Looking Back at 2013
Permalink | View Comments (11) | Post Comment | | Posted by Reason

Another year flees past us, ever faster it seems. The past year was characterized by advocacy, shifts in publicity and organizations supporting longevity science, and community fundraising success. For example, we just finished raising $60,000 for the SENS Research Foundation in the last few days. Back in October Longecity raised $21,000 for another SENS research project: restoring function in mitochondrial mutants, an opportunity to use a pair of cell lines that suddenly became available, and would otherwise require a great deal of work to produce. The month prior, a film project on life extension raised $35,000 on Kickstarter. Publicity is good, but I can't help feeling that we have a way to go yet with our advocacy when it is easier to raise funds to talk about longevity science in fiction than it is to raise funds to actually build the technologies needed for human rejuvenation. Ah, priorities. We humans are so bad at priorities.

Alongside all of this community fundraising, the new crowdfunding models are starting to make some inroads into science - moving beyond comics and games and widgets. I see this as a promising sign. Making community fundraising for projects like the ones above, and providing better tools to help the organizers, can only lead to more projects being funded and a growth in the number of supporters.

In a similar vein the Methuselah Foundation recently officially launched the New Organ Liver Prize: $1 million for the production of a tissue engineered, functional, transplanted liver. Their fundraising proceeds apace as they continue to work on speeding up whole organ tissue engineering through a variety of avenues.

While we are on the subject of Foundations, this was the year in which the SENS Research Foundation launched their Reimagine Aging campaign, added scientific luminary George Church to their advisory board, hosted the SENS6 conference, reached a yearly budget of $4 million, filled out their YouTube channel with videos, and posted an excellent series on the work done by young molecular biologists in their intern program. The SENS research program to watch in the coming couple of years is the AGE-breaker project focused on glucosepane, I think, but you really should take a look at their annual reports to get an idea as to how the Foundation is growing, and be sure to read The Undoing of Aging. You should also absolutely catch the Ben Best interview of Aubrey de Grey from August.

Interestingly, one other noteworthy group in aging research has published their own manifesto on how to treat degenerative aging, clearly modeled on the SENS proposals. That looks a lot like victory from where I stand.

The big funding news for the year in mainstream aging research is that the Ellison Medical Foundation is exiting the arena, and the vaguely aging-related Genomics X Prize was cancelled. Meanwhile Google has created the Calico initiative with the determination to spend hundred of millions of dollars on extending healthy life. At this point I don't expect Calico to back anything so useful and ambitious as SENS - I think it will look a lot more like a backing of the slow road to nowhere of metabolic manipulation to reduce the pace of aging. No rejuvenation research there. I may be wrong, but we shall see.

Various campaigns such as the Longevity Dividend have made new publicity efforts this past year to attract more public funding to their vision of incremental slow progress towards drugs to ameliorate the effects of aging. In addition we've seen other signs of the spread of awareness of longevity science into the mainstream: a radical life extension policy wonk conference, a big well-publicized study on views of radical life extension from Pew Research, and an advertising campaign touting 150 year life spans from Prudential. There is movement: each year we come closer to mass support for the goal of longer, healthier lives, yet still much of the public seems strangely disinterested.

Telomeres have been floating around in the news in relation to longevity this year. This is largely a consequence of new services offering telomere measurement, rather than anything of greater utility. Startup companies tend to generate press as a side-effect of their existence, but that doesn't necessarily tell us anything. On the more interesting side, the teams working on life extension in mice through telomerase gene engineering published new results earlier in the year. This is one of those items that gives me pause on my opinion of telomeres: other than this, it seems very clear from the data that telomere length is a marker, a consequence of aging and not a cause. I look forward to learning more about how telomerase in mice is actually extending life.

Mitochondrially targeted antioxidants of several types have been a topic of interest for some years now. To the extent that they extend life - where normal antioxidants do no such thing, or block hormesis signaling to shorten life - this is a reinforcement of the importance of mitochondria to aging and the need for mitochondrial repair technologies. A new type of mitochondrially targeted antioxidant known as SS-31 showed up publications earlier in the year, and makes for interesting reading.

This was the year in which research into brain emulation became more serious. Very large sums and formal programs are now working on creating first simulations and later emulations of the brain. Relevant to life extension? Not directly, unless you are one of those who believe that a copy of you is still you - but this bears watching. In a related community, the 2045 Initiative held their Global Futures conference back in June. This is another initiative that is worth keeping an eye on, though I don't believe it relevant to actual progress in extending human longevity despite their claims - and for much the same set of reasons as for brain emulation. A copy of you isn't you.

There are some puzzling oddities floating around the edge of the field of aging research, made puzzling simply by virtue of the fact that all too few people are studying them. The results arrive slowly and intermittently as a result. These are items that are likely irrelevant to the future of human life extension, but that doesn't stop them from being interesting. One of the best, I think, is whether and how heavy water extends life in short-lived species.

Immune therapies are one of the more active areas of medical development at the present time. Guiding the immune system has very broad applications: treatment of cancer, removal of amyloid and other waste compounds, and reversal of age-related immune dysfunction. Even something as simple as generating enormous numbers of patient-matched immune cells and infusing them can be very beneficial for the old, a way to restore some of the immune capacity that they now lack.

Several groups of researchers are at present chewing through past claims of life extension in mice from various dietary components and supplements and disproving them one by one. This seems to be the trend: look at every such claim from the past few decades with suspicion, as they likely resulted from inadvertent calorie restriction and are now being refuted by more careful work. The present consensus is that aggressive supplementation does nothing or may even be harmful to life expectancy.

In the area of drugs to slow aging, there is some debate over whether rapamycin actually does slow aging in mice versus just reducing cancer rates. This is ongoing with some fairly energetic arguments on both sides, especially from those already fairly vested in mTOR as a target for slowing aging, given that this is becoming an area of increased fundraising. To my eyes this is all irrelevant, of course. It isn't damage repair, it's just more metabolic manipulation that is exceedingly unlikely to meaningfully extend life in humans, even though it manages 20-30% life extension in mice, about half to two thirds of the effects of calorie restriction. Think of it as version 2.0 of the hubbub over sirtuins and resveratrol - that all went nowhere, generating only new knowledge, and the same will come of this, I think.

I'm not going to talk about tissue engineering, stem cells, or regenerative medicine this year. So much is going on that it would be a very long list: body parts and their components are being made, and researchers are just hitting their stride in this arena. The 2020s are going to be very interesting, as that is when we'll start to see a fair number of people with bioartificial replacements, augmentations, organ patches, and other treatments.

On cancer, again too much to point out. I leave that to others. But I will point to news on granulocyte transplant therapies: this has been a topic in past years because it seemed so very promising. It still looks promising, but by the sound of it this has run into the wall of grinding slow progress towards application, and the discovery of previously unappreciated complexity. But on the bright side, here are two and a half other ways to cure cancer.

Programmed aging as a viewpoint seems to be on the rise. Perhaps there are more publications, perhaps I'm just noticing more publications. This might be seen to be as much a threat to future funding of rejuvenation research as the continued focus of the mainstream of the research community on either doing nothing or working only on ways to manipulate metabolism with drugs to slightly slow aging. In the programmed aging worldview we should be working to restore epigenetic patterns and other aspects of metabolism to youthful levels, as they see this change as the root cause of aging. To their eyes damage repair is a waste of time. But this focus on altering metabolism is the doomed path to nowhere if aging is accumulated damage, as in the SENS viewpoint and - largely - the present mainstream view.

This year had its usual crop of short essays, links below:

I missed a hundred other interesting things in this short retrospective, of course - but that's why Fight Aging! has archives, and why you have free time.

Comments

Just out of curiosity, why do you think that the SENS AGE breaker research program will be the one to watch in 2014?

Is there something to make you think that this SENS research area is closer to an experimental breakthrough than the other SENS research areas?

Posted by: Jim at December 31, 2013 10:06 PM

@Jim: No secret knowledge. It just looks like the thread of SENS most likely to make it somewhere interesting in the next few years under current levels of funding. That has a little to do with the nature of the problem, and a little to do with the fact that this program is essentially very similar to existing drug development in structure, meaning it should be much easier to persuade other groups to join in under their own funding as progress is published.

The main issues with this field are infrastructural by my reading: there is little institutional support and knowledge for working with compounds like glucosepane, the primary target, and for-profit groups just aren't all that interested in funding this sort of groundwork. So there is a fair amount of tool building going on at the moment. Once that is done, it should open many doors.

Posted by: Reason at December 31, 2013 10:26 PM

Finally a link for the archives! I looked for it a lot of times, but never found.
I think it should be a good idea to put it somewhere on the home page...

Posted by: Aury78 at January 1, 2014 2:36 PM

@Aury78: There has always been a link to the archives on every page, in the right hand column under "Archives and Feeds".

Posted by: Reason at January 1, 2014 3:05 PM

I'm mystified by this: why does it seem so obvious to SENS-supporters that the supposedly smart people at Calico are likely not going to attack this problem in the proper way?

It seems like an absolutely critical time to be on the same page, does it not? I mean, Funding is always the limiting factor, from what I constantly hear from Aubrey...and here we have a huge investor who says publically they are interested in research-level work. Seems like a match made in heaven.

Are there philosophical differences that are at work? Why can we not agree on how to solve the problems? I thought the "7 deadlies" were virtually unassailable over the past 20 years, according to Aubrey? Do the folks at Calico not agree on the targets???

thanks,
Eugene

Posted by: Eugene at January 1, 2014 4:48 PM

@Eugene: SENS is still a minority position in the research community. A well-positioned minority position with many well-respected supporters, but nonetheless not reflective of the bulk of research. Yes, the causes of damage outlined in SENS are very well documented: that these changes exist is not arguable. But very few researchers are at this time interested in pursuing repair-based strategies. It is unfortunate that the bulk of research into aging and longevity will chew up vast sums to generate knowledge only, or slightly slow aging, or build marginal treatments for age-related conditions, but that is the present state of play.

My guess as to where Calico is going is informed by (a) past philanthropy on Google's part: very mainstream, very by the numbers, nothing remotely adventurous, and (b) the emerging details as to who is involved. None of the names brought up yet favor SENS, and all are very much more likely to follow a course that looks like the Longevity Dividend. That is to say ramp up development of drugs for metabolic and epigenetic manipulation to try to recreate calorie restriction or similar effects that slightly slow aging.

That will chew up a lot of money, and I predict do very little at the end of the day for people who are already old. Slowing aging is hard and it isn't rejuvenation.

Posted by: Reason at January 1, 2014 5:19 PM

@Eugene: Have a read of Reason's excellent essay "Dear Wealthy Individual, I Have This Great Idea Regarding How to Spend Your Money in a Better Way Than You Seem to Be Managing To Date" which is linked to in the above article.

One of the main points was that wealthy philanthropists invest in things that are already succeeding to some degree and have a large community around them. Frustrating, but that is the way things are.

Wealthy philanthropists who invest in less well known risky initiatives like Elon Musk are famous precisely because they are investing in things that aren't yet experiencing much success. Everyone thought Musk was absolutely crackers when he decided to start a private rocket company for example. You can count all the billionaires with this mindset on one hand.

Bootstrapping by dedicated individual scientists and a breakthrough demonstration in a mouse in one of the SENS is the most likely path forward.

Posted by: Jim at January 1, 2014 9:09 PM

@Jim, @Reason,

Your thoughts are much appreciated.

However, I'm not quite settled about a few things (and maybe I will not be anytime soon, but nevertheless...)

I understand about the wealthy-individual mindset; that makes sense to me, and it's reasonable, from their perspective. That was a good read (and there's so much more!)

So, irrespective of whether you solicit a wealthy individual or not, there still remains the problem of agreement amongst the *experts* on a few things, listed below. Because in reality, the experts are advising [well-informed] wealthy individuals about the direction of their funds, presumably(!):

1) Methodology. Does Art Levinson of Calico (or Ray K, or whomever) truly agree that the 7 Deadliest are THE target? How about the now defunct Ellison Medical? I don't get the impression yet from my limited self-education that this is true. So, why is SENS still a minority position, if in fact these are "well-documented"? Why then are researchers "not interested" in repair-based therapy?

It seems a debate is needed here, no? I'm no expert. Why should I believe SENS-based therapies to be more realistic than the others? I've read Aubrey's book going on 3 times now, but big deal, right? Does George Church now offer a substantive weight to the repair-based argument, for example? What is it about SENS that is not convincing to the research community? (forgive all the questions, perhaps they've been in answered in articles I've not read...yet)

2) Goal. The Longevity Dividend does not seem to be interested in significant longevity, now does it? It seems they are also trying to take into account healthcare spending, and solve that problem at the same time as adding 2.2 years ("but healthy ones!") onto our life-span. Calico offers some hope about it being "moonshot"...but then again, it does remind me of the language used in what I've read from Dividend.

Thanks,
Eugene

Posted by: Eugene at January 2, 2014 12:29 PM

@Eugene: Why isn't everyone working on SENS now that it's had ten years to percolate as something everyone in the field should know about?

1) Regulation makes it impossible to commercialize a treatment for aging. That has an effect at every level of funding for research and development.

2) It's much harder to raise funding for SENS-related stuff than for something that looks like drug development. See (1), and the general conservatism that makes new things harder to fund than proven adjustments to old things. Whether it will work well or not is irrelevant. If it looks like drug development, you can get funded. Gene therapy for people who don't have any condition that is acknowledged by regulators as actually being a medical condition - much harder.

3) Working on SENS would require a researcher interested in longevity to admit that their earlier work was ineffective, a wrong direction, etc.

4) The decades in which research community elders and movers and shakers ostracized anyone who talked seriously about life extension still have a weighing effect.

Posted by: Reason at January 3, 2014 4:29 PM

@Reason, well put.

So, #1 and #2 seem quite similar. I think this is key, what you said, "...Gene therapy for people who don't have any condition that is acknowledged by regulators as actually being a medical condition - much harder".

But here's the thing: Thankfully, I see that there is an "A4" trial for Alzheimer's. And if you refer to what Dr Sperling is saying, within the 1st minute of the video (http://www.youtube.com/watch?v=f3Q_yUAGdYQ - "Dr. Reisa Sperling, Harvard Medical School"), she talks about "prevention", and a "paradigm shift". That is, developing drugs that are preventative, not for after-the-disease-strikes applications. This, I feel, is HUGE. SENS can ride these coat-tails, I would suspect.

Further, Mike Kope of SENS says as much here: http://www.youtube.com/watch?v=StGn1abMjPo -- 2 or 3 minutes in. "serendipitously"...and again 6minutes in.

So, I think we need to take the grid that Aubrey shows with the 7 Deadlies...lately he matches-up Heart Disease, for example, and shows which of the 7, if addressed, will target the disease...(or Alzheimer's -- 3 of the 7 address that one, let's say).

So, like Dr. Sperling is saying, take advantage of the fact that there is a preventative opening here, regulation-wise! Pick a few aging diseases. Make sure they, together, 'cover' all of the 7 deadlies. Now, you have SENS validated in the currently-changing medical environment. But, those lines between the Deadlies and the Disease better be straight! :)

i.e. "we can prevent" Alzheimer's if we take care of 1,2, and 3 deadlies. We can 'lessen the risk of' (or whatever language is best) Heart Disease if we take care of Deadlies #4,5,6,7.

Mike K put it well at around 6min into his video above, "this could represent a move from a process-based model to a results-based model in the entire medical system." Again, huge.

But, am I missing some things here?
thanks,
Eugene

Posted by: Eugene at January 4, 2014 2:09 PM

@Eugene

I'm going to take a guess at why your above proposal isn't being carried out:

1. Even though repairing some of the seven SENS forms of damage should prevent Alzheimer's or heart disease, these forms of damage that your body cannot repair are not currently recognized as the causes of these diseases. Hence they are not 'theraputic targets' that the FDA would approve of in any application for a clinical trial.

There is a clear correlation between age and incidence of these diseases, but there is no conclusive proof that repairing this damage will prevent Alzheimer's or heart disease, as no one has yet created and tested the technology and techniques to carry out this experiment.

2. In the mainstream there is still a debate going on as to whether these forms of damage that the body cannot repair by itself are actually the cause of aging.

Although the SENS view of aging as accumulated damage is beginning to spread and win, this is still another point of doubt in the minds of anyone holding the purse strings of research grants or private pharma investment.

Until the investment (either for profit or public research) is 'de-risked' by removing these doubts, no one will invest. Unfortunately the only way to remove this doubt is to actually develop and carry out the technologies and techniques, which cannot been done quickly without investment. So things are stuck in a chicken and egg situation.

Posted by: Jim at January 18, 2014 10:52 PM
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