identifying enzymes capable of breaking down different types of intracellular junk, identifying genes that encode for these enzymes, and finally delivering the enzymes in different ways, depending on the tissues and cell types involved.

SRF funded a preliminary research project on lipofuscin clearance therapeutics at Rice University[2] and another project relating to atherosclerosis and the clearance of 7-ketocholesterol[3] (a lipofuscin subtype), which eventually spun into Human Rejuvenation Biotechnologies, an early-stage private startup funded by Jason Hope.

A LysoSENS-based approach is currently being pursued by Dr. Kelsey Moody, who used to work at SRF. Dr. Moody has been working on an ERT treatment for age-related macular degeneration. The treatment consists in providing cells of the macula (a region of the eye’s retina) with an enzyme capable of breaking down a type of intracellular waste known as A2E. The treatment, called LYSOCLEAR, is being worked on by Moody’s company Ichor Therapeutics, which earlier this year has announced a series A offering to start Phase I clinical trials of its product.

If LYSOCLEAR proves successful, it could pave the way for future LysoSENS-based therapies to treat lysosomal dysfunction in different tissues.

A list of SRF-funded papers on the topic can be found here.

Cellular senescence

As cells divide, their telomeres—the end-parts of chromosomes protecting them from damage—shorten. Once a critical length has been reached, cells stop dividing altogether and enter a state known as senescence. Senescent cells are known to secrete a cocktail of chemicals called SASP (Senescence Associated Secretory Phenotype), which promotes inflammation and is associated with several age-related conditions.

However, senescent cells are a bit of a double-edged sword; as explained by Professor Judy Campisi during RB2016, as long as they’re not too numerous, senescent cells carry out an anti-cancer function and may promote wound healing; however, too many of them have the opposite effect, and on top of that, they induce neighboring cells to undergo senescence themselves, starting a dangerous spiral.

Normally, senescent cells destroy themselves via programmed cell death, known as apoptosis, and are then disposed of by the immune system, but some of them manage to escape destruction, and as the immune system declines with age, this gets worse.

The result is that late in life, senescent cells have accumulated to unhealthy amounts and significantly contribute to the development of age-related diseases. Osteoarthritis, cardiovascular diseases, cancer, metabolic disorders such as diabetes, and obesity are all linked to the chronic age-related inflammation to which senescent cells contribute.

ApoptoSENS: How to solve this problem, and how far we’ve got

The proposed SENS solution is straightforward: if senescent cells become too numerous, then they need to be purged. Since they are useful in small amounts, the optimal solution would be periodically removing excess senescent cells without eradicating them entirely—and more importantly, leaving other cells unharmed.

This could potentially be achieved by either senolytic drugs or gene therapies that selectively target senescent cells and trigger programmed cell death. Indeed, a great deal of recent focus by researchers have been on finding ways to remove senescent cells using senolytic therapies.

Another approach that could complement senolytics is to address why the immune system stops clearing senescent cells effectively in the first place. This approach focuses on macrophages and other immune cells involved in clearing senescent cells, aiming to reduce inflammation so that these cells begin to function properly again. The irony is that as inflammation rises with age, the immune system that is supposed to clear senescent cells and keep inflammation levels down actually starts to create more inflammation and becomes part of the problem by not doing its job properly.

SRF has funded a number of studies on the subject of cellular senescence, and it’s recently begun working on a project in collaboration with the Buck Institute for Research on Aging, which is focusing on the immune system and its role in clearing senescent cells. Another extramural project, again with the Buck Institute, is focussed on SASP inhibition.

Senescent cell clearance has been all the rage for the past two years or so; Lifespan.io has hosted the MMTP project, which focused on testing senolytics in mice, and this was later followed by CellAge’s project to design synthetic biology-based senolytics.

There are other companies that have joined the race to add senescent cell clearance to the standard toolkit of doctors, such as Unity Biotechnology and Oisin Biotechnologies.

Unity’s approach uses a drug-based approach to senolytics and is scheduled to enter human clinical trials in 2018. A number of other research teams are also developing drug-based approaches to removing senescent cells, and the competition looks set to be fierce in this area in the coming years.

Oisin’s approach, which we discussed here, makes use of suicide genes and hopefully will be tested in clinical trials not too far into the future, thanks to venture funding presently being collected. If this system can be made to work, it will allow very selective targeting of senescent cells by destroying only those giving off a target gene or genes. Thus, if a unique gene expression profile for senescent cells is determined, it would mean only those cells were destroyed, with less risk of off-target effects.

Oisin owes its existence to the SENS Research Foundation and the Methuselah Foundation, which provided the necessary seed funding. Kizoo Technology Ventures has also invested in Oisin.

Extracellular crosslinks

The so-called extracellular matrix is a collection of proteins that act as scaffolding for the cells in our body. This scaffolding is rarely if ever replaced, and a really bad consequence of this is that its parts eventually end up being improperly linked to each other through a process called glycation—the reaction of (mainly) blood sugar with the proteins that make up the extracellular matrix itself.

The resulting cross-links impair the function and movement of the linked proteins, ultimately stiffening the extracellular matrix, which makes organs and blood vessels more rigid. Eventually, this leads to hypertension, high blood pressure, loss of skin elasticity, and organ damage, among other problems.

While there are different types of cross-links—known as AGEs, short for advanced glycation end-products—glucosepane is arguably the worst, being the most common and long-lasting of all, and the body is very ill-equipped to break it down.

GlycoSENS: How to solve this problem, and how far we’ve got

In order to eliminate unwanted cross-links, the SENS approach proposes to develop AGE-breaking molecules that may indeed sever the linkages and return tissues to their original flexibility. Of course, in order to do so, crosslink molecules need to be available for research to attempt to combat them with drugs, and especially in the case of glucosepane, this has been a problem for years.

Glucosepane is a very complex molecule, and very little of it can be extracted from human bodies, and not even in its pure form. This has been greatly hampering the progress of research against glucosepane, but thankfully, this problem is now solved thanks to a collaboration between the Spiegel Lab at Yale University and the SENS Research Foundation, which financially supported the study. It is now possible to fully synthesize glucosepane, allowing for researchers to create it on demand and at a cost-effective price.

The Spiegel Lab’s scientists are now developing anti-glucosepane monoclonal antibodies to cleave unwanted cross-links. The collaboration between the Spiegel Lab and SRF dates all the way back to 2011, but it was in 2015 that the Lab announced its success and published a related paper [4] in the journal Science.

Further information on glucosepane cross-link breakers can be found in this interview with Dr. David Spiegel from Yale University on Fight Aging!; a list of studies on the subject funded or otherwise supported by the SRF is available here.

SRF also worked with the Babraham Institute on a cross-link quantification project.

Let’s help SRF move forward

Readers who wish to donate to SRF to help the organization in its crusade against the ill health of old age can do so by contributing to its winter fundraiser or even becoming SRF patrons. Have a look at SRF’s donation page to find out more.

NB: Dr. Aubrey de Grey (Chief Science Officer and Co-founder of SENS Research Foundation) himself held an AMA (“ask me anything”) on Reddit on December 7, at 14:00 PST (22:00 UTC, 17:00 EST). The questions and Dr. de Grey’s responses can be found here.

Literature

[1] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.

[2] Gaspar, J., Mathieu, J., & Alvarez, P. (2016). A rapid platform to generate lipofuscin and screen therapeutic drugs for efficacy in lipofuscin removal. Materials, Methods and Technologies, 10, 1-9.

[3] Mathieu, J. M., Wang, F., Segatori, L., & Alvarez, P. J. (2012). Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and bioengineering, 109(9), 2409-2415.

[4] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

 

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 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.

Our Moral Obligation to Cure Aging – Aubrey de Grey Interviewed by Why? Radio

Our Moral Obligation to Cure Aging – Aubrey de Grey Interviewed by Why? Radio

Dr. Aubrey de Grey

………………………………………………………………………………………………………….

Dr. Aubrey de Grey in this interview explains and advocates for curing of aging, i.e., rejuvenation of the old to become youthful; preventing the youth from being old biologically, and other related points.

Aubrey de Grey is the U.S. Transhumanist Party’s Anti-Aging Advisor. He is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging.

This interview was conducted by Why? Radio, a program of the Institute for Philosophy in Public Life. You can also find it here.

 

 

 

LEAF Panel: How to Promote Longevity? ft. Drs. Aubrey de Grey, Alexandra Stolzing, Oliver Medvedik

LEAF Panel: How to Promote Longevity? ft. Drs. Aubrey de Grey, Alexandra Stolzing, Oliver Medvedik

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Keith Comito
Oliver Medvedik
Steve Hill
Elena Milova
Aubrey de Grey
Alexandra Stolzing
Alen Akhabaev


The U.S. Transhumanist Party is pleased to feature this extensive discussion, hosted by our allies at LEAF – the Life Extension Advocacy Foundation.

Description by LEAF: Dr. Alexandra Stolzing, Dr. Aubrey de Grey, Dr. Oliver Medvedik and a number of other guests discuss longevity, advocacy and rejuvenation biotechnology in an exclusive panel hosted by the Life Extension Advocacy Foundation (LEAF). This panel, moderated by LEAF president Keith Comito, talks about the latest progress in rejuvenation biotechnology and about how to engage, educate and excite the public regarding cutting-edge medicine.

Panel: Dr. Alexandra Stolzing, Dr. Aubrey de Grey, Dr. Oliver Medvedik , Elena Milova, Keith Comito, Steve Hill and Alen Akhabaev.

Subscribe to LEAF’s video channel for more.

Support LEAF’s work by becoming a “Lifespan Hero”: http://lifespan.io/hero

LEAF Interview with Dr. Aubrey de Grey: Controlling the Main Aging Damages

LEAF Interview with Dr. Aubrey de Grey: Controlling the Main Aging Damages

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Aubrey de Grey and Life Extension Advocacy Foundation


The U.S. Transhumanist Party is pleased to feature this interview of Dr. Aubrey de Grey, the Transhumanist Party’s Anti-Aging Advisor, conducted by Elena Milova of the Life Extension Advocacy Foundation (LEAF), one of the Transhumanist Party’s most active Allied Organizations. You can also see this interview on YouTube here.

Description by LEAF: Please enjoy this interview with Dr. Aubrey de Grey, Chief Science Officer and Co-founder of SENS Research Foundation — one of the most successful advocacy and fundraising initiatives supporting breakthrough research on the main mechanisms of aging and age-related diseases.

In this video Dr. de Grey speaks about the progress in developing interventions to tackle age-related damages identified by SENS as the main ones.

Interviewer – LEAF/Lifespan.io Board member Elena Milova.

Dr. de Grey received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. He 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.

Subscribe to Lifespan.io’s YouTube channel for more.

This interview is presented by LEAF. Please support its work by becoming a “Lifespan Hero“.

Why I Fear Aging – Article by Hayley Harrison

Why I Fear Aging – Article by Hayley Harrison

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Hayley Harrison


My mother had leukemia. I really loved her, and she really loved me. When I went to the supermarket at night, she asked me to hurry back, and said she was worried about me. She really enjoyed my company and talking to me. She could talk to me about things she couldn’t tell anyone else. It was like we were best friends. Even though my mom was 74 when she died. I was adopted when my mom was 51 and my dad was 57, so they were already older.

I was closer to her than to any member of my family. Since I lost her, I feel like I’ve lost everything. Aging made her really sick. I found out that the AML leukemia that my mom had mostly affects the elderly.

My father has been in hospital nearly two weeks. He had an operation to remove something on his lung. He’s been unwell for a few weeks now. His appetite has gone right down. He kept sleeping in the chair a lot because of the infection. He’s 81. He’s had tests to see if he has cancer, but we don’t know the results yet.

My friend told me that if my father hadn’t have had the biopsy, his chest infection would have turned into pneumonia, and that would have killed him. The antibiotics have not worked yet. So I keep thinking, “What’s going to happen to him?”. I love my father, too.

If anti-aging medicine were available now, the doctors could have treated my mother as well as my father. My mother’s leukemia was caused by aging, as I discovered. I’d love to be able to talk with my mother and father again.

I don’t want to get old, because I don’t want to get decrepit and sick. The thought of me being so shrivelled up like my parents have got terrifies me.

This is why I’m so motivated to cure aging. I’m trying to do everything I can. I keep hearing a lot that science to cure aging is underfunded. I share science articles and promote science. I’m writing this article to get the message out to all the people about getting aging under medical control.

There’s quite a few people trying to solve the aging problem. Aubrey de Grey and SENS are working on rejuvenation biotechnology. They are doing this by solving the seven deadly causes of aging. These include cell loss, junk inside and outside the cell, extracellular crosslinks, death-resistant cells, and cancerous cells.

Imagine a world where nobody gets old anymore, where everyone is young and healthy. Some people would like to do their favorite sports again, and currently they cannot because of aging.

If I lived forever, I would look to have more confidence. I would try to not be scared of people anymore.

If I were to live longer, I’d imagine I could hang out with a few of my friends in America. I enjoy fashion. I have always wanted to look like a model. I would have the time to select the best clothing and look fantastic.

Hayley Harrison is an Allied Member of the United States Transhumanist Party and the Nevada Transhumanist Party. She resides in the United Kingdom.