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The Longevity Film Competition – Announcement by SENS Research Foundation, The Healthy Life Extension Society, and International Longevity Alliance

The Longevity Film Competition – Announcement by SENS Research Foundation, The Healthy Life Extension Society, and International Longevity Alliance

SENS Research Foundation
The Healthy Life Extension Society 
International Longevity Alliance


Editor’s Note: The U.S. Transhumanist Party encourages its members to participate in the Longevity Film Competition, whose official website can be found here. The more original attempts exist to convey to the general public the feasibility and desirability of indefinite life extension, and to dispel common misconceptions about it, the sooner we will have the critical mass of public support needed to bring about this most vital goal. 

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, July 15, 2018


Contest Introduction: 

We are living in very interesting times, times of constant change. The scientific community is telling us that soon we could enjoy much healthier and longer lives thanks to technological advancements happening at an accelerated rate. The future can be bright and healthy, and we want more people to know about this amazing prospect and want them to get involved in this important mission – the mission of healthy longevity.

However, describing something potentially beautiful is not always easy. We think you can help by making a (very) short movie conveying that a longer and healthier life thanks to sustainable medical interventions, will be a very positive thing for citizens and society alike.

Help us spread the word in the right way, help us make sure people understand this is about health and that for the first time in history the possibility of tackling aging is not science fiction, but science fact.

Join us in this crusade by entering our competition presented by the SENS Research Foundation, The Healthy Life Extension Society and the International Longevity Alliance and not only potentially help saving lots of lives, but also win the first prize of $10,000!

We look forward to your ideas on how to better communicate this important message to the world.

– The Longevity Film Competition team

Contest Guidelines: 

Even though putting aging under medical control is probably desirable to most humans, this concept is not always clear to everybody.

One of our goals is to use this competition as a vehicle to clarify and demystify some of the misconceptions we hear very often.

You can choose just one or all of them and explain them in any way you choose, using your own language and ideas.

Misconception #1

“Aging and disease are two separate things.”

CLARIFICATION:

— Aging causes disease, and they should be treated as one. —

As we age, we lose our health. We cannot age and become elderly without eventually getting ill as a result of it. If we live long enough, we will all get sick of one or several of the diseases of aging and eventually succumb to them. When we talk about eliminating aging, we talk about putting this process under medical control so that we don’t have to get sick as we age.

Misconception #2

“If I live to a 150, I will be living for a long time in an old, sick body.”

CLARIFICATION:

— If these new therapies help us live to a 150, it will only be because they will keep us strong and healthy. —

When we talk about extending our lifespan, we are talking about extending our health. The extension of our life will not happen unless we fix the health problems that come with aging. Once we do this, more longevity will happen as a “side benefit” of being healthier. As we said before, we get sick with aging, and that’s why most of humans die of old age.

So, if we will still be alive at 150, this will mean we will have a better control of the aging process through medical interventions – hence we should not be living in an old sick body.

Misconception #3

“Aging is natural, and we shouldn’t tamper with the natural.”

CLARIFICATION:

— Combating aging is a great challenge for Humanity, and we have a long history of getting great benefit from tampering with many natural things. —

It is proven that there are endless ‘unnatural’ things created by humans of enormous value and positive outcomes, and we can imagine only a minuscule number of people who would choose to live without them — especially when it has to do with suffering, disease and death.

A few examples of unnatural things we use all the time without questioning much are: pacemakers, antibiotics (to kill natural bacteria), painkillers, cochlear implants, dialysis, plastic surgery, airplanes (it is not natural for us to fly), hair coloring, prosthetic limbs, contact lenses, birth-control methods, and the list goes on forever.

On the other hand, here are some natural things that are definitely bad for us: earthquakes, hurricanes, mudslides, tornadoes, infectious microorganisms, poisonous plants, predators, venomous creatures, fire, gravity (when we fall), tsunamis, radiation, meteor impacts, etc.

It is time to reason and understand that “natural” doesn’t necessarily mean “good”.

Misconception #4

“These therapies will only be for the rich.”

CLARIFICATION:

— Healthy longevity therapies are being developed for everybody to access. —

Rejuvenation therapies could be as little reserved for rich people as mobile phones, cars, electricity, or vaccination may have been in the beginning. Like for most technological progress, the research may be complicated and expensive, but once the technology becomes available, it will become available for everybody. One good example is that the first Human Genome took $2.7 billion dollars and almost 15 years to complete. In 2001 the price of sequencing a genome was 100 Million dollars; today is under 1000 dollars, and it will keep going down without a doubt. Humanity has never stopped advancing just because it was harder and less cost-effective in the beginning; if we had thought like that, we would probably not have most of the technology that is available for everybody today. That’s one more reason why it’s so important not to delay the development of these cures.

Official Rules

  1. Concept of film: The submitted piece should show that medical progress for a healthier and longer life is generally a good thing for citizens and society alike. You will achieve this by using the list of common misconceptions provided in the Guidelines section above. You must choose at least one and may also choose all of them.
  2. Length: The length of the film should be a minimum of 1 minute and a maximum of 20 minutes.
  3. Visual art style: All kinds of visuals are allowed:
    Films, computer animations, whiteboard drawings, live action, infographics, stop and motion, cartoons, typography, screencast, etc.
  4. Genre: All genres are allowed. Science, fiction or science-fiction, a story, sad or funny, a docufiction, a documentary, etc.
  5. Copyright: All material used in the video should be original, or you should own the copyright for it. You may not use copyrighted material for which you don’t have the rights. If you fail to follow this rule, your film will be automatically disqualified.
  6. Submission: The submission deadline is 23:59 GMT September 15, 2018. The final work should be uploaded to the Internet, and a link to watch it should be provided to us via email at contact@longevityfilmcompetition.com, together with your last name, first name, and the proposed title of the work. The winners will be announced October 1st (International Longevity Day).
  7. Language: The official language is English. Videos can also be submitted in French, Spanish, Italian, German, Russian and Dutch but would need to have English subtitles.
  8. Work Originality and Permissions: a) Films must be the original work of the applicants, and they must be unpublished before July 1st, 2018. b) If a film is based upon another person’s life or upon a book or other underlying work, applicant(s) must secure any necessary rights to make such adaptations. c) By entering the competition, you represent that you have secured all necessary rights. d) Applicants are solely responsible for obtaining all necessary rights and permissions for third-party materials included in their films, including but not limited to music, trademarks, logos, copyrights, and other intellectual property rights. e) Longevity Film Competition (LFC) expressly disclaims all liability or responsibility for any violations of the foregoing. f) If your submission is selected for a prize, you agree that SENS Research Foundation (SRF), The Healthy Life Extension Society (Heales), and the International Longevity Alliance (ILA) use your movie without restriction to promote the mission of curing the diseases of aging. SRF, Heales and the ILA can show your work on the internet or by all other means. g) SRF, Heales and the ILA are non-profit organizations and may use the films to drive donations from the public, which will be used to advance the mission of healthy longevity. Any funds raised though the films will support scientific research, outreach, and/or education programs.
  9. Selected Films and Winners: a) LFC has no obligation (other than as stated in these rules or on our website) to disclose any of the following information: i) identities of screeners or judges; ii) notes, feedback, or information relating to the submitted project; and/or iii) details regarding the submission review or selection process. b) LFC explicitly disclaims any liability or responsibility for any comments, notes, or opinions expressed about a submission, whether by LFC or by its volunteers.  c) Winners will be announced on October 1st, 2018. The judges’ decision is final. Winners receiving cash prizes are solely responsible for payment of all applicable local, state, and federal taxes.
  10. Legal action: In the event of litigation the competent courts will be those of the Brussels jurisdiction in Belgium.
  11. Additional information: For all issues not mentioned above, the members of the jury will decide. They must decide in equity and with the same rules for all competitors.

COMPETITION LEGAL TERMS

BY SUBMITTING THE MATERIAL PARTICIPANTS  AGREE:

To having read all of the rules, understood, and have complied with these rules.

To warrant that their work is original and that there are no disputes regarding the ownership of their submission.

To warrant that the submitted material does not defame or invade the rights of any person living or dead.

That failure to adhere to the competition rules and regulations will result in disqualification.

That no revisions of materials will be accepted once entry has been submitted.

That to the best of their knowledge, all the statements herein are true and correct.

TO INDEMNIFY, HOLD HARMLESS, AND DEFEND THE COMPETITION, ITS EMPLOYEES, VOLUNTEERS, DIRECTORS, JURORS, REPRESENTATIVES, AND AFFILIATES FROM ALL LIABILITY, CLAIMS, AND DAMAGES IN CONNECTION WITH THE SUBMISSION AND FROM ANY FEES AND EXPENSES, INCLUDING BUT NOT LIMITED TO REASONABLE ATTORNEYS’ FEES, THAT ANY OF THEM MAY INCUR IN CONNECTION THEREWITH.
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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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.