Health Extension #11: Aging – Death by Damage vs. Death by Design

Posted on July 28, 2013 by Scott Jackisch

Sorry for the provocative title, let me start by clarifying that I in no way subscribe to intelligent design. I am just trying to contrast the viewpoints of the two speakers that I saw at Health Extension Salon #11 last week: Cythia Kenyon and Justin Rebo. More on that later.

The Health Extension Salon was held at Runway SF this month, and it was outstanding as usual. I haven’t been getting out enough lately, so it was great to chat with interesting people and hear about amazing science. Runway SF, as you may know, is an incubator/co-work sort of thing in the Twitter building on Market Street in San Francisco. I guess it’s by invitation only. They have an igloo, and I saw some quadra-copters laying around and whatnot. So you know, it’s pretty cool.

I bumped into Hank Pellissier, who I first met years ago at my East Bay Futurist Meetup, and he told me a bit more about his new book, Brighter Brains. Hank has compiled a huge list of factors that affect intelligence from environmental factors to inbreeding. It seems like an interesting survey.

Then I listened in to a conversation with some blindingly smart people, R.J. and J.Y. among others, and wisely kept my mouth shut. J.Y. suggested that programmed death might be an adaptive trait that increases a species’ evolvability. More on that later as well. He also blew my mind by wondering aloud if the lunar cycles of women were a throwback to our ancient ancestors that dwelled in tidal pools. He pointed out that many illnesses varied in intensity of symptoms based on the time period during a woman’s menstrual cycle, but that the medical profession failed to take this into account when prescribing dosages of medicine. Thus, many women find themselves overdosed for half the month and underdosed for the other half. He suggested that there is a vast potential to exploit this to improve women’s health. I hope some bio-hackers look into this further.

J.Y. also suggested that anaphylaxis (like from a severe nut allergy) might be the result of a sort of epinephrine (adrenaline) regulation problem. This was an idea his young child apparently suggested upon learning that an epinephrine injection was the only reliable treatment. From the mouth of babes. I got the impression that J.Y. was brimming with ideas for potential medical breakthroughs.

Before introducing the speakers, the charismatic and charming Dinelle Lucchesi challenged the crowd to call out potential roadblocks standing in the way of progress in anti-aging research. There was some disagreement about whether the fact that aging is not designated as an illness by the FDA is an issue. Justin Rebo thought this was unimportant since any effective anti-aging treatment would be sure to combat any number of illnesses. It was also suggested that aging is difficult to measure with bio-markers. But my favorite roadblock was that “biology is hard.” Yep, that sums it up.

Health Extension founder and awesome person, Joe Betts-LaCroix, then took to the stage to reiterate the fact that aging research is underfunded:

Most healthcare money treats age-related diseases.
Aging is the single biggest risk factor for these diseases.
But funding to address the biochemical processes of aging is <0.01% of healthcare spending!

Typical shortsighted narrow-mindedness prevents us from exploring preventative medicine to the degree that we should. But I was also excited to hear that Health Extension has commissioned a study by students from Moscow’s Skolkovo Management School * to make a quantitative case for more funding in aging research. I guess Joe will be heading off to Washington with this in hand to beat Congressmen over the head with it or something. I wish him the best of luck, but he might be better off packing a suitcase full of money.

The first guest presenter of the evening was Justin Rebo, CEO of Open Biotechnology. In 2009, working with SENS, he built a device to filter out senescent immune cells from the blood. This mechanism was interesting in that he attached metallic particles to antibodies which selectively bound to defective T cells, and then was able to pull them from the blood using a magnet. There is something brutal and almost mechanical about this approach. I like it. I guess it might help with the ineffectiveness of flu vaccines for the old. This blood scrubber seems to be something like a dialysis machine in that it filters all the blood of an animal and replaces it. This work focuses on bioremediation of the blood, which reminds me of the work being done around rejuvenation of old mice using blood from young mice. Rebo is now working on a new version of this device, which will add positive factors in addition to removing the negative ones. He sees great promise in getting the blood compounds of older creatures to match the levels found in young animals.

So Rebo’s approach seems well aligned with the SENS model, in that it both treats aging as an accumulation of damage and toxins and seeks to remediate the damage. This looks to be a sensible short-term solution (Well, except for this whole move the mitochondrial DNA into the nucleus business, that seems crazy. But what do I know?). The next speaker of the evening seemed to suggest a deeper cause of aging: it’s programmed by our genes.

Cynthia Kenyon is a distinguished scientist based at UCSF:

In 1993, Kenyon and colleagues’ discovery that a single gene mutation could double the lifespan of C. elegans sparked an intensive study of the molecular biology of aging. These findings have now led to the discovery that an evolutionarily conserved hormone signaling system controls aging in other organisms as well, including mammals.

– from her Biosketch

She gave a presentation similar to her 2011 TED Talk, which is definitely worth watching. Kenyon’s sparkling wit is a pleasure to experience. The upshot of her presentation was that this longevity mutation she found in C. elegans (Daf-2) somewhat impaired the worms ability to bind to insulin and IGF-1, and this caused another gene called Daf-16 (if it was in the nucleus) to trigger all sorts of protective pathways and thus extend life **. Sugar impairs this process, which is why Kenyon reluctantly admits that she eats a low glycemic diet. This was a big topic of interest among the folks that thronged her with questions after her talk. But Kenyon is a real scientist and cautiously avoided advocating for this diet since she says it hasn’t been proven to extend life.

As I mulled the two presentations over preparing to write this post, it occurred to me that there was some tension between the two talks. Rebo and SENS are boldly striding ahead assuming that aging is a process of damage and that we can combat it by repairing damage. But Kenyon seems to suggest a deeper, perhaps longer-term strategy of activating the body’s built in protective pathways to extend life. She prefers small molecules for this, since they are easier to test. Also, this modulation requires some finesse. You can’t just go knocking genes out entirely. If you couldn’t bind insulin at all, that would be a problem.

Kenyon’s work also suggests that aging might be a process that is controlled by genetic timers. “How does the body know when menopause should occur?” she mused. Perhaps the entire aging process is carefully timed by genetic pathways. Maybe age-related death is an adaptive trait. Wait, what? Yep. Think back to what J.Y. said earlier. Death improves evolvability. You would expect that an organism that died on a timer to evolve more. Consider an environment that can support 100 organisms. The more frequently those creatures die (assuming they can still reproduce), the greater the genetic diversity. Uh, maybe I better stop here and go ask Razib.

For the sake of argument, let’s just say that aging and death are programmed, and that this does improve evolvability. Well that suggests that the “repair the damage” guys are missing the boat somewhat. After all, the body seems to have these protective pathways waiting to be activated. That’s sort of how calorie restriction might work. It tricks the body into activating protective genetic pathways. Because a timed death is fine as long as you get to reproduce, but during time of stress, such as famine, our genes have a special bag of tricks that can help us survive.

But there is a further twist. Kenyon mentioned that deactivating sensory input extends life in fruit flies. They can’t sense their food and thus live longer. I guess it has been shown that insulin rises more if you smell food. So you calorie restriction people are best off skipping dinner with non-CR friends entirely. It’s not just the food itself, but the signal of the food, that works it’s way into your genetic expression somehow.

But now we are getting into hormesis territory. Someone get Seth Roberts on the phone. A little bit of toxin triggers the body’s natural defenses. Kenyon pointed out that mildly inhibited respiration was associated with extended lifespans and wondered if the resulting increase in toxins such as ROS were the cause. Get my homeopathist on the phone. So are the small amounts of herbicide on that non-organic food I disdain actually helpful? Oh brother, now I have to rethink everything. Maybe the SENS people should too, given that some of the supposedly damaging toxins like amyloid plaques might turn out to be protective mechanisms. I guess this goes back to my favorite quote of the evening, “Biology is hard.”

Overall, I was impressed by both speakers. Both the pragmatic Rebo and the deeply insightful Kenyon are striving to extend human health spans. I don’t want to lose sight of this when I drill down into the details. At the end of the day, successful anti-aging treatments will reduce suffering and increase health and happiness. Imagine an 80-year-old as vibrant and healthy as a 20-year-old. Even if I dropped dead right at 81, I would take that sort of old age in a heartbeat. It’s a real shame that these aging researchers are so bereft of funding. If anyone reading this knows any good policy wonks or lobbyists who care about longevity, you should direct them to the next Health Extension Salon so they can get involved. Hey, I’m doing my part. I’m getting the word out.

* Skolkovo might be the world’s coolest looking school by the way.

** It’s worth noting that at least some of Kenyon’s insulin/IGF mutants had normal reproduction. http://rstb.royalsocietypublishing.org/content/366/1561/9.full Thus there doesn’t seem to be a tradeoff between fertility and longevity.

Foresight 2013 – Day 3, Part 2

Posted on January 17, 2013 by Scott Jackisch

This article is a continuation of my commentary on the Foresight 2013 conference. As I mentioned in my Day 1, Day 2, and Day 3 posts, the Foresight folks have a strict media policy in place. So while I can’t really blog about the content of the presentations, I will discuss the work these speakers have previously made public.

I would love to say that anyone who thinks they understand quantum mechanics doesn’t understand quantum mechanics, but I really just don’t understand it. When Harvard’s Alan Aspuru-Guzik gave his Foresight 2013 talk “Simulating Quantum Mechanics with Quantum Devices,” I listened with more enthusiasm than comprehension. So bear with me. Aspuru-Guzik likes to use quantum simulation to go after electronic structure calculations which are some of the most computationally intensive problems in science. “The calculation time for the energy of atoms and molecules scales exponentially with system size on a classical computer but polynomially using quantum algorithms.” Aspuru-Guzik points out that theory is ahead of experimentation in this field, but he has found and built some toys to play with.

So the idea here is to leverage quantum devices to simulate quantum mechanics. I guess the NIST has some device with hundreds of qubits. But the systems Aspuru-Guzik gets to play with are more modest. He ran a simplified protein folding problem on an 81 qubit D-Wave system and got 13 correct results out of 10000 runs. “The fact that it worked at all was significant.” The investors must be thrilled. I have heard that aside from factoring numbers, there aren’t many uses for this quantum computing. But if you can factor numbers, you basically break all encryption. Of course when I say “you” I mean the NSA. But Aspuru-Guzik’s stuff is more benign. He will be folding proteins and figuring out photosynthesis and stuff. So he’s cool.

Next, Gerhard Klimek gave a talk about Nanohub.org. Here’s what they say about themselves:

What is nanoHUB.org?

nanoHUB.org is the place for computational nanotechnology research, education, and collaboration. nanoHUB hosts a rapidly growing collection of Simulation Programs for nanoscale phenomena that run in the cloud and are accessed through your web browser. In addition there are Online Presentations, Courses, Learning Modules, Podcasts, Animations, Teaching Materials, and more to help you learn about the simulation programs and about nanotechnology. nanoHUB supports collaboration via Workspaces and User groups.

So there are clearly educational resources for students, but I understand that researchers and industry folks get into the simulation stuff. Boasting 900 papers with an h-index of 41, Nanohub is a serious scientific resource. So why head head on over and simulate a carbon nanotube or something?

Carrying on in the simulation vein, Ron Dror of D.E. Shaw Research talked about their custom supercomputer, Anton. Anton is a massively parallel ASIC based pocket calculator that can figure out how drugs bind to receptors. Dror has published work on G-protein-coupled receptor modulators in particular, which represent one third of all drugs. Who knew? Pretty cool stuff. And this David E. Shaw fellow is an “intriguing and mysterious” character. He saunters from his Stanford PhD over to Columbia, toys with parallel supercomputing, yawns, strolls down to Wall Street, dabbles with high frequency trading, stretches, casually sets aside the resulting $27 billion hedge fund and sets up a computational biochemistry research group to model molecular dynamics simulations of proteins. What a slacker.

Topping off the conference was the venerable CalTech theorist, William A. Goddard, III. Your guess is as good as mine as to what he said… and I was in the audience. There was something about a ReaxFF force field which lets you model chemical reactions. He also said he was happy to see theory starting to be able to predict something useful, which I am sure is a huge understatement. But there was just too much math for me to really get a grasp on his talk.

I was incredibly awed by these sober scientists toiling away at the edge of human knowledge, delving into the the very underpinnings of chemistry and biology.What new wonders will be within our grasp as we come to understand and manipulate complex molecular interactions at the atomic level? Dare I hope for my beloved utility fog someday? If so, we will have them to thank. And uh, possibly pay royalties to, depending on how the IP plays out.

Foresight 2013 – Day 1

Posted on January 12, 2013 by Scott Jackisch

I attended the first day of the Foresight 2013 nanotechnology conference today. They have a very strict media policy in place this year since some speakers will be discussing pre-publication findings and they don’t want their publication hopes destroyed because some foolish blogger spilled the beans. So I am not supposed to blog about anything I heard today unless it was already public. My friend Jeremy told me that most of the presentations were already public as far as he could tell, but I had the rare pleasure of chatting with some scientists who did share juicy tidbits.

For those that don’t know, the Foresight Institute is an organization devoted to promoting the upside and avoiding the dangers of transformative future technologies. Their primary focus is on nanotechnology and it’s ultimate expression: molecular manufacturing as expressed in Feynman’s “There’s Plenty of Room at the Bottom” talk. And of course Drexler’s Engines of Creation developed these ideas further. So this is pretty technical stuff and the Foresight 2013 conference was the most academically focused futurist conference I have attended. Several attendees even remarked that it was more academic than previous years. I attended in 2010 for the great Moldbug/Hanson debate and again in 2011 at Google when they had a more entrepreneurial focus. I guess those were less academic. But my brain melted slightly in the blast furnace of atomic scale physics each time.

I like to challenge myself with these things, trying to absorb some fractional understanding of the work presented by these top scientists in highly specialized fields. People looked at me askance previous years when I told them I was just a layman interested in the field. This year I lamely suggested that I was a blogger of some sort and found that this was not more ingratiating given the media ban. Fortunately for me, I am shameless and slightly pushy in conversation so I manage to get my ears filled up with some amazing ideas even if I do barely comprehend them. Being a generalist, I am biased toward the idea that everyone is a laymen in fields other than their own. I hope that I can help pollinate ideas across fields with my writing some day.

Given my interest in computers, one of my favorite Foresight presentations so far this year was a talk by Purdue professor, Gerhard Klimeck about single atom transistors. Luckily, I found a similar presentation already posted on Nanohub.org, so I will talk about that. One key point worth noting is that cpu performance is really constrained by power consumption. We get more transistors but clock speed and performance per clock cycle has been pretty much flat since 2005. Which is why parallel computing is so important. But in spite of the nifty .NET tools mentioned in the link above, parallel code is still harder to write and largely under-utilized. This is something that Paul Graham has carped about with his ambitious startup idea: Bring Back Moore’s Law. And of course it smacks of Theil’s stagnation of innovation schtick. But I’m sure Ray isn’t worried. He knows a paradigm shift will save the day.

So wait, oh yeah, power consumption occurs when circuits are switched and via leakage. In fact, as much power is supposedly lost via leakage as from switching. So your CPU is constantly leaking juice. Disgusting. So these single atom transistors come riding to the rescue since they have less leakage. But Klimeck’s main contribution to this effort is the Nemo5 software which enables researchers to model “atomic-resolution calculation of nanostructure properties.” Modeling is a key enabler of all design I guess, and this Nemo software seems to have a broad range of uses from academia to industry. Good on him and his group. Where would our Singularity be without them?

I really wish I could talk more about my amazing conversations tonight, but I will just link to this one paper which is already public but whose significance has not yet been widely appreciated: Neutral Atoms Behave Much Like Classical Spherical Capacitors. If you are a super-genius, I assume it will be obvious to you why this is important. Listening to this idea connected to a bunch of other ideas gave me some glimmer of insight into the matter, but it will all be made more clear by forthcoming publications. Stay tuned to your physics news feeds, friends.