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) – they 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? The first thing: Funding. The shortage of funding is still the biggest bottleneck. 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 – 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 – emphasise 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 immagrate into space – the people who are conerned 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 regerative 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 theroapy – no body wants alsimers, or heart disease – if the oucome of rejereative medicine is that then it’s easier to sell.
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, so 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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