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

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:

  1. Most healthcare money treats age-related diseases.

  2. Aging is the single biggest risk factor for these diseases.

  3. 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. Thus there doesn’t seem to be a tradeoff between fertility and longevity.

Quantified Self: What am I tracking and why?

Quantified Self

If you aren’t familiar with Quantified Self, it’s basically a group for people who are tracking information about themselves such as the number of hours they slept or how many calories they have eaten each day.  Some people do this to solve tricky health problems, others are trying to optimize their own health or behavior.  Some just love lots of data and graphs and such.  QS was started by Wired founder Kevin Kelly as an informal group meeting in his living room but has grown into an international phenomenon.

Why do I track?

I am not as into self-quantifying as some people are, but I do want to optimize my health and my behavior to some extent.  I don’t really like the word optimize in this context, but I am already relatively healthy and functional so I guess it fits.  Supposedly you can manage what you measure, so it makes sense to measure things that are important or that you suspect or correlated to important things.

What is important to me?

A big motivation for my own tracking came from wanting to write more.  I don’t want to just be an IT guy for the rest of my life, so I wanted to change my own behavior to include more writing.  That is why I got into Habit Design and willpower.  I am also interested in longevity and intelligence.  I want to extend my bodily and cognitive health span as much as possible.

What do I track and how?

Currently, I am using a Fitbit One to track my physical activity.  I’ve used simple pedometers before but this new Fitbit is crazy.  It records steps, distance, flights of stairs climbed, and even sleep.  Sleep?  Well it records how still you are in bed anyway.  It’s not as cool as a Zeo, but it seems less intrusive to strap on the Fitbit wristband than the Zeo headband.  Fitbit has a free website to view your data, but you can’t export it without paying.  Self-tracking gadget vendors that make it hard to access your data are a big pet peeve of QS’ers.  It’s our data, how dare anyone try to sell it back to us or worse yet, prevent us from accessing it in a raw format.  We want to manipulate it and chart it and stroke it, etc.  Therefore, I was happy to jump through a few hoops to get my fitbit data exported to Google docs.

So physical activity is obviously important for physical health.  But more evidence is accruing that it’s important to cognitive health as well.  See, embodied cognition.  Also, there is that study that suggests your longevity is better improved by not sitting than even by exercising.  I do have a standing desk now, but I am not ready to add the treadmill to it just yet.

Since I am trying to write more, I use WordPress to tell me how many words I am writing each day.  Many writers say that the best way to improve your writing is to simply write as much as possible.   I loosely subscribe to the 10,000 hours approach to mastery as promoted by Gladwell in Outliers or Colvin in Talent Is Overrated (loosely I say.)  So it’s good to get the raw numbers: words per day.  Now I just need to a plan, a coach, feedback, and to push myself further and harder.  Ahem, moving on.

I track how many calories I’ve eaten each day using  Frankly, though, this is a tough one to keep up with.  Livestrong has a good food database and it’s fairly easy to get accurate nutritional information, but you have to manually enter each thing you eat.  The holy grail of self-tracking is the tracking that happens automatically.  There are some apps out there that help by letting you snap photos of your food to tell you how many calories it contains, but I am skeptical of the accuracy.

Calories have an obvious effect on health.  Calorie restriction and intermittent fasting are two well supported strategies for health extension.  I am especially attracted to the idea that fasting may be helpful even without calorie restriction.  However, I have always had a tendency to neglect eating (I forget to eat), so I don’t need to strive for that.  I am more interested in the idea that eating more calories might make me more productive.  When I first started tracking calories, I found that eating a breakfast with carbs and protein seemed to be correlated with more billable hours.  (Being a consultant, I have tracked this metric over the years for it’s financial benefits.)  So I wonder what the correlation will be between calories and words written.

Another metric I am trying to track is social events.  I have found that a good social event inspires me to write.  Also, I heard a speaker at QS claim a correlation between blood sugar stability and socializing with weak links (i.e. acquaintances as opposed to loved ones.)  I have often found it easier to delay meals when hanging out with acquaintances myself.  Maybe it’s a thing.

I was inspired by a guy from QS who complained that Dual N-Back cognitive training tasks were too exhausting.  They certainly are.  I did it for one-month according the to the Jaeggi protocol, but I had trouble doing it on an ongoing basis.  So I signed up for Lumosity instead which offers much shorter and more varied exercises that work on your speed, memory, attention, flexibility, and problem solving.  I track that Lumosity score as a proxy for cognitive health.  However, is a platform explicitly designed to test cognitive performance changes in response to specific interventions.  So I will try to get into that at some point.

These preceding metrics can all be collected daily (in theory.)  But I am also tracking my lab results for things like cholesterol and c-reactive protein (an inflammatory marker.)  I would like to track these more frequently, but I get queasy around needles, and Kaiser is stingy with gratuitous tests demanded by healthy people like myself.

Now crunch the numbers.

Well actually that’s a problem I hear a lot of QS’ers complain about. We gather all this data (or fail to gather it and have huge gaps as the case may be) but now what?  Many of us lack the time or statistical know-how to do a proper analysis and suss out the interesting correlations.  Luckily for me, I was asked to help demo this statistical analysis tool called Wizard for Mac at the next QS meetup.  It looks like just the thing to walk statistical neophytes like myself through a regression analysis to determine a calories eaten to words blogged correlation.

What next?

There are a number of other things I would like to track, but I haven’t gotten around to it.  Given how important heart rate variability is, and the fact that I went and got a Wahoo heart monitor and SweatBeat IOS software, I should be tracking my HRV score each morning, right?  Well, the strap IS a bit cumbersome…  Never mind, I’m doing it starting tomorrow morning, I swear.

Since reading Kurzweil’s Fantastic Voyage and Transcend on life extension, I have been supplementing irresponsibly.  I just pop a bunch of supplements and don’t really track the physiological consequences (aside from the occasional liver function test.)  Ideally, I would find a good concierge doctor (that wasn’t a quack) who would help me determine which nutrients I am actually deficient in and which supplements I might actually benefit from.  However, I am getting the sinking feeling that supplements might not be very helpful at all.  Study after study is throwing cold water on the quick-fix-by-popping-a-pill approach.  Dammit, it’s hard work to stuff your face with vegetables day and night.

Finally, I would love to track how many words I’ve read each day.  In theory, my Kindle has some of this information.  But I would probably need to embark on an epic hacking voyage to gain access to this knowledge.  I played with RescueTime for a while, which gives you in-depth analysis of your time spent online, but I got a little bugged out by the privacy implications.  I would prefer a local database.

At the end of the day, I feel that self-tracking is worthwhile for it’s own sake.  The unexamined life is not worth living.  I agree with Kevin Kelly when he says that QS helps us expand the very definition of the self.  Even if I never nail down that correlation between X and Y, I still have a better sense of who I am and what I am doing by paying attention to them.

American Gut Study on Indiegogo

If you are like me, the feast of Thanksgiving naturally calls to mind the importance of gut flora.  As I mentioned before, gut flora has received a lot of attention lately and has been implicated in many health conditions from diabetes to autism.  I myself have signed up for Melanie Swan’s gut flora study on Genomera.  This is a fairly in-depth study to track gut flora population response to probiotic intervention.  However, we are still waiting for it to attract enough participants to go forward.

If you are interested in a quick and, err, dirty way to get some basic info on your microbiome, check out this American Gut study on Indiegogo.  For as little as $99 you can have a single specimen sample analyzed and receive a report:

This PERK includes DNA extraction and 16S rRNA sequencing of one stool sample (or an oral or skin sample – the same kit works for any of these), and shows which bacteria and archaea were present in that sample along with how much of each kind. You will get a certificate suitable for framing with a readout of your microbes and a view of your microbes in the context of other people’s.

Suitable for framing?  Really?  Not even I am that out of it.

If you want to really go nuts, why not splurge and plop down $25k:

“Hundreds of genomes from your gut.”  Be among the first in the world to get the most detailed map of your gut microbiome and help us push the state-of-the-art in high-throughput sequence technology of microbial communities. We will perform ultra-deep sequencing of your microbiome sample aimed at generating as many individual bacterial genomes as possible (We can’t tell you how because the details of the technique are still under wraps prior to publication.). Includes a private consultation with project scientists to discuss the genomes with you. Only serious need inquire, please to express your interest before signing up for this one.

I am not sure what you can do with this information immediately.  It’s unlikely that your physician will be of much help unless you have some serious resources at your disposal and can afford a “concierge” doctor.  I am assuming that you will at least be able to determine which of the two primary “enterotypes” your gut flora population falls into.  From there, I imagine that you could try some interventions to improve your health.  As I mentioned in my previous article on gut flora, this article makes me skeptical that probiotic supplements will have much affect.  However, if you have been forced to take antibiotics recently, this study suggests that probiotics might reduce your risk of certain problems.  Going forward, the decreasing cost of gut flora analysis will make it easier to contrast the effects of say, sauerkraut and Jarro-Dophilus.

UPDATE 11/27/2012:

I was notified that there is yet another microbiome study on indiegogo called uBiome.  This project is similar to the American Gut study, but there are a couple of key differences.  uBiome is open to international participants, so if you aren’t a Yankee, you are still welcome.  Also, it seems to be more more longitudinally oriented (for samples taken over time.)  I for one am interested in the “Quantified uBiome” package which provides three time points and a web app to assist with experimentation.  The uBiome site seems to suggest that the microbiome can be “easily changed.”   I was initially skeptical about this, but compared to the human genome, that is probably true.  These projects will certainly help us to gain more insight into how easy it really is to domesticate your microbiota.