Aubrey de Grey of the SENS Research Foundation is an advocate and scientist focused on advancing the state of rejuvenation research, progress towards therapies capable of repairing the cell and tissue damage that causes degenerative aging. He put forward the Strategies for Engineered Negligible Senescence (SENS) research proposals some fifteen years ago, and since then has raised funding, organized research programs, cofounded the Methuselah Foundation and SENS Research Foundation, and traveled the world to speak at scientific conferences and meetings of supporters.
Back when this all began, members of the scientific community were very reluctant to speak openly about treating aging as a medical condition, the press treated the prospect of therapies for aging as a joke, and the public at large gave no attention to the topic. Yet the potential was there, with many disparate branches of research into age-related diseases demonstrating even then that scientists understood more than enough to get started on meaningful therapies to repair the damage of aging. The problem has always been cultural: that no-one cares, that funding is non-existent, that few are willing to step up and speak out on the issue, that the status quo of suffering and disease is accepted. With the help of people like de Grey and his allies the last decade has seen a real sea change in the research community and the media, however, as well as in the actuarial and the futurist communities, and the years ahead will see that change in attitudes spread to the population at large. If we keep working at this by the mid 2020s I expect the average individual in the street to think of aging in the same way as he or she thinks of cancer today: a fearsome medical condition that causes great suffering, researchers need to work harder at fixing it, and charities raising funds for research are a worthy cause.
Over at the Reddit /r/futurology community today de Grey was answering questions in an AMA (Ask Me Anything) event. It is worth remembering that every Reddit community of any size is a collection of widely divergent interests. Thus /r/futurology is a mix of folk who follow progress in computing technology, basic income advocates, popular science buffs, futurists of all stripes, both for and against longevity enhancement, and various other less categorizable groups. So the forum can host a respectful AMA for de Grey packed by people who look forward to progress in rejuvenation research just a day after a long discussion on a recent aging research paper in which most of those involved were opposed to human life extension. It is a big world, communication is making it smaller, and we're all rubbing shoulders these days.
Buck-Nasty: I'm curious about how the advent of CRISPR affects the development of SENS therapies?
Aubrey de Grey: It's huge. It will be central to the delivery of the many SENS components that involve somatic gene therapy.
Buck-Nasty: Does it speed up the development timeline at all?
Aubrey de Grey: A lot, yes.
Jay27: Kind of a shame, because it looks to me like deep learning algorithms will be plowing their way through a million genomes in 2020. You'd think they'd yield some valuable genemod insights which can then be applied with CRISPR.
Aubrey de Grey: We don't need insights right now - we need implementation of what we already know or are developing. That's why CRISPR is so important.
Senf71: Is it fair for me to be telling my friends and others I tell about this stuff, that considering the $25 a month I donate to SENS and the many dozens of people I have educated about SENS and curing aging in general, many quiet successfully educated, that I may have personally saved the lives of 100,000 people at this point? Along that line is this something it would be good for you and your people to really emphasize during talks? To tell people that they can feel good about them selves for going out and advocating and donating even a meager amount of money because doing so means they are very truthfully saving the lives or 10s or 100s of thousands of people?
Aubrey de Grey: This is by far the best question yet on this AMA. Thank you! First: I think you can say something like that (depending on how long it's been that you've been sending us $25). I believe that $1 billion right now would hasten the achievement of LEV by about 10 years; you can do the rest of the maths, but it comes out to about $2 per life - and of course "saving" means a great deal more in terms of extra years than it does for other ways of saving lives, so arguably it's more like a few cents per life. And yes, I think I should emphasise this more. I probably will.
Spats_Mgee: Several aspects of your SENS proposal are essentially destructive in nature (removing intra/extracellular junk, killing errant cells, etc). Your proposal to deal with these problems involves utilizing enzymes found in other species to break down these molecular structures. I'm curious if you've weighed the pros and cons of this (let's say "organic") approach to the "inorganic" approach of using gold nanoparticles for targeted photothermal ablation of these cellular/molecular structures.
Aubrey de Grey: We've looked at this approach and we haven't rejected it out of hand. A big issue is penetration: how does one irradiate deep within the body?
Lavio00: I watched a video from you back in 2013 where you commented the announcement from Larry Page about Calico. You mentioned that Calico - if they're focused on early stage research - might highly benefit the battle against aging. What is your comment regarding Calico's research now that a couple of years have passed? More/less excited about their potential?
Aubrey de Grey: Cautious. They are structured perfectly: they are doing a bunch of highly lucrative irrelevant short-term stuff that lets them get on with unlucrative critical long-term stuff without distraction. But the latter may be getting too curiosity-driven and insufficiently translational. We'll see. Here "highly lucrative irrelevant stuff" = drugs for specific diseases of aging, "unlucrative critical stuff" = work leading to actual longevity escape velocity.
SirT6: One thing that has always struck me about your vision for extending human lifespan is that you don't seem particularly interested in attempting to leverage the molecular genetics of aging. Numerous animal studies have implicated a number of genes which may serve as pharmacological targets for ameliorating aging and age-related pathologies. Studies of human centenarians have also validated the idea that modulation of these genes or their protein products may be a viable option for extending lifespan. And from an evolutionary perspective, this seems to make sense - many genes exhibit antagonistic pleiotropy (good when young, bad when old), so inhibiting these genes/proteins as people age is likely to reduce the burden of age-related disease. I suppose you could argue that this won't drastically increase human lifespan, but it seems to be a far more tractable approach in the near term (clear molecular targets, easier biomarkers, simplified drug development etc.). I would be curious to hear your thoughts on the issue. Thanks!
Aubrey de Grey: You put your finger on it - tractability versus magnitude of effect. As I think you know, I subscribe to the school of thought that CR-mimicking genetic or pharmacological manipulations cannot to much in long-lived species. I don't want to suppress such research, but I do think that the field has been immensely harmed over the past 20 years by overoptimism concerning the CR-mimicking approach and consequent lack of interest in alternatives. Antagonistic pleiotropy has very little to do with this.
akerenyi: I believe that the distinction you make between SENS-type of research focusing on damage from ageing and research on age-related diseases (ARDs) is purely arbitrary and misleading. For example you correctly claim that ageing and ARDs are pretty much the same thing, but than go on the criticize research on ARDs for not focusing on the right thing, while even further you plan to use therapeutics coming from this research, like Alzheimer's vaccines for rejuvenation (correctly so). I think the reality is that research on ARDs does involve more basic, mechanistic work as well as more later-stage, symptomatic approaches, compared to your engineering approach. However, I think the former gave and will give the targets for SENS, like beta-amyloid or tau, while the latter gave us drugs like levadopa, which while being crude and non-definitive, did improve the quality of life of millions of patients, while stem-cell therapy or gene therapy is being developed. Please clarify whether you still think such a distinction is desirable or meaningful.
Aubrey de Grey: The issue is relative funding. Illustration: it is absolutely accepted that atherosclerosis, the #1 killer in the western world, starts with the inactivation of macrophage lysosomes by oxidised cholesterol. Yet, about two labs in the world are focused on that step. I'm very satisfied indeed with the amyloid-beta vaccine results - they eliminate plaques. Same with gene therapy.
jimofoz: Can you give us any updates on the research towards allotopically expressing all 13 protein coding mitochondrial DNA genes?
Aubrey de Grey: It's going really well. We've made big breakthroughs this year and we'll be publishing something soon.
jimofoz: How pleased are you that Gensight is now taking the allotopic mtDNA expression technology whose development SENS partially funded into stage III clinical trials?
Aubrey de Grey: Overjoyed. We funded the Corral-Debrinski lab early on. Our work is leaning heavily on their early discoveries.
Aubrey de Grey: It's tough as hell but yes, we are plugging away. Watch this space.