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A Look Back at the Science of Longevity and Advocacy for Rejuvenation in 2017

Another year is over, and we're all that much closer to both the ugly declines of aging and the advent of rejuvenation therapies. For those fortunate enough to be in a younger demographic, which of those two items wins out depends entirely on the pace of progress. We are in a race. The results matter greatly. Every effort made to help will shift the odds to be that much better.

A Year of Ups and Downs in Fundraising

Insofar as fundraising goes, this has been a mixed, interesting year of ups and downs. On the one hand it has been a struggle to raise funding for smaller non-profit projects, such as the MouseAge and AgeMeter initiatives at Lifespan.io. At the same time companies working on rejuvenation biotechnology have obtained angel and venture investments, and new venture funds are entering the longevity science community. Ichor Therapeutics announced a series A for their SENS-based Lysoclear technology, and later in the year their other spin-off Antoxerene was funded. Oisin Biotechnologies expanded their technology to target cancerous as well as senescent cells, and are also raising more funding. Other companies involved in senescent cell clearance have done well; SIWA Therapeutics pulled in new funding for their antibody approach, for example, and CellAge was seed funded to work on better assays for senescence. Unity Biotechnology continues to have enough of a war chest to buy the rest of the nascent industry should they so choose. AgeX Therapeutics launched, with Aubrey de Grey on their staff - that should be interesting. LIfT Biosciences seems to be doing well in their efforts to bring leukocyte transfer therapies for cancer to the clinic.

On the other side of the fundraising fence, the Methuselah Fund launched this year, taking a mixed non-profit/for-profit approach, and from the funds raised from our community invested in Leucadia Therapeutics, supporting a new approach to clearing aggregates that cause neurodegeneration. Larger monied interests arrived in the form of Jim Mellon's Juvenescence venture, who have initially invested in Insilico Medicine, but have indicated support for the SENS research agenda. As this is a vocal group, we can expect to see them influencing public and investor opinion rejuvenation research and development in the years ahead.

Despite all of the challenges faced by non-profit fundraisers over the course of much of 2017, the year ended on a high point: the SENS Research Foundation year end fundraiser pulled in $1 million more than the target of $325,000 or so in pledges, as the anonymous principal of the Pineapple Fund donated $1 million in bitcoins in December. The Fight Aging! SENS Patron component of that year-end fundraiser came to a successful conclusion: Josh Triplett, Christophe and Dominique Cornuejols, and Fight Aging! put up a $36,000 challenge fund to match the next year of monthly donations, and that target was reached. Many thanks are due to all who supported SENS rejuvenation research over the course of the year: this funding makes a real difference, especially now that multiple lines of research are closing on the point at which commercial development can begin. You might take a look at the SENS Research Foundation annual reports and the state of progress in SENS addition to the Fight Aging! FAQ for a sense of how things are going.

Finally, with all of the hype surrounding blockchain initiatives this past year, it was inevitable that some of the adventurous souls in our community would make the effort to run initial coin offerings and see whether or not this was a viable path to pull in funding. The Open Longevity organization set out to give it a try, and so did Youthereum. It is a little early to say where this will all go; it is a very rapidly changing area of effort.

Expanding Efforts in Advocacy

Discussion of advocacy for the cause is a usual feature of our community, as we try things and attempt to make progress in persuading the world that rejuvenation research is plausible, practical, and necessary. There are more people engaged in advocacy now than at any time in the past decade, and so discussions of strategy come up often. New ventures kicked off in 2017 include the Geroscience online magazine, and among the existing ventures the LEAF / Lifespan.io volunteers seem to be hitting their stride. The mainstream media continues to be as much a hindrance as a help, and where it is a help you will usually find Aubrey de Grey involved in the article somewhere - which is not to mention the recent /r/futurology AMA.

In the broader question of strategy in advocacy, questions abound. Do we continue to spend a lot of time tearing down arguments against treating aging as a medical condition, such as the naturalistic fallacy and unfounded fears of overpopulation? Should we be avoiding talk of immortality and radical life extension? Or focusing on ethical arguments? Or correcting mistaken views of aging and the underlying biology? Trying harder to persuade people that rejuvenation therapies are a near future possibility? Or trying to address some of the unhelpful behavior from some members of the research community? Or continuing to hammer on the costs of failing to address aging, the worldwide toll of death and suffering? Or continue to hammer on the benefits of success? Do we talk less and strive to engage with structural problems in the funding of research? Or endeavor to find more funding for advocacy rather than sending it all to research? Given the fact that we have to keep making the same arguments for incremental gains, are we bad at this advocacy business, or is it a tough challenge? Should we switch some of this non-profit activity to for-profit activity?

We must keep making the case, of course - the benefits of success are enormous. There were some sizable wins in advocacy this year, such as a series of YouTube videos from popular channels that covered the prospects for the treatment of aging and were viewed by hundreds of thousands of people.

Topics in Longevity Science from the Past Year

Is genetics important in longevity? Some researchers think that most of the observed variation in human life span is chance, not genes. There has been plenty of other research this year on human genetics that are related to longevity, and there are a number of large commercial ventures working in the space, but it is going to be hard to top the discovery of human PAI-1 mutants who appear to enjoy a seven year gain in life expectancy. Since this mutation is closely connected to cellular senescence, it seems plausible that we should read this as support for the benefits of senolytic therapies. A similar discovery was made for a growth hormone variant, with a much smaller effect, of course. That aside, analysis of genetics doesn't look like a fast road to sizable results for a variety of good reasons.

Cellular senescence research continues apace, of course, alongside the commercial efforts to bring senolytic therapies to the clinic. The research community has now well and truly woken up on this topic, and many researchers are increasingly optimistic that senolytic treatments will be transformative for medicine. New work now implicates cellular senescence in kidney disease, macular degeneration, osteoarthritis, cardiac hypertrophy, sarcopenia, lung diseases, vascular calcification, immune system aging, fibrotic diseases, fatty liver disease, skin aging, declining regenerative capacity, the accelerated aging effect of chemotherapy, the effects of visceral fat on health, and more.

Some groups are trying to find ways to reverse senescence, sabotage harmful signaling by senescent cells, or prevent cells from entering this state - though it is unclear as to whether or not these classes of approach will be significantly helpful, given that the cells are damaged. The more direct and definitively effective approach of destroying senescent cells continues to gather more potential methods. This past year, the very intriguing method involving FOXO4-DRI was demonstrated in mice - we can hope it holds up in human studies, as this looks considerably better than the current crop of repurposed chemotherapeutic senolytic pharmaceuticals. Those chemotherapeutics expanded to include HSP90 inhibitors quite recently. Meanwhile exploration continues in search of better ways to assess the number of senescent cells in tissues; current approaches just aren't all that useful for human clinical applications.

Beyond clearance of senescent cells, other lines of SENS research are progressing. This year, glucospane research turned to the creation of monoclonal antibodies to aid in building a therapy to break cross-links in aged tissues. Gensight continues to find success in their implementation of allotopic expression of mitochondrial genes, proving out the technology platform that will ultimately become a rejuvenation therapy.

Given the advanced state of senolytics, it is only natural that our community is starting to think about trials and how to run them - in addition to whatever the various companies in the space might put together over the next couple of years. Paid trials are a good idea, but there is an unaccountable amount of hostility towards them from the scientific community. Groups such as Betterhumans and the Society for the Rescue of Our Elders are running small, independent senolytic pilot studies. Responsible self-experimentation is another time-honored way forward. Some people are trying it for senolytic treatments. I have put some thought into the logistics and what tests one might use in order to determine whether or not a particular treatment is useful.

Self-experimentation in the broader community nowadays extends to comparatively crude gene therapies, with a number of organizations offering the tools or running the trials. These technologies are too cheap and too easily used to be more than inconvenienced by regulators. A few companies are headed in the same direction, such as Libella Gene Therapeutics, with a plan for human telomerase gene therapy trials, following in BioViva's footsteps.

Lines of research emerging from parabiosis studies, in which old and young individuals have their circulatory systems linked, continue to expand. The core questions regarding whether beneficial factors in young blood or harmful factors in old blood are responsible for the observed effects on aging, or both and to what degree, continue to be debated. While the weight of evidence leans towards "bad old blood" with a few specific candiates for the factors causing that effect, it is still the case that new studies with evidence for beneficial factors in young blood continue to arrive. The contradictions will eventually be resolved, but for now it is an area of research in flux. Meanwhile, human trials of plasma transfusion from young to old continue; Ambrosia and Alkahest reported results that are ambiguous enough to resolve nothing.

Cryonics remains an important and underappreciated technology. Not all of us are going to make it; the progression of rejuvenation technology won't happen fast enough. We will need the backup plan of cryonics. This year marks the fiftieth anniversary of the first, comparatively crude cryopreservation, and that individual, unlike most of those from of that era, remains preserved. The technologies of preservation today are far more advanced, and the organizations more reliable in the face of various failure modes, as noted in an interview from earlier in the year. One line of work that has made considerable progress of late is safe and rapid thawing of vitrified tissues. In community news, the International Longevity and Cryopreservation Summit took place in Spain earlier this year.

Is Google's large investment in aging research, the California Life Company, Calico, at all relevant to the goal of defeating aging? The more we find out, the less likely it appears. Researchers are increasingly willing to go on record as saying that the efforts funded there are just not helpful in the near term. Calico looks like pure curiosity-driven scientific research into understanding the very fine details of aging, which is not what we need at this stage in order to push forward to the range of effective therapies that can be built in the near future.

Amyloid accumulation is one of the causes of aging, and transthyretin amyloid is one of the types of amyloid with more research interest. It is connected to heart disease and osteoarthritis, and may be the majority cause of death in supercentenarians. Covalent Bioscience is one of the companies looking at ways to remove this amyloid. A variety of new research was published this past year, including a better approach to assessing the amount of amyloid present, and RNA inteference and antibody based therapies.

On the topic of biomarkers of aging, there are many various lines of work taking shape. The research community agrees that having effective, reliable biomarkers for a rapid assessment of biological age is very necessary to speed up progress towards treatments for aging. Among efforts noted this year include gene expression of glia, metrics based on neuroimaging, or on microRNA expression, various attempts to assemble a compound biomarker from a collection of standard lab tests and measures. People are setting up online databases to hold the various prospects. DNA methylation tests based on one or more of the existing epigenetic clocks have now reached the consumer marketplace. They can be ordered from Osiris Green and Zymo Research. The research community continues to refine and expand further epigenetic clocks and related assessments.

Calorie restriction is ever a popular research topic, despite this being unlikely to produce very large effects on human lifespan. This is really the core of the geroscience view of the treatment of aging: slow it down a bit, but don't try for more. Researchers now claim that human studies show a slowing of aging via a collection of biomarkers. The final consensus on long-running primate studies appears to be that, yes, calorie restriction does modestly slow aging in our near relatives. Near all specific measures of aging are similarly slowed, such as the fibrosis leading to kidney disease, the early stages of cancer, the epigenetic changes of aging, the decline of the immune system, the accumulation of metabolic waste in cells, and the accumulation of amyloid in aged tissues. Researchers continue to find new mechanisms by which calorie restriction produces its effects, such as a slowing of ribosomal activity. Sense of smell continues to surprise the research community in the degree to which it is important in determining response to calorie intake. A number of researchers have gained traction in pushing forward intermittent fasting as an alternative approach, particularly the fasting mimicking diet. Meanwhile, ever more candidate drugs and protein targets are found that might act as a basis for potential calorie restriction mimetic therapies - though given the lack of concrete progress on this front over the past decade, I wouldn't hold my breath waiting for results.

Another rising topic in aging research is the contribution of gut microbes and other microbial populations in the body; these may be as influential over aging as, say, exercise or calorie intake. Researchers have noted influences on amyloid accumulation, something that is attracing greater interest from the Alzheimer's research community. It is also interesting to see studies demonstrating extended life as a result of transplantion of gut bacteria from young animals to old animals in zebrafish and in mice, or showing that healthier older individuals have microbial populations more like those of younger individuals. Moving beyond observations, candidate mechanisms are being discovered to explain exactly why changes in gut bacteria are good or bad. The next step is therapies that target those mechanisms. Researchers appear close to being able to sabotage the detrimental effects of oral bacteria, for example.

A few interesting views on aging and its origins surfaced in the past year: aging as a consequence of complexity in cellular life, for example, or that aging is an inevitable consequence of competition between cell types in multicellular life. Another group argued for selection to decline with age even in hypothetical immortals, thus ensuring that no species would become so exceptionally long lived. Others have looked for explanations for the present state of stem cell populations, in that they are not as effective as they could be, especially in later life.

Work on addressing dysfunction in the immune system by destroying near all immune cells and then repopulating them via cell therapy, shown to cure severe autoimmune disease is progressing on a number of fronts. The most important thing here is to find a safer, less damaging way to kill the unwanted parts of the immune system. Currently it is too risky to be applied to older people, so as to clear out the issues in an aged immune system. Researchers recently discovered a promising lead here.

Regenerative medicine, cell therapies, and tissue engineering are energetic fields. Far too much is going on to note all of it, but a few things caught my eye. The Methuselah Foundation continues to be in the thick of it with their initiatives to promote progress, for example. Decellularization continues to be an important line of research, and that will be the case until someone figures out a reliable means of producing blood vessel networks. Bioprinting of tissue proceeds apace, and is driving a lot of the advances in reduced cost and increased capabilities. Researchers are building ever more and better organoids: fully functional ovaries, stomach, skin that is fully and completely structured, lungs, thymus, bile ducts, inner ear, and more. Organoid production is on the verge of scaling up, and use of multiple organoids may work well as an alternative to full organ transplant for some organs. In other parts of the tissue engineering field, mass production is also an ongoing interest. Organ factories are not so very far ahead. Teeth are similarly moving forward; tooth regrowth has moved up from rodents to canines. Researchers are also making inroads into the manufacture of blood to order.

Will regenerative medicine make the leap soon from cell therapies that do little but suppress inflammation, to actual methods of rejuvenation and repair? That is hard to say, and the final form of such therapies is also uncertain. Consider induced cell turnover or artificially increased cell replication strategies for example, a novel approach where the implications have yet to be fully explored, or the variety of cell therapies that appear to produce quite sizable changes despite using only incremental advances in methodology, or very novel processes such as reprogramming skin cells into stem cells in a living individual. Comparative biology continues to deliver intriguing findings from lizards, spiny mice, zebrafish, and the like. Related work is finding that adjusting the balance between populations of macrophages with different polarizations can spur greater regeneration in mammals, and the same may be true of microglia.

2017 Short Essays

You'll find a number of short essays at Fight Aging! each year. Here is a selection from 2017:

Looking Ahead to 2018

Next year should see the first published results from senolytic trials - and if the effects of the first drug candidates translate well from mice to humans, that should wake up everyone not yet aware of the enormous potential of this field. I expect that this will probably overshadow everything else achieved in the field for a while, at least in the public eye. There will be more startup companies launched to work on SENS rejuvenation biotechnologies, and that will hopefully be an ongoing story for the next few years. This period of transition, handing off from laboratory to clinical development, is critical to the future of human rejuvenation therapies. The more we can do to help, the better.

Comments

Thanks Reason for the effort of putting up a summary of the year!

Posted by: Antonio at December 29th, 2017 3:54 PM

Thanks for the great summary Reason. We are definitely starting to gain ground on the advocacy side.

We have also prepared a year in review at LEAF should people wish to see our summary of the years events.

https://www.leafscience.org/2017-review/

Posted by: Steve Hill at December 29th, 2017 4:12 PM

@Reason, thank you very much for you amazing review!

Posted by: Ariel at December 29th, 2017 4:24 PM

Great summary Reason!

Overall, this has been a very good year. I think we have reached a tipping point and things will snowball from here. Lets hope 2018 goes exponential for us.

Posted by: Mark Borbely at December 29th, 2017 5:41 PM

I think progress in 2018 will be enormous.

Posted by: Norse at December 30th, 2017 12:50 AM

Happy new year!

Posted by: Gekki at December 30th, 2017 12:51 AM

This was really pleasant to read. There's so much going on in the field of longevity now and it seems that 2018 will become even better. With CAR-T hitting the market and stem cell treatments following soon we'll hopefully see the start of a significant upwards trend in life expectancy. A happy new year to everybody.

Posted by: Matthias F at December 30th, 2017 3:33 AM

I want to greatly thank Reason for all of his time in (very) consistently doing this blog, 3 times per day, 5 days a week, 52 week per year. You are greatly appreciative for providing the latest info in the longevity news and my main go to source for this. So, thank you Reason, for your efforts over the many years of this. I hope you have a great and prosperous new year. And, yes, I with you and all readers of this blog in hoping very much that the momentum continues in the field of longevity.

Also, I think once we can get aged tissues into clinical studies for cosmetic purposes and of course the senolytics on line, it will speed up the rejuv greatly.

As it is my birthday tomorrow, Dec 31, it is not pleasant to see another year for me so I greatly look forward to some serious advances available to the general public.

Happy New year all.

Robert

Posted by: Robert at December 30th, 2017 1:35 PM

"As it is my birthday tomorrow, Dec 31, it is not pleasant to see another year for me"

Surely less unpleasant than the alternative Robert :)

Posted by: John S. at December 30th, 2017 11:18 PM

I think a real tipping point with public support/interest might occur if a therapy in trial results in cosmetic improvements in the participants appearance. I don't think Unity's planned trial of injecting senolytic drugs into arthritic knees will achieve this.

Maybe some combination of systemic treatments targeting 2 or 3 types of SENS damage would achieve an improvement in people's appearances? Once that happens it is game over for the opponents of Rejuvenation Biotechnology research.

This is probably the situation in which overseas clinics such as BioViva could provide the most value. If people start going to a Caribbean clinic, get most of their senescent cells and glucosepane removed, and perhaps some amyloids and intra cellular garbage, and look 10-20 years younger, this would be a shock for most of the public.

Posted by: Jim at December 31st, 2017 12:33 AM

@ Jim : I guess cosmetic changes would wow the public, but sceptic scientists might not be moved until RMR happens. Anyway, just getting the general public onboard would be enough.

Posted by: Spede at December 31st, 2017 7:27 AM

I just got a WOW surprise last night, when I checked my SERPINE1 gene SNP rs1799768 -/G (null and G alleles) for the PAI1 protein mutation mentioned by Reason as the most exciting genetics advance in knowledge for life extension this past year. Well, I was shocked to find that I have the null allele for the SERPINE1 gene that results in the PAI1 SNP mutation. According to Reason, this yields a 7 year increase in lifespan, although some of the research and media articles mention a 10 year life extension. At any rate, it is difficult to find these rare longevity SNP's, which is why we don't know all the genetic factors that go into long life.

Posted by: Biotechy at December 31st, 2017 9:00 AM

The PAI1 protein expression normally results in increased scenescence in cells and tissues in aging, but the null mutation for the longevity SNP significantly inhibits PAI1 protein expression in cell and tissue with aging. The telomeres are 10% longer in those who have the mutation, insulin levels are lower and there are a number of other beneficial metabolic factors as well. This is predominantly a scenescence reducing mutation. Thus, you would think scientists could knock out the bad PAI1 aging allele so that people could live 7-10 years longer. Or perhaps CRISPR technology could be utilized to accomplish the task.

Posted by: Biotechy at December 31st, 2017 9:39 AM

@Jim

Personally I think the obvious impact upon sport might be enough to produce a tipping point, and that will likely happen before we see celebs looking 20 years younger. If Federer is still winning Wimbledon at 40 and if it was widely known he had received a senolytic treatment, then you can be sure every 40+ person would be getting excited by this.

How do we know that top sportsmen in their 30's aren't already self-experimenting? It does seem a little odd that in the last couple of years we have had some remarkable feats of sporting longevity - Tom Brady, still a top NFL player at 40; Roger Federer winning Australian Open and Wimbledon at 35; Klitschko narrowly losing a world heavyweight title bout at 41 to a guy nearly two decades younger tipped to be an all time great; Justin Gatlin winning 100m world title defeating Usain Bolt at age 35 - an event that consist of raw athletic speed which should decline from the mid twenties.

Posted by: FutureTechInvesting at December 31st, 2017 11:52 AM

@FutureTechInvesting: I agree with you. There is already plastic surgery to make people look younger, so even if someone comes back from their Thai vacation looking like they shaved off 10 years, how is anyone going to differentiate true rejuvenation from a good nip & tuck? Your telling them that you are younger after senescent cell removal is not going to be more convincing than your telling them that you are younger after getting a "stem cell face lift".

The tipping point will be either seriously reduced mortality rates in the very old (e.g. headlines screaming that incidence of cancer, cardiovascular disease, alzheimer's has been slashed in some group of over 80s) or performance. And of course the most public way of monitoring performance is through competitive sport. Having said that, a professional athlete's shelf life is already much longer than even just a couple of decades ago, and that's because of localised orthopedic interventions that do not prolong life.

So I suspect it will be our grandmas' new penchant for tennis and hikes that'll tip the scales. To convince the general public that rejuvenation is possible and in fact happening, we need new results rather than new ways of achieving what looks (even if it isn't) like the same old.

Posted by: Barbara T. at December 31st, 2017 12:33 PM

Thanks reason. Happy birthday Robert. Congrats Biotechy, if true. @FutureTech, we can be reasonably certain the pro sport examples you site do not have access to to some Elite longevity science because PEDs and sports science are 10x better understood and available than longevity science, not including mesenchymal (sp?) stem cells, which have a strong sport science application and may have some small longevity benefit.

Posted by: JohnD at December 31st, 2017 1:29 PM

Can't we use Crispr or some other method to give us, the people who are interested in living longer, the right alleles known to date that extend life...why concentrate only on the PAI-1 mutation? I would think then we will get synergistic effects and get more than those 7-10 years (although this is already a lot for one mutation). I'm thinking of constructing our genome in a way so that it makes us age slower/live longer.

Posted by: K. at December 31st, 2017 2:07 PM

@Barbara - just my honest opinion, but plastic surgery doesn't really make anyone look younger, it just makes them look weirder. Hopefully rejuvenation biotechnology will come along in the next decades that can do better.

@FutureTechInvesting - good point that the people with the most incentive to embrace this are those in industries that value youth such as sports or acting. I don't think these people are aware of rejuvenation biotechnology in a serious way yet though. And even if they were aware, they would need an overseas clinic to buy the treatments from, and these do not exist yet, as the technology does not exist yet.

As long as even the current minimal financial support for rejuvenation biotech holds out, at some date in the future a tipping point will be reached. It is speculation as to whether this happens in the next decade, or decades in the future.

On a sobering note, as it is NYE I was talking to my friend about where we expect to be in 2030. I (gently) raised the possibility of life extension, but she was adamant that as it hasn't been done yet it is pie in the sky. I suspect a lot of the general public would react like her. So I hope visual improvements happen in the nearer term.

Posted by: Jim at December 31st, 2017 2:10 PM

@Reason: My Raw DNA data is from 23andme and the SNP I cite above has a lot of info from SNPedia under rs1799768 SNP discussion, if you would Google it you will find the Null mutation there with normal G allele. Now this SNP is very closely related to SNP number rs1799889 which may be the same SNP as I cited, but in any case, 23andme does not cite my Raw DNA data for it.

Posted by: Biotechy at December 31st, 2017 2:51 PM

Jim,

In regards to your 2030 comment... at that point, if there is something that can be used and has noticeable results, it's likely that only a small fraction of a percent of people would have made use of it. I don't say this because of an "only the rich" mindset, but because it most likely wouldn't be in clinics in the US, or EU due to regulatory hurdles, so people would have to get it via medical tourism. Also because we have only a relatively small community that would probably know about it... not much of a sample size for the general public to notice or buy into. And yes, I expect most of the general public to react like your friend as well, though from your comment at least it seems like the idea didn't offend her like it does so many others.

Posted by: Ham at December 31st, 2017 3:05 PM

thanks reason for this great highlight of the year. i hope 2018 is better, and we can engage with more people and increase public support. its anxious being 30 knowing this could not happen in time for us alive today, but i am very optomistic. aubrey seems more posotive too so ill go with his attitude.

happy new year everyone

Posted by: scott emptage at December 31st, 2017 3:35 PM

@Jim I agree with you on the choice of OA as a poor translational choice for a senolytic.

Companies have been chasing the holy grail of disease-modifying osteoarthritis drugs (DMOADs) for decades.

If a senolytic turns out to be just a fancy anti-inflammatory agent without inhibiting (or better yet reversing) structural deterioration, it will be a tough sell in a very crowded market

Per a recent FB discussion on the topic, if I was running SENS I would put 100% of my resources into proving only one intervention - the "roto-rooter" extracellular crosslinks for arteriosclerosis - this has been a holy grail that pharma has been seeking (and failing at) for years and even early proof-of-concept would generate billions of $$ in upfront licensing payments and the rest of SENS could be funded off of it - it also is a more "immediate gratification" indication and doesn't come with as much of the upstream metabolic connections as the other interventions do

I would not be spending a penny today on things where the translation is far in the future (OncoSENS / MitoSENS / LysoSENS) or where others have had poor to mediocre translation success to date (AmyloSENS and RepleniSENS)

Posted by: Ira S. Pastor at December 31st, 2017 4:46 PM

@Ira S. Pastor: Anyone willing to donate high six figure sums can effectively run SENS. Make a conditional donation and tell them which of the SENS programs to run with it.

Posted by: Reason at December 31st, 2017 5:27 PM

The public will never get involved. If it will take some sort of visible rejuvenation to be demonstrated in humans to get the public to do something, that would mean that plenty of funding was ALREADY available to develop those rejuvenation treatments. Once those treatments are demonstrated to work in mice, the biotech/pharma sector would pay an arm and a leg for them, and this would fund all of the rest of SENS without any public involvement.

Posted by: Florin Clapa at December 31st, 2017 7:20 PM

- "but sceptic scientists might not be moved until RMR happens".
isn't that the issue with all these "in mice studies"?

yet, seems like sens do not understand that and they bet that a "special mouse" will be "convincing".
we are looking for studies in people (or other large mammals)

- "I would not be spending a penny today on things where the translation is far in the
future (OncoSENS / MitoSENS / LysoSENS) or where others have had poor to mediocre translation
success to date (AmyloSENS and RepleniSENS)"

sens are stuck with their strategy and will just try to 'fit" anything inside their understanding, if something doesn't work as in their book (mitosens has already issues, just look at what CohBar is doing vs. poor understanding by sens team:

"Research by CohBar founders and their academic collaborators has revealed that the mitochondrial genome has dozens of potential new genes that may encode peptides capable of influencing cellular activities by acting as messengers between cells. In models of diseases associated with aging, these peptides have shown disease-modifying metabolic, neuro-protective, cyto-protective and anti-inflammatory effects"

https://www.businesswire.com/news/home/20160411006230/en/CohBar-Announces-Preclinical-Proof-of-principle-Publication-SHLP-Mitochondrial-derived

... oncosens is another issue ... their poor understanding on telomeres/telomerase is not leading anywhere. they better look at data from real research and start learning.

- (removing) senescent cells, probably is the only one that has some good outcomes.
however, there are still things that sens ignores or doesn't understand.
on the other hand are groups that do real research in this field for longer that sens, and they are much more modest not trying to hijack this area.

just look at Prof. Valery Krizhanovsky and his team @ Weizmann Institute of Science:

https://www.weizmann.ac.il/mcb/valery/

- AmyloSENS is another example of poor understanding from sens team.
the problem with sens is they have no medical experience, they do a lot of
theoretical and white paper research and that leads to lot of false conclusions, that looks very good and attractive on paper.

- as long as sens is opposing any different approach just because differs from their limited understanding, they are not going to progress much. no offense, but for example they try to dispute Carlos Izpisua's work ... well, Izpisua's work dwarf what sens has done so far. so whatever michael rae is writing in his "question of the month" articles, science is not showing anything in his favor. sorry, science is science not a well written article.

Posted by: abc at December 31st, 2017 7:21 PM

"Once those treatments are demonstrated to work in mice, the biotech/pharma sector would pay an arm and a leg for them"

Sorry - this is just not true and not how the industry operates in 2018 (Happy New Year) - maybe back in the late 1980's, but this is not the case

You will get 3 things with such data:

- "Come over and give a presentation at our BD / licensing group at Pfizer / GSK / Roche, etc."
- "Thank you for your wonderful presentation."
- "Call us when you have proof-of-concept in humans."

It is true that there is only one place where the financial support will come from - the proof-of-human-principle stage deals you can strike with the 800-pound gorilla (big pharma) which is the only game in town that has the ability to spend $200+ billion a year on new translational R&D (for stuff they need to keep Wall Street happy - exciting human data that can grow their top line sooner and move their stock) - it will not come from government (they will never care) nor will it come from the advocacy community in large enough tranches

Hence, SENS needs to start thinking less like a conglonmerate, but more as a bare-bones drug development shop and try to get one across the clinical proof-of-concept goal line

Posted by: Ira S. Pastor at January 1st, 2018 5:13 AM

"The public will never get involved. If it will take some sort of visible rejuvenation to be demonstrated in humans to get the public to do something, that would mean that plenty of funding was ALREADY available to develop those rejuvenation treatments. Once those treatments are demonstrated to work in mice, the biotech/pharma sector would pay an arm and a leg for them, and this would fund all of the rest of SENS without any public involvement."

You could not be more wrong. The public is already getting increasingly involved. Our monthly patrons have grown rapidly, our traffic and the level of support we have from not only the core community but new audiences has been massive. We launched two more projects this year thanks to the interest of the public, many of our donations came from people new to the field brought to us via our videos on Kurz.

So yeah, I think you underestimate the value of public engagement.

Posted by: Steve Hill at January 1st, 2018 6:00 AM

Ira, don't you think you're being a bit too cynical? Unity raised over $100 million without any human trials.

Steve, the projects at Lifespan.io seem to have petered-out, and the SRF/FA fundraisers aren't doing any better. Lifespan.io's 2017 projects brought in less funding than the earlier projects and were not SENS-related either, and since 2015, its SENS-related projects raised $204k. $360k was donated for the SRF's/FA's 2016 winter fundraiser, while only $215k was raised this year (minus Pineapple Fund's $1 million donation). Maybe overall public donations for SENS have increased somewhat (LEAF plus SRF/FA fundraisers), but I haven't heard that donations have reached even $1 million per year, after more than a decade of advocacy. Sure, even small amounts are important for getting the research done to spinoff startups, but remember that SENS still needs about $50-100 million per year for a decade, and all of the evidence suggests that almost none of that is going to come from the public.

Posted by: Florin Clapa at January 1st, 2018 1:32 PM

Happy New year, just a 2 cent (I don't like doing the lick moderator (but it's your creation here and I'm just a visitor annoying your comment section) but great work Reason, this is the best aging blog, there are so few and in other languages there are none whatsoever (not with this level of work on them. I thought of doing one but it's just too much dedication in life now as such I congratulate your tiredless dedication. This may inspire someone else to do the same in other languages/outside US whom feel they have no voice because (they are not in US) and are too small to matter (enough); though I do think that more than a decade ago it was smaller and most everything starts small and (hopefully) grows))).

Just like SENS.

@Florin Clapa

Hi Florin, just a 2 cent,

I wish us millions of dollars will rain down (wishful thinking I know).
Perhaps, SENS' problem was that it was too lofty (in its goals, it's important to aim for the moon but sometimes we need to readjust/(re)assess things and realize we might have overshot; and we won't make it (not as far as wished). But there is good thing for aiming higher, at least, later you might not reach goal but advancement, most likely, will be a bit higher than if you had not aim 'that high/the moon' in the first place because at least 'you will be dancing among the stars (a little bit 'higher' stars) than if you had been to conservative and just tried (many did that and it did not go very far/failed right off the bat; motivation and belief is important; so is hard work and funds availability; but they are just some elements to the success sauce (like failing being the most important element; when you fail you learn and you can start over; become better, with that said - making magic out of thin air and no funds is quite hard; and why you may fail, again, and again; again again until you give up and put a nail in the coffin on it (that'S quite possible, let,S hope it will not be the case here)))).

If we need 75 million dollars (50-100M avg.), then we need to convey more rich people and bitcoins-holding doners. Or maybe we should mine for bitcoins ourselves (jk).

This goes back to main point, 'too lofty' goals by SENS, and now may not be 'Achievable' for lack of funds. If we needed 75 millions, it would take like 30-50 years to get all that cash by public/millionaires.

That is where I think, SENS could change approach, mid-way, and say, instead of trying to do All of this - which we know we can't - because we don'T have the cash for it.

We will focus on 1 or 2 specific things, just in the mean time, and show Proof of Concept to investors etc...such as some have said, rejuvenating a mouse with apoptoSENS senolytic therapy first - and Well. IT must work very well and be a Clear demonstration that they Back Their Words with Tangible Proof.

Later...they can get back to 'Working on the rest' of therapies - but at least, Now, the money will be flowing in and it will make them much more at 'ease'/easy to make the other therapies because without the funs SENS stalls and lingers; or fails utterly in a few years.

Money is the single largest problem here, we must 'smallify' this and show just 1 therapy working with complete assuranace and proof. Not try to make 7 therapies on a dime's worth.

Or even a 2 cents Worth.

it's not enough.

Just a 2 cent.

Posted by: CANanonymity at January 1st, 2018 2:40 PM

#Florin

No - Unity put together a rare, but impressive LS PE round for a pre-clincial company, no doubt, but that still is pennies compared to what they need to advance any single compound across the finish line with an indication

Big pharma wants late stage, human POC candidates to allow for the 10% topline growth they are promising Wall Street and to move their stocks

Posted by: Ira S. Pastor at January 1st, 2018 2:45 PM

Jim, great article, thanks much for your efforts.

My two cents on couple of topics:

- Advocacy: what would probably work best is what is, not incidentally, making progress right now. Start with well researched compounds that can slightly slow down aging and produce reduction in medical costs (metformin, rapamycin). Yes, I know this is not effective long term, and that we can do much more, but we have to start somewhere, and the therapies of this type would buy time for many people to live long enough to take advantage of more effective treatments later on. What we should popularize most is what majority of people can understand and relate to, not the ultimate goal (indefinite life extension).

- Calico: I think this venture is structured to produce results in the 20-40 years time frame - the time Google founders personally will need aging treatments. They didn't do it on purpose, it's that it always works like that with these tech guys: in their twenties, they write apps that tell you which bar you should hang out at; in their 30s, the apps that help you track your fertility cycle...

Posted by: Jamie_NYC at January 1st, 2018 4:34 PM

Well, it's no surprise that pharma is cautious, since nearly all of the stuff that's out there is garbage compared to SENS stuff like senolytics. And remember that the game isn't being played only by pharma but also by SENS-focused investors like Bezos who have infinite amounts of capital. So no, Unity is probably not a unicorn.

The focus-on-one-thing strategy as you (Ira and CANanonymity) suggested has been in the back of my mind for several years, but I've assumed that the SRF has thought of it too and probably has good reasons (I can think of several) to pursue the shotgun approach instead. Anyway, maybe I'll finally ask them about it.

Posted by: Florin Clapa at January 1st, 2018 10:13 PM

@Ira - the problem with picking winners is that no one is very good at it.

Posted by: Jim at January 1st, 2018 10:57 PM

@Jim

I agree - G_d knows this

But it is best to err on the side of translational success.

The pharma industry has spent the last 100+ years for the most part being "scientifically wrong" in regards to the targets of health and diseases, but "translationally right" as far as generating interventions that make clinicians / regulators / patients somewhat happier, while generating trillions of $$ of wealth.

I see a disturbing trend as of late, especially in the aging field (sorry to say), where the dynamic is changing, where we are getting scientifically "less-wrong" in regards to our targets, but becoming translationally "horribly wrong" in regard to our pharmaco-therapeutic thinking.

Posted by: Ira S. Pastor at January 2nd, 2018 5:48 AM

I think a chart of (estimated) private investment in SENS research would be useful if one could collect the data. I speculate that ~$100B/year will be necessary to create the necessary political/economic critical mass to ward of the enemies of SENS who profit from "treating" the diseases associated with aging, and the captured Government regulators. I think we are 3 to 5 years away from that threshold currently.

Posted by: Tom Schaefer at January 3rd, 2018 10:23 AM

@Reason: After looking into the SNP I cited above earlier this week, it turned out to be another but different Null mutation of the SERPINE1 gene. The mutation in the heterozygous condition also lowers the expression of the scenesence causing PAI-1 plasmingogen activator inhibitor about 50%. If you get too much inhibition as with the homozygous condition of the Null mutation, you get too much risk of bleeding.

Posted by: Biotechy at January 3rd, 2018 3:55 PM

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