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.

6 thoughts on “Health Extension #11: Aging – Death by Damage vs. Death by Design

  1. I am hearing a lot of push back on this idea of programmed death, so I will definitely follow up with my friends that know about population genetics and update this post soon.

  2. A good read!
    The essay’s comment about some tension between Kenyon’s and Rebo’s approaches is provocative. If I have the flu, with one pill that strengthens my immune system, and another that weakens the offending virus, is there tension there? It seems highly likely that the anti-aging story will play out with a combination of therapies. Sure, we’d rather have our internal systems revived or sharpened to do the job, but lacking that, a few hours on the blood purifier wouldn’t be so terrible. In the health extension milieu, one often hears about piece-wise reaching “escape velocity” – repeatedly doing whatever is available to pull you through a few more years until finally you outlive the myriad of threats. I should be so lucky!

    • Walter,

      I am trying to poke gently at the SENS approach to understand why they don’t seem to have included a bullet point that addresses the idea that aging might be genetically programmed. I totally agree that short term solutions should be explored, but I am not sure if that is the explicit intention of SENS.


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