The only events I can seem to attend these days are Health Extension Salons.  But I also attended the 2013 Quantified Self Conference in San Francisco, so I was exposed to plenty of new ideas there as well, which I will be sharing soon.  Health Extension Salon #13 was held at Runway SF, which is a cross between a co-working space and an incubator.  At the beginning of the talks, the operations person from Runway said that their uniquely high percentage of shared public space supercharged the startups based there as the teams intermingled and ideas were cross-pollinated.  Apparently they have have a good number of successful exits, which for an incubator must mean getting funding or something.  It’s an amazing space, but they are still pretty stealthy.  They don’t even have a website that I could locate.

For those who don’t know:

The Health Extension community is committed to collaborative action to extend healthy and happy human life spans to 123 years and beyond. Our members are scientists, entrepreneurs, and social influencers dedicated to fixing the degenerative cellular processes that cause deadly human diseases.

Health Extension was founded and is executively directed by scientist/entrepreneur Joe Betts-LaCroix.  Joe gave his standard presentation pointing out how absurdly underfunded aging related research is.  Basic research into the biochemical processes behind aging represent a tiny fraction of healthcare spending, while aging related diseases account for the vast majority of healthcare costs.  So obviously there is a disconnect somewhere.

The field of aging research it clearly underfunded, so Google’s new Calico project seems very encouraging.  Aubrey De Grey is certainly in favor of it.  Google clearly has cash to throw at the problem, but some folks question whether they can find the right talent.  However, accomplished biotech scientists have assured me that Calico’s CEO Arthur Levinson has an extraordinary contact list and can get the talent he wants.  So the hunt is on in earnest with the data wizards over at Google on the case.

Joe highlighted some very interesting findings by researchers at the University of Pittsburgh School of Medicine.  They looked at lymph nodes and reconsidered why cancers often begin their deadly migration of metastasis there.  Lymph nodes provide direct access to nutrients, growth factors, and signaling proteins that aid in cell recruitment.  Then they turned this idea on its head and asked – “Hey, why don’t we see if we can grow little mini-organs there in the lymph nodes?”  And so they did.  They injected mouse lymph nodes with liver cells, and the little masses of liver cells that grew in the lymph nodes were functional enough to save the mouse from liver failure.  Then they performed the same trick with thymus cells and pancreatic cells.  So yeah, that sort of blew my mind.

When you stop to think about it, you can imagine ways to make all organs fault tolerant by overloading lymph nodes with little micro-organs distributed throughout the body.  This almost reminds me of highly-available computer clusters.  Of course, evolution probably arrived at a centralized liver for a reason.  It may be that a single large mass of liver tissue can more quickly transfer bigger doses of important factors like glycogen to other vital organs.  Messing with any complex system like this will surely lead to a bunch of broken functions.  But if I were faced with the choice of that or liver failure, I might take the chance.  There aren’t enough donor livers to go around.

Next, Joe went on to relate that HE’s Aging Variant Database Project was rejected by the Nucleic Acid Research journal.  Apparently an editor fell victim to the halo effect bias.   They decided that the database must be tainted because it was hosted on a site that also hosted links to life extension topics and the mere mention of life extension is disreputable.  This database is a meta-analysis of existing studies meant to identify genetic variants related to aging.  This certainly isn’t quackery or pseudo-science and most of the reviewers realized that.  But Nucleic Acid Research is a prestigious journal.  And prestige is something that must be jealously guarded.  So the Health Extension researchers will be submitting the Aging Variant Database to another journal, possibly the modern, open-source PLOS One.

One thing I like about Health Extension is all the interesting people you can meet during the social periods.  I bumped into biotech entrepreneur and fellow Oaklander Ryan Bethencourt, who co-founded Sudo Room, Counter Culture Labs, and BerkeleyBiolabs.   He told me a bit about this “hackubator” Berkley Biolabs is setting up, which is biotech space for scientists with promising ideas to work out proofs of concept.   I guess there is this new crowdfunding site, Wefunder.com, that will be involved somehow. He then introduced me to Andre Watson, who won my admiration first by having seen every Star Trek episode, and secondly by telling me a bit about his work on nanotechnology for genome editing.  At Foresight this year, I had heard George Church mention the CRISPR gene editing technique that is a biomimicry of a bacterial proto-immune system.  So accurate human gene editing therapies might be coming down the pipe at some point.

As much I do love Star Trek (Picard not Kirk), I have this dark side that is contrary to the Gene Roddenberry optimism of Star Trek.  I am picturing governments editing the genes of their citizenry to make them more pliable.  Imagine the marketing potential there!  I asked Andre if he thought gene editing would be used for good or evil, and he sensibly replied “both.”  Which is, of course, the fate of all technology.  But a world where genes can be altered at will or against your will is very strange to imagine.  Will genetic traits be taken up and discarded like fashion statements?  Will we accidentally break all manner of delicately balanced genetic network interactions and wreak untold havoc?  It’s hard to say.

I then went on to talk to another scientist that I admire, JR, to hear what he was up to.  I had been wondering why SENS didn’t seem to be pursuing a strategy to activate protective pathways that prevent aging, similar to what Cynthia Kenyon found in her long-lived nematode mutants.  JR pointed out that since calorie restriction doesn’t even seem to increase longevity in mice, let alone primates, it would be difficult to exploit those pathways that Kenyon discovered.  He framed the question thus: would it be easier to tweak metabolism to prevent damage or to repair damage once it occurred?  He considered the latter to be simpler.  And this seems consistent with the SENS approach.  Repair damage as it occurs.  And that is perfectly reasonable, but I find myself a bit disappointed.  Kenyon seemed to point toward hidden capabilities just waiting to be unlocked.  Like a biological equivalent of the software Easter egg.  But practical people are pointing to something more like automobile maintenance.  Not that I would turn down longevity via that method.  I just want to believe I can fly.

Err, yeah. So then JR clued me into the immense potential of bone marrow transplants.  These have been found to “cure” AIDS.  It’s not clear how this applies to his own work, but he does like to work with blood because it’s easier to manipulate than organs or solid tissues.  See, this is why I like JR so much.  His approach appeals to my pragmatic side.  I look forward to seeing what practical human rejuvenation techniques he will develop.

Again, this is why I love Health Extension Salons.  I have already been inundated with exciting ideas and the main speaker hasn’t even presented yet.  The main speaker was Sean Mooney, Director of Bioinformatics at the Buck Institute for Research on Aging.  He started out by encouraging biotech startups to consider government SBIR and STTR grants to access non-dilutive capital.  He, like many academics, sits on various “study sections” that review these grants and said that he often doesn’t see enough projects worth funding.   I had never heard of these study sections, but I guess the recent government shutdown really threw a wrench into the works and some think that this threatens the US position as the worldwide leader in scientific research.  Of course my libertarian friends would have something to say in rebuttal, I’m sure.

Mooney then asked the room how many people had their entire genome sequenced. I initially raised my hand, foolishly thinking that my paltry 23andMe SNPs qualified.  But Mooney repeated the phrase “entire genome.”  And only one person raised their hand.  Apparently they had participated in a study through Personalis.  Mooney was impressed and said that he had asked that question at many conferences but rarely had anyone raise their hand.  He predicted that the entire genome sequencing would become very common as soon as the price plummets.  And the price is plummeting exponentially in a way that would warm Ray Kurtzweil’s heart.

<insert logarithmic graph here>

Mooney talked a bit about his work in translational research, which aims to bridge the gap between basic and applied research to move findings from research labs into medical clinics and move empirical data from the clinics back into the research labs.  This is a fascinating topic that certainly warrants further examination, but then Mooney went on to an even more interesting topic.  He brought up the CAGI challenge, which invited researchers to predict clinical medical outcomes based on genomic data using George Church’s Personal Genomes Project.  Currently, 23andMe gives you some estimates of that sort of thing for many diseases, but apparently their stuff doesn’t cut the mustard in the clinical world.  So this was a pretty tough challenge and actually none of the teams were able to accurately match more than a small minority of the genomes to medical outcomes.  I found this surprising.  I would have expected better results.  It’s not clear if this poor showing was the result of insufficient data, or if nurture really does trump nature in medical outcomes.  I understand that throwing methylation information into the mix would help improve the predictive power.  One biologist I related these finding to quipped that he wasn’t surprised by the results since DNA can’t tell you whether a person is alive or dead.

So what does this mean?  It seems to mean that scientists don’t yet have good models to predict what the real effect of genes are on phenotypes.  Yeah, so what good is this genetic data then?  Best take those 23andMe predictions with a grain of salt.  Mooney was quick to point out that he obviously wasn’t bearish on genomics being a bioinformatics person.  While genetic data might not be ready for clinical prime time, he had little doubt that doctors will be using genetic data in the near future.

One challenge to reaching this goal is that gene expression differs from tissue to tissue.  It was speculated during discussion after the talk that these differences in gene expression could pose unforeseen risks to Induced Pluripotent Stem Cell treatments.  Consider a cheek cell which expressed a mutation that increased the chance of liver disease.  This would be harmless since the cheek cell isn’t in the liver, but if that cell were scraped and converted into a stem cell to regrow liver tissue… well, that would be a problem.  At first, I naively thought that IPS stem cells would be better for medicine since the immune system wouldn’t need to be suppressed to avoid rejection.  But several scientists I spoke with pointed out that the complexity of modifying IPS posed more risks than naturally pluripotent embryonic stem cells, though having your own cord blood would be optimal.  Anyone have parents forward thinking enough to bank that stuff?  No?  Too bad.

Health Extension continues to provide an amazing forum to learn about real science from serious scientists who are pushing the field of aging research forward.  The more I learn about this stuff, the more daunting the problems seem sometimes.  But there are other ideas that seem so much closer to implementation, such as Justin Rebo’s blood scrubber, or even the idea of blood infusions from young to old to provide regeneration.  Health Extension is a real thing that can happen if the right resources are focused upon it, and that’s an exciting future to consider.

As is my habit, I attended Health Extension #12 at the new Hacker Dojo in Mountain View this past week.   The new Hacker Dojo location seems bigger and more professional than their old place.  This hackerspace has a clean, organized air about it which reflects its location in Silicon Valley.  NoiseBridge in SF and SudoRoom in Oakland both seem more anarchistic.  I want to go back sometime and check it out more thoroughly though.  I love hackerspaces.  But one of the Hacker Dojo members was complaining to me about freeloaders.  So it seems that Hacker Dojo is subject to the same problems that plague all attempts at direct democracy. Saying that everyone is in charge is equivalent to saying no one is in charge.  The direct democracy folks will need to work a bit harder to outdo the framers of the Constitution.  Representative democracy, get into it.

Hacker Dojo’s new digs at 599 Fairchild in Mountain View, CA.  It’s more built-out than this now.

Joe Betts-LaCroix gave a summary of the Health Extension mission and an update on their current activities.  The bottom line is that aging research is seriously underfunded.  Health care costs consume 17% of US GDP, and up to 90% of that spending is on age-related diseases.  We simply can’t afford to continue ignoring the biochemical processes of aging.  We need to spend on effective preventative medicine.  He also reported that the Health Extension pipeline is operational.   So researchers with great aging research ideas that are vetted by the HE Scientific Advisory Board will get assistance with funding and support from a variety of potential sources such as venture capital or philanthropic funds.

Joe next trotted out a fancy new refactoring of the word “aging”:

Degenerative Precursors – Any process, condition, or diagnostic result that, if unchanged, correlates with a high probability of subsequently developing any of a list of at least two, otherwise disparate age-related diseases.

He ran this by a bunch of biologists and they came up with a big honking list of “degenerative precursor” candidates, so let’s see where they go with this.  The HE 2013 internship project already produced “the world’s first comprehensive database of all known genetic variations in humans that pertain to lifespan and aging characteristics.”  It’s available online now, and they have submitted the results to a prestigious journal for review.  So these people don’t mess around.  I’ve heard many researchers suggest that a vast store of answers lay undiscovered within the massive corpus of existing research.  Don Swanson pioneered this sort of literature-based discovery which I learned about at a Samuel Arbesman talk last year.    This sort of meta-study is probably going to be more and more important as the amount of research explodes.

Joe also gave a plug to the upcoming SENS Reimagine Aging Conference in Cambridge, UK.

This month’s Health Extension featured leading Alzheimer’s researcher J. Wesson Ashford, MD, PhD.  Dr. Ashford was instrumental in developing anticholinesterase therapy, which is now standard treatment for Alzheimer’s disease.  He is now the director of the War Related Illness and Injury Study Center the VA Palo Alto Health Care System, and clinical professor of psychiatry and behavioral sciences at Stanford University. He is chair of the Memory Screening Advisory Board of the Alzheimer’s Foundation of America and clinical editor of the Journal of Alzheimer’s disease.  So this guy knows his Alzheimer’s.

Ashford started out his talk by telling the crowd that we were all going to die, which wasn’t well received by a bunch of life extension enthusiasts.  However, he tried to put things into perspective by pointing out that the Milky Way and Andromeda galaxies are due to collide in about 4 billion years, which certainly makes me feel better about dying.

He went on to point out that one of Joe Betts-LaCroix’s standard slides showing age-related diseases would be more clear if plotted on a logarithmic scale.  He referred to the Gompertz Law of Mortality, which states that mortality increases exponentially over time starting around age 30.

 So the chart above would look like the chart below if mapped to  log scale, get it?

Simply put, the older you get, the more likely you are to die.  And this is a regular progression, not a sudden jump as the first slide might make it seem.  Wesson seemed to be making a fatalist point: time kills – period.  But Health Extension might be able to use this point of view to tweak their message.  Folks ought to take aging more seriously if they consider that our risk of death is doubling every year over thirty.

Dr. Ashford pointed out that the exact cause of Alzheimer’s is still not known, but there are several schools of thought on the matter.  The Beta-Amyloid theory has been the prevalent theory for over 100 years and suggests that the plaques that build up in the brains of Alzheimer’s patients are the cause of the condition.  However, several drugs have successfully removed these plaques, but failed to improve the symptoms of Alzheimer’s disease.  So that has lead some, including Ashford, to conclude that this theory is flawed and that billions of dollars have been wasted by drug companies.  He made the reasonable point that the role of factors should be understood before attempts were made to remove them from the body.

The Tau theory is that a process called “Tau hyperphosphorylation” leads to tangles that clog up the neuron and prevent it from functioning.  This occurs in the later stages of Alzheimer’s disease and is related to dementia.  Ashford himself subscribes to a theory which I didn’t really understand.  But he seemed to suggest that attention should be focused on another protein that is created when beta-amyloids are cleaved from their precursor protein.  I couldn’t find the name of this creature, but I will ask around.  But it seems that Ashford thinks that the real action is happening inside the cell and the extracellular plaques are a red herring.

Dr. Ashford made some provocative comments that people don’t care about genetics, cost-benefit analysis, or the future.  His case for genetics centered around his assertion that not enough people are using 23andMe.  Also, he lamented that not enough of the papers being submitted to Journal of Alzheimer’s disease are controlling for the apoE gene, which has a major impact on Alzheimer’s risk.  This gene has three variations: APOE-2 reduces likelihood of Alzheimer’s, APOE-3 has average risk, and APOE-4 confers increased risk.  I checked my 23andMe report and was relieved to find an APOE-2 in there.  But of course, if I had an APOE-4 I wouldn’t… err, what was I saying?  Never mind.  Actually, I shouldn’t joke about this stuff.  Folks with a couple of APOE-4’s should consider taking extra preventative measures.

Here are the preventative tips I got from Dr. Ashford’s website:

THE TOP TEN TREATMENTS FOR PREVENTING ALZHEIMER’S DISEASE
J. Wesson Ashford, M.D., Ph.D. (November, 2006)

1. Take your blood pressure regularly; be sure that the systolic pressure is always less than 130.

2. Watch your cholesterol; if your cholesterol is elevated (above 200), talk to your clinician about appropriate treatment. Consider “statin” medications a d besure your cholesterol is fully controlled. Increase your dietary intake of omega-3-fatty acids (eat deep-sea finned fish at least 3 times per week) and nuts (especially almonds).

3. Exercise your body, mind, and spirit regularly. Physical exercise best 10-30 mins after each meal for 10-30 minutes, 3 times per day. Do aerobic and strengthening exercises. Maximize your education. If you have spare time, do mental puzzles (like crossword puzzles). Stay active with your friends and in your community.

4. Physically protect your brain. Wear your car seat-belt. Wear a helmet when you are riding a bicycle or participating in any activity where you might hit your head. Work to decrease your fall risk through physical exercise, making your environment safe.

5. Keep your BMI (Body Mass Index) in the optimal range (19-25):
   ——– BMI = 703 * weight (pounds) / height (inches) squared ——–
   To optimize your BMI, control your food intake and exercise. Decrease your risk of type II diabetes. Monitor your fasting blood sugar yearly. If you have diabetes, make sure that your blood sugar is optimally controlled.

6. Consult your clinician about your joint and muscle pains (treat arthritis with ibuprofen, sulindac, or indomethacin).

7. Take your vitamins daily (folate – 400mcg, B12 – 25mcg, C – 250 mg, and E – 200iu’s). Check with your clinician yearly to be sure your homocysteine levels are not high and you have no signs of or risk factors for B12 deficiency (ask your doctor to make sure your B12 level is above 400. If diet doesn’t help, take oral supplement. If oral supplement doesn’t work, get monthly B12 shots additionally. Maximize your vegetables.

8. Keep your hormones stable. Check with you clinician about your thyroid hormone. Discuss sex-hormone replacement therapy with your clinician (such therapy is not currently recommended for Alzheimer prevention, but may help memory and mood).

9. If you have difficulty getting to sleep, consider trying 3 – 6 milligrams of melatonin at bedtime. If you snore, consult your clinician about sleep apnea.

10. Monitor your memory regularly; have your memory screened yearly. Be sure the people around you are not concerned about your memory. If you think that you have significant difficulty with your memory, talk to your clinician about further evaluation. Consider therapy with cholinesterase inhibitors and memantine.

source: http://www.medafile.com/top10tr.htm
more tips here: http://www.memtrax.com/en/yourBrainHealth

It was also suggested that low doses of ibuprofen might be preventative of AD in a way similar to the way that people take small regular doses of asprin.

Ashford has developed a memory diagnostic tool at http://www.memtrax.com to help detect memory degradation associated with Alzheimer’s as early as possible.  I signed up and tried it out, and it involves viewing a series of pictures and hitting the space bar when a picture is repeated.  It was fairly easy and more of a test than a task, like Dual N-Back or Lumosity.com.  It seems to be free and it’s cool that Ashford is putting it out there to help folks out.  He also sees huge potential for big data and web applications to enable memory testing across broad populations.  This is the sort of area where Quantified Self type data can cross over into real science.

After the talk, I got into a discussion with a Silicon Valley entrepreneur type who was skeptical about Health Extension.  It’s illuminating to discuss your beliefs with a skeptic that doesn’t listen very closely.  All of the sloppiness and jargony shorthand which is acceptable when preaching to the choir gets called into question.

So why am I in favor of health extension after all?  I think the key lays in the distinction between life extension and health extension.  No one wants to live 50 additional years in the poor health of a typical 80 year old today.  The goal is to extend the period of health for humans.  That’s a big deal.  It would lead to a huge reduction in suffering worldwide, massive economic benefits for states burdened with high health costs, and it’s just what I want for myself and my own loved ones here and now.

Of course this skeptic brought up the standard Malthusian argument that the earth couldn’t sustain humans with extended health spans.  In response, I brought up the Haber process which is an example of how human ingenuity throws a wrench into Malthusian calculations.  The Haber process extracts nitrogen from the air in the form of ammonia.  Big deal, right?  Well fertilizer generated from ammonia produced by the Haber process is estimated to be responsible for sustaining one-third of the Earth’s population.  So when we consider the sustainability of life extension, we should consider what other breakthroughs like the Haber process lay around the corner.

The flip side of this argument is that a ballooning Haber enabled population is degrading the earth at a more rapid pace.  I might argue that folks who oppose health extension on sustainability grounds should consider that the poverty induced high reproductive rates of the developing world probably dwarf any environmental impact that health extension might have.  Arguments about the stagnation of innovation notwithstanding, I will assert that humans are inventive enough to increase efficiencies, and sensible enough to reign in fertility, as their conditions improve.  So let’s go help pull the Global South out of poverty so that their fertility rates go down to more manageable levels and work on health extension.

Another point that came up that evening was this common Silicon Valley refrain that startup founders need to stop focusing on minor first world problems and start tackling the real problems of the world.  At the same time we hear that VCs have turned cowardly and are now demanding that startups have an established customer base and revenue before they will dip a tremulous toe into the water and risk their precious cash.  So the problem is probably not founders without vision, as much as capital without guts.

Overall this was an interesting evening that touched on a range of topics.  Alzheimer’s disease is a serious illness that will probably increase in frequency as the population ages and lifespans continue their historical increase.  It may be that the big drug companies need to slow down and dig deeper into the fundamental biological processes underpinning this disease in order to come up with truly effective treatments.  I admire the work of researchers such as Dr. Ashford, who tirelessly probe into the maddening complexities of human biology looking for these answers.  Even if he is a fatalist who insists that we are all doomed to die in the nearing galactic traffic accident.