Tag: MitoSENS

Dr. Aubrey de Grey Accelerates His Estimates – Article by Steve Hill

Dr. Aubrey de Grey Accelerates His Estimates – Article by Steve Hill

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Steve Hill

Editor’s Note: In this article, Mr. Steve Hill highlights a recent webinar where Dr. Aubrey de Grey, the Biogerontology Advisor of the U.S. Transhumanist Party / Transhuman Party, revised his projections for the arrival of rejuvenation treatments in a more optimistic direction. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party / Transhuman Party, April 16, 2019

On January 28, 2019, we held a webinar with the SENS Research Foundation as part of a new ongoing series of research webinars. During the webinar, we asked Dr. Aubrey de Grey how close we might be to achieving robust mouse rejuvenation (RMR) and robust human rejuvenation, and his answer was somewhat surprising.

RMR is defined as reproducibly trebling the remaining lifespan of naturally long-lived (~3 years average lifespan) mice with therapies begun when they are already two years old.

Dr. de Grey now suggests that there is a 50/50 chance of achieving robust mouse rejuvenation within 3 years from now; recent interviews and conversation reveal that he’d adjusted this figure down from 5-6 years. He has also moved his estimation of this to arrive from around 20 years to 18 years for humans.

So, what is the basis for this advance in schedule? Dr. de Grey is more optimistic about how soon we might see these technologies arrive, as the level of crosstalk between damages appears to be higher than he originally anticipated a decade ago. This means that robust mouse and human rejuvenation may be easier than he previously believed.

We also asked Dr. de Grey which of the seven damages of aging was the most challenging to address. Originally, he thought solving cancer through OncoSENS methods was the biggest challenge in ending age-related diseases. However, intriguingly, he speaks about his enthusiasm for immunotherapy and how it may potentially solve the cancer issue and negate the need for Whole-body Interdiction of Lengthening of Telomeres (WILT), which was always considered a last-resort approach to shutting down cancer.

There are two main components of the WILT approach. The first is to delete telomerase-producing genes from as many cells as possible, as human cancers lengthen telomeres through one of two available pathways, and the second is to avoid the harmful consequences of our cells no longer having telomerase by periodically transplanting fresh stem cells, which have also had their telomerase-associated genes knocked out, to replace losses.

This approach has always been considered extreme, and Dr. de Grey has always acknowledged that this was the case. However, over a decade ago when Dr. de Grey and Michael Rae originally proposed this in the book Ending Aging, immunotherapy was simply not on the radar. Now, there are alternatives to WILT that show true potential and less need for radical solutions, and it is reassuring to see that Dr. de Grey is so enthusiastic about them.

He now suggests that MitoSENS is probably the most challenging to tackle of the seven types of damage in the SENS model of aging. This is no surprise given that DNA and mtDNA damage are highly complex issues to fix.

On that note, we asked Dr. Amutha Boominathan from the MitoSENS team which mitochondrial gene was their next target after they had successfully created nuclear copies of the ATP-6 and ATP-8 genes.

MitoSENS will be launching a new fundraising campaign on Lifespan.io later this year with the aim of raising funds to progress to more of the mitochondrial genes. This time, the aim will be to move the approach to an animal model and demonstrate how it could be used to correct mitochondrial defects.

Finally, if you are interested in getting involved directly with these webinars and joining the live audience, check out the Lifespan Heroes page.

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.

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

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Ariel VA Feinerman
Aubrey de Grey

This interview was originally published here. 

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 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 Aubrey de Grey, again! For those of you who are not familiar with him, here is a brief introduction.

Dr Aubrey 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.

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 short introduction to SENS research on their 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 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”.

Interview

Ariel Feinerman: Hello, Dr Aubrey de Grey!

Aubrey de Grey: Hello Ariel — thanks for the interview.

Ariel Feinerman: How do you feel 2018 year? Can you compare 2018 to 2017 or early years? What is changing?

Aubrey de Grey: 2018 was a fantastic year for rejuvenation biotechnology. The main thing that made it special was the explosive growth of the private-sector side of the field — the number of start-up companies, the number of investors, and the scale of investment. Two companies, AgeX Therapeutics and Unity Biotechnology, went public with nine-digit valuations, and a bunch of others are not far behind. Of course this has only been possible because of all the great progress that has been made in the actual science, but one can never predict when that slow, steady progress will reach “critical mass”.

Ariel Feinerman: In 2017 SENS RF have received about $7 million. What has been accomplished in 2018?

Aubrey de Grey: We received almost all of that money right around the end of 2017, in the form of four cryptocurrency donations of $1 million or more, totalling about $6.5 million. We of course realised that this was a one-off windfall, so we didn’t spend it all at once! The main things we have done are to start a major new project at Albert Einstein College of Medicine, focused on stem cell therapy for Alzheimer’s, and to broaden our education initiative to include more senior people. See our website and newsletters for details.

Ariel Feinerman: What breakthroughs of 2018 can you name as the most important by your choice?

Aubrey de Grey: On the science side, well, regarding our funded work I guess I would choose our progress in getting mitochondrial genes to work when relocated to the nucleus. We published a groundbreaking progress report at the end of 2016, but to be honest I was not at all sure that we would be able to build quickly on it. I’m delighted to say that my caution was misplaced, and that we’ve continued to make great advances. The details will be submitted for publication very soon.

Ariel Feinerman: You say that many of rejuvenating therapies will work in clinical trials within five years. Giving that many of them are already working in clinical trials or even in the clinic (like immunotherapies, cell and gene therapies) do you mean the first — maybe incomplete — rejuvenation panel, when you speak of early 2020?

Aubrey de Grey: Yes, basically. SENS is a divide-and-conquer approach, so we can view it in three overlapping phases. The first phase is to get the basic concept accepted and moving. The second phase is to get the most challenging components moving. And the third phase is to combine the components. Phase 1 is pretty much done, as you say. Phase 2 is beginning, but it’s at an early stage. Phase 3 will probably not even properly begin for a few more years. That’s why I still think we only have about a 50% chance of getting to longevity escape velocity by 2035 or so.

Ariel Feinerman: Even now many investors are fearful of real regenerative medicine approaches. For example pharmacological companies which use small molecules, like Unity Biotechnology, received more than $300 million, in much more favour than real bioengineering companies like Oisin Biotechnologies, received less than $4 million, even though the biological approach is much more powerful, cheap, effective and safe! Why is this so in your opinion, and when can we see the shift?

Aubrey de Grey: I don’t see a problem there. The big change in mindset that was needed has already occurred: rejuvenation is a thing. It’s natural that small-molecule approaches to rejuvenation will lead the way, because that’s what pharma already knows how to do. Often, that approach will in due course be overtaken by more sophisticated approaches. Sometimes the small molecules will actually work well! It’s all good.

Ariel Feinerman: Do you agree that the small-molecule approach is generally the wrong way in the future rejuvenation therapies? Because they have many flaws — especially their main mechanism via interference with human metabolism. Unlike them SENS bioengineering therapies are designed to be metabolically inert — because they just eliminate the key damage, they do not need to interfere with metabolism, so it is much easier than usual to avoid side effects and interactions with other therapies. They just eliminate the key damage, which means they are easier to develop and test — and much safer.

Aubrey de Grey: Ah, no, that’s too simplistic. It’s not true that small molecules always just “mess with metabolism” whereas genetic and enzymatic approaches eliminate damage. Small molecules that selectively kill senescent cells are absolutely an example of SENS-esque damage repair; the only thing against them is that it may be more difficult to eliminate side-effects, but that’s not because of their mode of action, it’s because of an additional action.

Ariel Feinerman: In recent years many countries gave the green light for regenerative medicine. Fast-track approval in Japan, for example, allows for emerging treatments to be used so long as they have been proven safe. The similar approach works in Russia. What about the EU or USA?

Aubrey de Grey: There’s definitely a long way to go, but the regulatory situation in the West is moving in the right direction. The TAME trial has led the way in articulating an approvable endpoint for clinical trials that is ageing in all but name, and the WHO has found a very well-judged way to incorporate ageing into its classification.

Ariel Feinerman: Do you think of working with USA Army? As far as we know they conduct research on regeneration and are very interested in keeping soldiers healthier for longer. And they have much money!

Aubrey de Grey: The Department of Defense in the USA has certainly funded a lot of high-impact regenerative medicine research for many years. I’m sure they will continue to do so.

Ariel Feinerman: Is any progress in the OncoSENS programme? Have you found any ALT genes? Is any ongoing research in WILT?

Aubrey de Grey: No — in the end that program was not successful enough to continue with, so we stopped it. There is now more interest in ALT in other labs than there was, though, so I’m hopeful that progress will be made. But also, one reason why I felt that it was OK to stop was that cancer immunotherapy is doing so well now. I think there is a significant chance that we won’t need WILT after all, because we will really truly defeat cancer using the immune system.

Ariel Feinerman: Spiegel Lab has recently published an abstract where they say they have found 3 enzymes capable of breaking glucosepane. Very exiting info! When can we hear more on their research? Revel LLC is a very secretive company.

Aubrey de Grey: They aren’t really being secretive, they are just setting up.

Ariel Feinerman: When can we see the first clinical trial of glucosepane breaker therapy?

Aubrey de Grey: I think two years is a reasonable estimate, but that’s a guess.

Ariel Feinerman: What do you think of the Open Source approach in rejuvenation biotechnology? The computer revolution in the early 2000s has taken place only because Open Source caused an explosion in software engineering!

We have many examples when Big Pharma buys a small company which has patents on technology and then cancels all research. In the Open Source approach you cannot “close” any technology, while everyone can contribute, making protocol better and everyone can use that without any licence fee! Anyway, there are countries where you cannot protect your patents. Maybe it will be better to make technology open from the beginning?

Famous biohacker Josiah Zayner said: “In the gene therapy world most treatments are easy to replicate or pirate because you can reverse engineer the DNA from scientific papers or patents. Same exact treatment, same purity and quality I could give to someone rejected from the clinical trial. The cost? Hundreds or a few thousand dollars at most. Same deal with immunotherapy.”

Aubrey de Grey: I think you’ve pretty much answered your own question with that quote. The technologies that will drive rejuvenation are not so easy to suppress.

Ariel Feinerman: Is the SENS RF going to begin new research programmes in 2019?

Aubrey de Grey: Sure! But we are still deciding which ones. We expect that our conference in Berlin (Undoing Aging, March 28–30) will bring some new opportunities to our attention.

Ariel Feinerman: What are your plans for 2019?

Aubrey de Grey: I’d like to say less travelling, but that doesn’t seem very likely at this point. Really my goal is just to keep on keeping on — to do all I can to maintain the growth of the field and the emerging industry.

Ariel Feinerman: Thank you very much for your answers, hope to see you again!

Aubrey de Grey: My pleasure!

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. If you like Ariel’s work, any help would be appreciated via PayPal: arielfeinerman@gmail.com.

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

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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.