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Aubrey de Grey – Towards the Future of Regenerative Medicine

Why is aging research important? Biological aging causes suffering, however in recent times there as been surprising progress in stem cell research and in regenerative medicine that will likely disrupt the way we think about aging, and in the longer term, substantially mitigate some of the suffering involved in growing old.
Aubrey de Grey is the Chief Science Officer of SENS Foundation – an organisation focused on going beyond ageing and leading the journey towards  the future of regenerative medicine!  
What will it take to get there?
 


You might wonder why pursue  regenerative medicine ?
Historically, doctors have been racing against time to find cures for specific illnesses, making temporary victories by tackling diseases one by one – solve one disease and another urgency beacons – once your body becomes frail, if you survive one major illness, you may not be so lucky with the next one – the older you get the less capable your body becomes to staving off new illnesses – you can imagine a long line of other ailments fading beyond view into the distance, and eventually one of them will do you in.  If we are to achieve  radical healthy longevity , we need to strike at the fundamental technical problems of why we get frail and more disease prone as we get older.  Every technical problem has a technical solution – regenerative medicine is a class of solutions that seek to keep turning the ‘biological clock’ back rather than achieve short-term palliatives.

The damage repair methodology has gained in popularity over the last two decades, though it’s still not popular enough to attract huge amounts of funding – what might tip the scales of advocacy in damage-repair’s favor?
A clear existence proof such as achieving…

Robust Mouse Rejuvenation

In this interview, Aubrey de Grey reveals the most amount of optimism I have heard him express about the near term achievement of Robust Mouse Rejuvenation.  Previously it’s been 10 years away subject to adequate funding (which was not realised) – now Aubrey predicts it might happen within only 5-6 years (subject to funding of course).  So, what is Robust Mouse Rejuvenation – and why should we care?

For those who have seen Aubrey speak on this, he used to say RMR within 10 years (subject to funding)

Specifically, the goal of RBR is this:  Make normal, healthy two-year old mice (expected to live one more year) live three further years. 

  • What’s the ideal type of mouse to test on and why?  The ideal mouse to trail on is one that doesn’t naturally have a certain kind of congenital disease (that might on average only live 1.5 or 2 years) – because increasing their lifespan might only be a sign that you have solved their particular congenital disease.  The ideal type of mouse is one which lives to 3 years on average, which could die of various things.
  • How many extra years is significant? Consistently increasing mouse lifespan for an extra two years on top of their normal three year lifespans – essentially tripling their remaining lifespan.
  • When, or at what stage of the mice’s life to begin the treatment? Don’t start treating the mice until they are already 2 years old – at a time where they would normally be 2 thirds of the way though their life (at or past middle age) and they would have one more year to live.

Why not start treating the mice earlier?  The goal is to produce sufficiently dramatic results in a laboratory to convince the main-stream gerontology community, such that they would willingly publicly endorse the idea that it is not impossible, but indeed it is only a matter of time before rejuvenation therapy will work in humans – that is to get out there on talk shows and in front of cameras and say all this.

Arguably, the mainstream gerontology community are generally a bit conservative – they have vested interests in being successful in publishing papers, they get grants they have worries around peer review, they want tenure, and have a reputation to uphold.   Gerontologists hold the keys to public trust – they are considered to be the authorities on aging.
When gerontologists are convinced and let the world know about it, a lot of other people in the scientific community and in the general community will also then become convinced.  Once that happens, here’s what’s likely to happen next – longevity through rejuvenation medicine will become a big issue, there will be domino effects – there will be a war on aging, experts will appear on Oprah Winfrey, politicians will have to include the war on aging in their political manifesto if they want to get elected.

Yoda - the oldest mouse ever to have lived?
Yoda, a cute dwarf mouse, was named as the oldest mouse in 2004 at age 4 who lived with the much larger Princess Leia, in ‘a pathogen-free rest home for geriatric mice’ belonging to Dr. Richard Miller, professor of pathology in the Geriatrics Center of the Medical School. “Yoda is only the second mouse I know to have made it to his fourth birthday without the rigors of a severe calorie-restricted diet,” Miller says. “He’s the oldest mouse we’ve seen in 14 years of research on aged mice at U-M. The previous record-holder in our colony died nine days short of his 4th birthday; 100-year-old people are much more common than 4-year-old mice.” (ref)

What about Auto-Immune Diseases?

Auto-immune diseases (considered incurable to some) – get worse with aging for the same reason we loose general ability to fight off infections and attack cancer. Essentially the immune system looses it’s precision – it has two arms: the innate system and the adaptive – the adaptive side works by having polyclonality – a very wide diversity of cells with different rearrangements of parts of the genome that confer specificity of the immune cell to a particular target (which it may or may not encounter at some time in the future) – this polyclonality diminishes over life such that the cells which are targeted towards a given problem with the immune system are on average less precisely adapted towards it – so the immune system takes longer to do it’s job or doesn’t do it effectively – so with autoimmune system it looses it’s ability to distinguish between things that are foreign and things that are part of the body. So this could be powerfully addressed by the same
measures taken to rejuvenate the immune system generally – regenerating the thyamis and illuminating senescent cells that are accumulating in the blood.

Big Bottlenecks

See Aubrey discuss this at timepoint: 38:50
Bottlenecks: which bottlenecks does Aubrey believes need most attention from the community of people who already believe aging is a problem that needs to be solved?

  1. The first thing: Funding. The shortage of funding is still the biggest bottleneck.
  2. The second thing: The need for policy makers to get on board with the ideas and understand what is coming – so it’s not only developing the therapies as quickly as possible, it’s also important that once they are developed, the therapies get disseminated as quick as possible to avoid complete chaos.

It’s very urgent to have proper discussions about this.  Anticipating the anticipation – getting ready for the public anticipating these therapies instead of thinking that it’s all science fiction and is never going to happen.

 

Effective Advocacy

See Aubrey discuss this at timepoint: 42:47
Advocacy, it’s a big ask to get people from extreme opposition to supporting regenerative medicine. Nudging people a bit sideways is a lot earlier – that is getting them from complete offense to less offense, or getting people who are un-decided to be in favor of it.

Here are 2 of the main aspects of advocacy:

  1. feasibility / importance – emphasize progress, embracement by the scientific community (see paper hallmarks of aging – single most highly cited paper on the biology of aging this decade) – defining the legitimacy of the damage repair approach – it’s not just a crazy hair brained idea …
  2. desirability – concerns about (bad arguments : on overpopulation – oh don’t worry we will immigrate into space – the people who are concerned about this problem aren’t the ones who would like to go to space) – focus on more of the things that can generalize to desirable outcomes – so regenerative medicine will have side effects, like a longer lifespan, but also people will be more healthy at any given age compared to what they would be in they hadn’t had regenerative therapy – no body wants Alzheimer’s, or heart disease – if the outcome of regenerative medicine is that then it’s easier to sell.

We need a sense of proportion on possible future problems – will they generally be more serious than they are today?
Talking about uploading, substrate independence, etc one is actively alienating the public – it’s better to create a foundation of credibility in the conversation before you decide to persuade anyone of anything.  If we are going to get from here to the long term future we need advocacy now – the short term matters as well.

More on Advocacy here:

And here

Other Stuff

This interview covers a fair bit of ground, so here are some other points covered:

– Updates & progress at SENS
– Highlights of promising progress in regenerative medicine in general
– Recent funding successes, what can be achieved with this?
– Discussion on getting the message across
– desirability & feasibility of rejuvenation therapy
– What could be the future of regenerative medicine?
– Given progress so far, what can people alive today look forward to?
– Multi-factorial diseases – Fixing amyloid plaque buildup alone won’t cure Alzheimer’s – getting rid of amyloid plaque alone only produced mild cognitive benefits in Alzheimer’s patients. There is still the unaddressed issue of tangles… If you only get rid of one component in a multi-component problem then you don’t get to see much improvement of pathology – in just he same way one shouldn’t expect to see much of an overall increase in health & longevity if you only fix 5 of 7 things that need fixing (i.e. 5 of the 7 strands of SENS)
– moth-balling anti-telomerase approach to fighting cancer in favor of cancer immunotherapy (for the time being) as it’s side effects need to be compensated against…
– Cancer immunotherapy – stimulating the bodies natural ability to attack cancer with it’s immune system -2 approaches – car-T (Chimeric Antigen Receptors and T cells), and checkpoint inhibiting drugs.. then there is training the immune system to identify neoantegens (stuff that all cancers produce)

Biography

Chief Science Officer, SENS Research Foundation, Mountain View, CA – http://sens.org

AgeX Therapeutics – http://www.agexinc.com/

Dr. Aubrey de Grey is a biomedical gerontologist based in Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) biomedical research charity that performs and funds laboratory research dedicated to combating the aging process. He is also VP of New Technology Discovery at AgeX Therapeutics, a biotechnology startup developing new therapies in the field of biomedical gerontology. In addition, he is Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA in computer science and Ph.D. in biology from the University of Cambridge. His research interests encompass the characterisation of all the types of self-inflicted cellular and molecular damage that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. 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. He is a highly sought-after speaker who gives 40-50 invited talks per year at scientific conferences, universities, companies in areas ranging from pharma to life insurance, and to the public.

 

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Longevity Day with Aubrey de Grey!

“Longevity Day” (based on the UN International Day of Older Persons – October 1) is a day of support for biomedical aging and longevity research. This has been a worldwide international campaign successfully adopted by many longevity activists groups. In this interview Aubrey de Grey lends support to Longevity Day and covers a variety of points, including:
– Updates: on progress at SENS (achievements, and predictions based on current support), funding campaigns, the recent Rejuvenation Biotechnology conference, and exciting news in health and medicine as it applies to longevity
– Advocacy: What advocates for longevity research need to know
– Effective Altruism and Science Philanthropy – giving with impact – cause prioritization and uncertainty – how to go about measuring estimates on impacts of dollars or units of effort given to research organizations
– Action: High impact areas, including more obvious steps to take, and some perhaps less obvious/underpopulated areas
– Leveraging Longevity Day: What to do in preparation to leverage Longevity Day? Once one has celebrated Longevity Day, what to do next?

“Longevity Day” (based on the UN International Day of Older Persons – October 1st) is a day of support for biomedical aging and longevity research. This has been a worldwide international campaign successfully adopted by many longevity activists groups.

Here is the Longevity Day Facebook Page.

longevity-advocacy-action-aubrey-de-grey-longevity-day-oct-1st

Strategies for Engineered Negligible Senescence with Aubrey de Grey

Projects at SENS Foundation

aubrey-de-grey-stragegies-for-engineered-negligable-senescenceSens Foundation has a lot of projects that were working on all at the same time.  There are 3 projects that we are working on at our research center in California and then there are a whole bunch of others that we support at university laboratories around the world – mostly in the USA.
In the research center in Mountain View California there are 3 projects that we are working on:

  1. 1st of all, mitochondrial mutation – we’re interested in combating the accumulation of mitochondrial mutations, not actually via repairing them, but by making them harmless; by putting modified copies of the mitochondrial genes into the nuclear dna, modified in such a way that the proteins go back to the right place – even though the dna is in the wrong place. This is an idea that was actually pioneered in Australia by a group in Monash University – about 25 or 27 years ago even.  But has actually been very challenging to make work in general.  Over the last few years a number of breakthroughs have been made to make the whole thing much more realistic, and we’re perusing that with a lot of energy now.
  2. The 2nd thing we’re working on at the research center is to identify enzymes from the environment (especially from bacteria) that can break down substances whose accumulation in the body over life causes diseases like cardiovascular disease and macular degeneration. We’ve become quite good at finding enzymes that break down these substances, and now were developing ways to put them into mammalian cells in manners that actually allow the cells to survive longer.  We’ve just published in the April of 2012 the first demonstration of rescue of cells from toxic substances that accumulate in the body using a system of this nature.
  3. The 3rd thing we are doing at the research center is part of our cancer project – we’re interested in combating cancer by controlling the elongation of ends of chromosomes – these things called ‘telomeres‘ and were working specifically on a rather neglected area in that field called ALT (Alternative Lengthening of Telomeres) which is a method that about 10% of cancers use that is still very characterized genetically and we’re working on that.

Video interview here:

Medical Bioremediation

The elimination of this junk which accumulates inside cells using enzymes from bacteria is what we call medical bioremediation. We call it that because bioremediation is the use of very much the same method to eliminate pollutants from the environment as a method of environmental decontamination.
Bioremediation works extremely well; it’s not just an academic idea; it’s a thriving commercial discipline. And it certainly shows us that it’s pretty straight forward to find enzymes to break down more-or-less whateever you want so long as the thing you want to break down is organic, and rich in energy – so that the microbe can break it down and it can live off it.

The Divide & Conquer Approach to Solving Aging

Most of the work going on that is related to SENS is not directly related to longevity. And that’s because the SENS approach to combating aging is a ‘divide and conquer’ approach; an approach in which we split the problem of aging into a number of sub-problems and we address each of those individually.
In any divide an conquer approach to a complex technological problem you don’t expect to see any actual results in terms of the overall goal of the technology until all of the components are at least working reasonably well. And we’re certainly not at that stage yet. So yes, there’s masses of progress at SENS in various of the strands that we’ve been perusing – but that has not yet translated into a longevity benefit yet in any species. However there is plenty of work going on in simpler strategies to combat aging; strategies that we don’t pursue because they won’t scale – they will only give you a modest benefit postponing the diseases and disabilities of old age.
But which we’re very much happy for other people to pursue in because they may be easier to implement in human beings than the SENS approach. So, for example a few years ago it was discovered that the drug named Rapamycin was able to significantly extend the life-span of rodents – which is quite a surprise because the drug had been around a long time. But you know there have been a lot of studies of how that happens ever since that time – and we may be able to turn that into a useful therapy for human beings.
There is still a lot of excitement around drugs that emulate calorie restriction that extends lifespan of rodents especially, by tricking them (essentially) into thinking they are in a famine when they’re not. And of course there’s a lot of work going on still in trying to evaluate other approaches to combating aging by simple methods – there is always constantly new news in this area.

Will Any of the SENS Approaches Work in Isolation?

More videos about SENS can be browsed through in this playlist:

Strategies for Engineered Negligible Senescence (SENS) is the term coined by British biogerontologist Aubrey de Grey for the diverse range of regenerative medical therapies, either planned or currently in development,[1] for the periodical repair of all age-related damage to human tissue with the ultimate purpose of maintaining a state of negligible senescence in the patient, thereby postponing age-associated disease for as long as the therapies are reapplied.[2]

The term “negligible senescence” was first used in the early 1990s by professor Caleb Finch to describe organisms such as lobsters and hydras, which do not show symptoms of aging. The term “engineered negligible senescence” first appeared in print in Aubrey de Grey’s 1999 book The Mitochondrial Free Radical Theory of Aging,[3] and was later prefaced with the term “strategies” in the article Time to Talk SENS: Critiquing the Immutability of Human Aging[4] De Grey called SENS a “goal-directed rather than curiosity-driven”[5] approach to the science of aging, and “an effort to expand regenerative medicine into the territory of aging”.[6] To this end, SENS identifies seven categories of aging “damage” and a specific regenerative medical proposal for treating each.

[1]Research Themes (February 4, 2013) http://www.sens.org/research/introduction-to-sens-research

[2] de Grey, Aubrey; Rae, Michael (September 2007). Ending Aging: The Rejuvenation Breakthroughs that Could Reverse Human Aging in Our Lifetime. New York, NY: St. Martin’s Press, 416 pp. https://www.amazon.com/Ending-Aging-Rejuvenation-Breakthroughs-Lifetime/dp/0312367074

[3] de Grey, Aubrey (November 2003). The Mitochondrial Free Radical Theory of Aging. Austin, Texas: Landes Bioscience. ISBN 1-58706-155-4. http://www.sens.org/files/pdf/MiFRA-06.pdf

[4] de Grey AD, Ames BN, Andersen JK, Bartke A, Campisi J, Heward CB, McCarter RJ, Stock G (April 2002). “Time to Talk SENS: Critiquing the Immutability of Human Aging”. Annals of the New York Academy of Sciences 959: 452–62. http://www.sens.org/files/pdf/manu12.pdf

[5] Bulkes, Nyssa (March 6, 2006). “Anti-aging research breakthroughs may add up to 25 years to life”. The Northern Star. Northern Illinois University (DeKalb, USA). http://northernstar.info/city/anti-aging-research-breakthroughs-may-add-up-to-years-to/article_a4d2acd9-475d-5e12-a81c-77011f9c65ad.html http://www.worldhealth.net/news/anti-aging_research_breakthroughs_may_ad/

[6] “Age-Related Diseases: Medicine’s Final Adversary?”. Huffington Post Healthy Living. http://www.huffingtonpost.com/aubrey-de-grey-phd/age-related-diseases_b_985019.html

Aubrey de Grey – Artificial Organs as Replacement Parts to aid in Defeating Aging

Aubrey de Grey discusses using artificial organs and synthetic devices as replacement parts to aid in defeating aging. (Also see this interview where Aubrey discusses some of the various approaches that SENS therapy will likely be delivered.)


Replacing a failing organ with a healthy one can sidestep the need for the various SENS therapies for that organ only – however there are two limitations – 1) much of the body is made up of non-transplantable organs, 2) transplanting organs or tissue engineering involves invasive surgery, something that involves risks if it is done too much.
Organ transplantation/Tissue engineering is useful today and will be useful when early forms of SENS delivery become available – however there will continue to be a very high priority in approaches that mitigate the need for invasive organ transplantation.
Non-biological organs are useful today – for instance the cochlear implant – and there will continue to be a place for them. Though in the long run biological organs will likely work more effectively because they are ‘evolved’ for that purpose.


Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections:

Superlongevity – Mini Documentary

Short documentary on longevity science going mainstream and surrounding public opinion – with some key folk in the transhumanist movement discussing the issues around aging and the state of play, how to think rationally about aging and longevity medicine, media performance, common objections to longevity technology, advocacy, how the public may come to terms with and ultimately accept longevity technology.

I hope to be developing this documentary further in the near future.

Starring : Aubrey de Grey, Max More, Michael Shermer, George Dvorsky, David Pearce and Ramez Naam.

Ramez NaamRamez Naam is a professional technologist and science fiction writer. He was involved in the development of widely used software products such as Microsoft Internet Explorer and Microsoft Outlook. His last role at Microsoft was as a Partner Group Program Manager in Search Relevance for Live Search.  Naam currently holds a seat on the advisory board of the Acceleration Studies Foundation, is a member of the World Future Society, a Senior Associate of the Foresight Institute, and a fellow of the Institute for Ethics and Emerging Technologies.

MAx1Max More is a philosopher and futurist who writes, speaks, and consults on advanced decision-making about emerging technologies.  Founder of the Extropy Institute, Max More has written many articles espousing the philosophy of transhumanism and the transhumanist philosophy of Extropianism, most importantly his Principles of Extropy.  At the start of 2011, Max More became president and CEO of the Alcor Life Extension Foundation, an organization he joined in 1986.

Michael-Shermer1-500x500_cMichael Brant Shermer is a science writer, historian of science, founder of The Skeptics Society, and Editor in Chief of its magazine Skeptic, which is largely devoted to investigating pseudoscientific and supernatural claims. The Skeptics Society currently has over 55,000 members. Shermer also engages in debates on topics pertaining to pseudoscience and religion in which he emphasizes scientific skepticism.

David Pearce - Healesville SanctuaryDavid Pearce is a British philosopher who promotes the idea that there exists a strong ethical imperative for humans to work towards the abolition of suffering in all sentient life. His book-length internet manifesto The Hedonistic Imperative outlines how technologies such as genetic engineering, nanotechnology, pharmacology, and neurosurgery could potentially converge to eliminate all forms of unpleasant experience among human and non-human animals, replacing suffering with gradients of well-being, a project he refers to as “paradise engineering”.

aubreyeagleAubrey de Grey is an English author and biomedical gerontologist, currently the Chief Science Officer of the SENS Research Foundation. He is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging (1999) and co-author of Ending Aging (2007). He is known for his view that medical technology may enable human beings alive today to live indefinitely

George Dvorsky San FranGeorge Dvorsky is a Canadian bioethicist, transhumanist, and futurist. He is a contributing editor at io9 and producer of the Sentient Developments blog and podcast. Dvorsky currently serves as Chair of the Board for the Institute for Ethics and Emerging Technologies (IEET) and is the founder and chair of the IEET’s Rights of Non-Human Persons Program, a group that is working to secure human-equivalent rights and protections for highly sapient animals.

 


 

All footage footage is either my own, is news under ‘fair use’ (in line with the 4 factors of fair use) or I have permission from the owners.

Stay tuned, as there will be further updates.

Current version: v1.0 (video)

Previous versions:
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Aubrey de Grey – Engaging the Disengaged

There is likely a lot of mileage in engaging the disengaged in untapped support for more efficient progress in regenerative medicine. We need to talk about the familiar and positive aspects of rejuvenation medicine!

Aging issues have appeared in the media a lot recently – all to often the narrative is skewed in the direction of sci-fi sounding future scenarios, and are embedded in sensationalized media stunts, to the effect that for many the ideas ‘go out one ear and out the other’ – the people whom are currently disengaged forget about rejuvenation medicine and loose interest when they hear about the latest patch for their iphone.

There are a lot more people out there in the world besides transhumanists who have resources and energy to transform into meaningful progress in the science of rejuvenation biotechnology.
People also get fixated on long term Malthusian visions or the pseuodoscientific and religious connotations of words like ‘immortality’ and loose sight of the fact that SENS and others are working on _health_.

History shows a bleak picture, but the further back we go, the worse it seems. It seems civilization is getting better at healthy living into older age – now it really is a priority to get better at getting better – effective aging, so to speak.
There is so much in the world to do – many people grow old and unable to do the things they want to do before they have finished doing much of what they want to do. Live is precious – it’s an imperative that we focus on giving people extra healthy life-time for them to do more of the things they love to do.

Aubrey-de-Grey-Engaging-the-Disengaged

The main thing that people misunderstanding is the actual relationship between aging and the diseases of old age – and this is largely the fault of gerontologists….people would go out and say, all the time, ‘Aging is not a disease’ – that’s not useful. Ultimately it’s very counter productive. What happened was people would think to themselves ‘well ok then, aging is this natural thing that’s never going to be amenable to medical intervention, because it’s not a disease – and also because it’s not a disease, then why should we care about it?’ – so it was absolutely the wrong thing to be saying… it’s even more the wrong thing to be saying because it’s not even true. Aubrey de Grey

Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections:

Aubrey de Grey – Ageing & Suffering

The main thing that people misunderstanding is the actual relationship between aging and the diseases of old age – and this is largely the fault of gerontologists….people would go out and say, all the time, ‘Aging is not a disease’ – that’s not useful. Ultimately it’s very counter productive. What happened was people would think to themselves ‘well ok then, aging is this natural thing that’s never going to be amenable to medical intervention, because it’s not a disease – and also because it’s not a disease, then why should we care about it?’ – so it was absolutely the wrong thing to be saying… it’s even more the wrong thing to be saying because it’s not even true. Aubrey de Grey

 

Aubrey-de-Grey---Ageing-&-Suffering

 


Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections:

Aubrey de Grey – SENS Therapy Delivery

In this interview Aubrey discusses some of the various approaches that SENS therapy will likely be delivered. Mostly covering gene therapy. Also see this interview where Aubrey de Grey discusses using artificial organs and synthetic devices as replacement parts to aid in defeating aging.

Ex-Vivo Gene Therapy

Ex Vivo Gene Therapy

ref: yolasite.com (click for larger image)

Some things that people are already looking at, for instance introducing new blood stem cells into AIDS patients that contain an AIDS resistant gene named CCR5. A very small portion of people have a natural variant of that gene, called Delta32, which confers very strong resistance to HIV. If you could give this variant of CCR5 this could be a very powerful therapy – luckily the cells that need to have that variant are blood cells – blood cells come from stem cells – so bone marrow transplants with this appropriately modified version of this gene would be very powerful, and that is already being worked on.
There may be very many other cases of inherited diseases (especially) which could be modified and indeed perhaps cured by using genetic modification of stem cells for stem cell therapy.
Now in the case of ageing, this may also be a good way of delivering certain of the SENS therapies – the one that’s most obvious is LysoSENS – the Lyso Enhancement idea for getting rid of the molecular garbage inside of cells – because here we have to introduce new enzymes into these cells (enzymes that are not encoded into the normal human genome) and in some cases it may make sense to actually introduce the enzymes by injecting the enzymes into the circulation in the same way we already treat certain inherited diseases of Lysosomal function (called Lysosomal storage diseases). But in other cases it may be actually be preferable to make genetic modifications to stem cells so that the blood cells or the other cells that are created from those stem cells are able to have that genetic modification and thereby not to accumulate the molecular garbage that we are talking about – perhaps even to eliminate the molecular garbage that had already accumulated.

Somatic Gene Therapy

In_vivo_gene_therapy

ref: yolasite.com (click for larger image)

Some of what were going to need to do in genetic modification of people so as to implement SENS will not, or almost certain not be able to be implemented using ex-vivo gene therapy – the genetic modification of cells outside the body that are then introduced into the body. Some of it is going to have to be done by genetically modifying cells in the body itself. That is what is called ‘Somatic Gene Therapy’ – the way it’s normally done is by engineering a virus contain the engineered DNA that we are interested in and not to contain the DNA that the virus naturally has that makes it bad for us*. And of course gene therapy as an idea has been around for quite a long time – and in fact the first clinical trials of gene therapy happened about 20 years ago. But it’s had a pretty rocky ride because in fact there is an awful lot of risks involved in gene therapy and it doesn’t really work very well yet.
There are certain diseases with a very low hit rate – that is getting a suitable genetic modification to a very small number of cells is enough to be able to actually cure the disease. But in most cases you have to hit quite a lot of cells and we really just don’t know how to do that yet. We at SENS foundation are very interested in helping to address that problem and there is one particular approach to improving very substantially the ability to very safely introduce new DNA into a lot of cells into the body which we are just starting a project to explore. **

* Note this interview was done shortly before CRISPR was discovered.
** This project is called?? Note I will follow up with Aubrey de Grey on this point – but my feeling is that CRISPR may have solved the problem, at least partially

Adeno-Associated Virus

Adeno-associated_virus_serotype_AAV2One of the biggest dangers in somatic gene therapy and also it’s a danger for ex-vivo gene therapy (where you genetically modify stem cells and then you introduce them) is that on occasion the engineered gene may go into the genome in the wrong place – into a place that causes damage in the form of disrupting the DNA that was already there – in a way that you don’t want.  In general that disruption is harmless, but very occasionally it may not be harmless – it may actually make the cell cancerous (and there have been genuine cases of this in clinical trials for particular gene therapies).  So, people are very interested in ways to stop that from happening.  The most obvious way to stop that from happening is to develop a gene therapy vector (a type of virus) that preferentially goes into a particular harmless place in the genome and not go into any of the potentially harmful places – now it turns out that there are some viruses that naturally do this – there is something called AAV (Adeno-Associated Virus) which preferentially go into one particular site of chromosome 19 and people have been very interested in that virus for quite a long time for exactly that reason.  However it turns out that its quite complicated to make that really work and the hit-rate is not good enough – it still has random integration at an unacceptably high level.   So people will want to find other ways to go about this – and there really are lot’s of very creative technologies out there that are being explored to do exactly that.  I’m very optimistic that quite soon we will have gene therapy that very robustly does not disrupt DNA that it would be dangerous to disrupt.

RNA Interference

I believe there are other types of manipulation of gene expression other than gene therapy are also potentially valuable in treatment of ageing and of course medicine in general.  A lot of interest these days is in RNA Interference (RNAi) which is a method for inhibiting expression of particular proteins by introducing short RNA molecules that interfere with that process.  And that’s got a lot of potential – people are looking into it in a variety of different applications – one area that people have been trying to look into it for is cancer.  So see if one can close down cells that are over -expressing when they shouldn’t be over-expressing (for example).  Personally I’m not very optimistic about this application for cancer because it’s just too easy for cancers to mutate into a form that makes the RNAi in-effective – so the short RNA does not work anymore.  But in other applications it might be useful.

Neuro-Regeneration

So the brain is of course arguably the most essential to repair from the damage of ageing – there’s not much point in rebuilding the rest of the body if you are demented – how hard is that?  In particular is it significantly harder (to repair) than the rest of the body?  I believe it’s not significantly harder than the rest of the body – ultimately the brain is certainly vastly more complicated than any other organ, and we are vastly more ignorant about how it works than we are about any other organ – but the thing about SENS, the thing about the whole preventative maintenance approach to combating ageing is that we don’t need to understand how the organ works in order to restore its function or we need to do is understand what its made of, and more specifically how what it’s made of changes throughout life so that we can reverse these changes – repair those changes – and put structure and composition of the organ back to how it was at an earlier stage in early adulthood and thereby restore its function irrespective of our ignorance of how that function arises from that structure – that’s just as true for the brain and any other organ.  So one example of this is the fact that brain cells (neurons) don’t divide, and in most cases don’t have per-cursor cells that don’t divide either – there are a couple of areas of the brain that do exhibit the creation of new neurons throughout adulthood – the rest of the brain doesn’t luckily the rest of the brain exhibits a very very very slow rate of cell death – so it’s not really a problem – and the problems we need to fix are the problems of accumulation of garbage inside neurons for example, or outside of neurons that make those neurons not work so well even while those neurons are still alive.

 

Aubrey-de-Grey---SNES-Therapy-Delivery


Aubrey de Grey is the chief science officer of the SENS Research Foundation, which is a 501(c)(3) public charity that is transforming the way the world researches and treats age-related disease.

The research SENS funds at universities around the world and at SENS own Research Center uses regenerative medicine to repair the damage underlying the diseases of aging. The goal of SENS is to help build the industry that will cure these diseases.


Aubrey de Grey was interviewed by Adam Ford in 2012.

Here is a playlist of all the interview sections: