Overweening Generalist

Saturday, March 3, 2012

Life Extension Notes

Completing the trifecta of Leary and Wilson's SMI2LE vision of a way out of technological materialism with no goal, no telos, is Life Extension. This one's a whole ungainly ball of wax, and I will have to do multiple posts on it over the coming months in order to feel like I've said anything substantial about it.

I previously posted on Space Migration HERE.
My stab at Intelligence Increase ("I" squared) was HERE.

Cellular Level
From my current view, the most exciting and radical research on life extension is the hard slog done at the level of the cell. According to some statistics, the combination of ever-faster computers and the fact that there are more scientists doing research now than at any time in history - by far! - means that key findings about how and why we age, how we can slow it down, stop it or even reverse it, are immanent. (Let us define "immanent" as something like "in the next 15 years," just for kicks, although many in the field will say that's being conservative!)

Around 1961 cytogerontologist Leonard Hayflick and his colleague Paul Moorhead defined what is now commonly called the "Hayflick Limit": they proved that cellular DNA can only replicate about 60 times during a lifetime; with constant replications, mistakes are made, gunk gets into the next generation, and accumulates over time. I heard one theorist describe it as like when you or your friends bought a Beatles record and taped it for friends. Then they taped it from the tape they were given, then those friends taped it from the taped tape, etc: after awhile you got a copy that sounded like crap. Well, when we get to be around 75, our cells are filled with gunk, the machinery has started to break down (I've seen the carburetor used as a metaphor a lot here too), and the processes that keep our hearts, brains, livers and other good stuff...rust and break. (We probably sound as bad as a washed-out Beatles tape, too.) We die. It seems we're programmed to be like that.

There are plenty of Very Bright People who think we can defeat these programs.

So far, the only proven method of extending life is to slow metabolism, which for humans means caloric restriction, or to eat less. The less food/calories, the less to metabolize, the slower gunk and noise accumulates at the cellular level. The problem with this is that it's really not very fun. I think Woody Allen put it best when he said that - I paraphrase from memory - "If you want to live to be 100, you need to give up all those things that make you want to live to be 100."

There's gotta be a better way. And it looks like there are a few prospects. I'll cover a few.

Sidelight: The literature on life extension is so extensive, it's easy to find oneself in a rocky and sedimented terminal morain. This precariousness seems heightened if the reader is a non-specialist, and who's more non-specialist than an overweening generalist? Still, I have found a few hot rocks. They seem to shimmer brilliantly. I call each one a possible fleck from the Fountain of Youth. Let us call each item a "de Leonite clue."

Here's a possible de Leonite: ELLPs. What are they? They're Extremely Long-Lasting Proteins, and they were recently found on the surface of the nucleus of a neuron by researchers at the Salk Institute's Molecular and Cell Biology Lab, led by Martin Hetzer. What's the big deal? Well, most proteins last for a few days at most. The ELLPs that coat a cell last a lifetime, and they're part of the NPC, or Nuclear Pore Complex. Okay, look at the cross-section of the cell above and note things called "microtubules," "microfilaments," and "plasma membrane." A cell needs to both protect itself from outside bad stuff and to let in outside good stuff - to put it like a nine year old. The Salk researchers found that bad stuff can happen because these ELLPs that coat the outside of the cell walls of a neuron like marble, erode over the years, and this is probably how a lot of gunk (there's our carburetor metaphor again) gets into cells. Another way of putting it: the gate keepers of the cell break down over a lifetime and allow toxins to get in, damaging DNA, and let us not even talk about the nasty stuff that happens when your DNA is damaged.

The results from this research could lead to better ways to treat or avert neurodegenerative diseases like Alzheimer's and Parkinson's. Hetzer's team were told the research they undertook would be too bold, difficult and expensive to conduct. You probably didn't hear about this in the "news" because it didn't contain enough blood, Beiber, ballgame or Beyonce.

Seriously, this is major stuff, because no one really knew ELLPs were what they were. Read more about it HERE.

Q: What are sirtuins? And what do they have to do with me?

I'm glad you asked. They are Silent Information Regulator Two proteins that act as enzymes, and were linked to life extension around 1986. Mammals have seven types of sirtuins, and Sir1 has been linked to the reason why caloric restriction works to slow aging. It gets really dodgy from here on out, for the OG.

How cool would it be if we could find something that would activate the Sir1, without having to constantly feel hungry? When we start to starve - or we restrict our caloric intake by 30%--40% - as the theory goes, some genes kick in and protect us against the stress of being hungry, and protect our cells and vital organs. These are the sirtuins. Here's where red wine comes in: it looks like, when we drink certain red wines that contain resveratrol, that it activates a gene-complex very Sir1-like, and has the same effects as caloric restriction. Instead of caloric restriction/quasi-starvation, drink a hearty glass of red zinfandel! Sound too good to be true? (Wait for it...)

 MIT professor Leonard Guarente has been at the forefront of Sir1 research, from caloric restriction to providing a theoretical platform for new anti-aging drugs based on his (and other's) sirtuin findings. Glaxo-Smith-Kline paid $720 million for a company called Sirtrus, and...here's an article from two years ago. It's not going as well as we'd/they'd hoped. In many articles, Dr. Richard Miller, a professor of Pathology at the University of Michigan and critic of the sirtuin hypothesis, has been saying that the relatively simple story of the sirtuins was too simple, that sirtuins are probably just one of very many systems in cell-signaling that influence aging. But Guarente is holding firm, recently publishing a long paper on the miraculous potentials of the sirtuins.

Meanwhile, research on the other sirtuins is hot - there's potentially gold in them thar genes! - and for the sufficiently geeky, see HERE (Sir6 linked to longer lifespan!), HERE (researchers in London seem to see a chimera in the sirtuin hunt vis a vis longevity?), and HERE, for starters. Note this last article suggests mutations that increased sirtuins were linked to anxiety and panic disorders. I think the sirtuin road led to a terminal morain for this reader. But I will still pay attention to anything that might come up. You never know what Sir5 might have in store for us, for example. The sirtuins may yet yield a dynamite de Leonite/piece of the puzzle.

I want to get into telomeres and telomerase, but first a word from an Oracle, AKA Kaku:

Stop me if you've heard this one, or just bear with me: each one of our chromosomes has a sort of "cap" of base-pairs that can be visualized like a shoelace: if you didn't have that little piece of hard plastic at the end of your laces, everything would shred and tying your shoes would be an unpleasant task. A telomere is one of these caps. It strongly appears that, with each cell division over a lifetime, the cap gets shorter. End of telomere = haywire/Hayflick Limit. Cells can't repair, eventually TAFUBAR.
Now: there are two classes of cells that don't age: your germ/sex cells (sperm/eggs, which is good, or your baby will be born looking as old as you!), and our old nemesis, the emperor of all maladies, cancer. Cancer can just go on dividing forever! It's immortal! (Not all cancer cells, just...enough. Oy. As Professor Carlin wrote in Napalm and Silly Putty, "If you live long enough, everyone you know has cancer.") Until it - cancer - kills itself by killing its host (us or our loved ones). Let's not worry about cancer's problems. It's doing just fine for now.

So what makes sex and cancer cells immortal? Telomerase. Both germ and cancer cells produce the enzyme telomerase, which keeps the telomeres intact when cells divide. Can we come up with telomerase therapy that will effectively arrest aging, or potentially reverse some of it? Dr. Michael Fossel thinks so. He thinks it's about ten years away! (Other Big Brains I've read say 50-100 years and we'll have telomerase therapy. Aubrey de Grey says about 100 years, and that guy usually seems optimistic to me. Speaking of Mr. de Grey, get a load of him if you haven't already. There are endless videos to be found if you like this one:

Axiological Level
What really interested me about what de Grey says here about those opposed to longevity research - mainstream media people who seem to regard it as faintly ridiculous or science-fiction-y and throw in the word "immortality," and gerontologists. This last I found very interesting, because de Grey seems to perceive those engaged in regenerative medicine as knowing things the gerontologists do not. Which I find totally plausible. If one reads Leonard Hayflick, one rapidly sheds any optimism for notable improvements in human lifespan soon; Hayflick is a heavyweight in the field of human lifespan studies and he's not exactly sanguine about our prospects for immortality, to put it mildly. But I wonder if de Grey is rather talking about temperaments of researchers? Just note the impression the fields have on your own disposition towards improving human lifespans: "gerontology"....""regenerative medicine"? At what point do we reconcile these two, if ever? It gets weirder.

I think it has to do with axiology, the study of our basic values. We build whole worlds of thought, political systems, ideologies, laws, and dreams on the basic building blocks of our own values. And where did we get these values that are so important to us? It's a difficult question. I've written on axiology HERE and HERE, but I have barely touched the surface of the idea.

One of the major founders of Transhumanism, Max More. Check out what he has to say between 5:26 and 8:07:

This gets to a recent book review I read in Reason magazine. I have not read The Body Politic: The Battle Over Science In America, by Jonathan D. Moreno. Not yet. Ronald Bailey's review seems to extend the values issues that Max More brought up after his famous Free Inquiry  article from 1993, between "humanists" and "transhumanists," this latter group who were enthused about More's ideas probably not even self-defining themselves as "transhumanists" at the time. Coupled with Aubrey de Grey's gerontologists vs. regenerative medicine researchers (and IT professionals, libertarians, and Canadians), now we have the "biopolitics" of strange bedfellows: biocons, who object to things like embryonic stem cell research on strictly "moral" grounds; and egalitarian leftists, who see a disaster in runaway advanced new biological techniques: only for the rich, non-egalitarian, and lacking in human dignity. In this article, "biopolitics" is defined as "the nonviolent struggle for control over the actual and imagined achievements of the new biology and the world it symbolizes."

(I analyzed Rick Santorum's views on bioethics vis a vis this wider conversation and will charitably designate him as some sort of "paleobiocon." I think I'm letting him off easy, too.)

The Reader has to decide where they stand on this stuff. Where are you, bio-ethically? The more I study this stuff, the more difficult it gets. On principle I like the idea of Unistat starting out as a country that values very highly new knowledge. And the history of the 19th/early 20th century Progressive movement and eugenics is sobering. On the other hand, I see Nassim Nicholas Taleb's book The Black Swan as prophetic (ironically!): we now live less and less in the old linear, Bell Curvey "Mediocristan" and more and more in Extremistan: the rich have gotten wildly richer and almost everyone else has stayed the same or has fallen lower. And I don't see much brightness on the horizon. Just look at the overtly bought elections. Just look at the appalling decadence in the basic fact that: the banks did what they did to our lives, got bailed out, and Obama has not been able to put in place any regulations with teeth to speak of, four years later.

However, as Taleb goes to great lengths to emphasize: we can only notice where there's risk/fragility built into a system and try to minimize it. All other bets about the future are off. No one knows. Certainly not "experts"!

I tend to be with Moreno's "bioprogressives," who welcome new advances, even if I probably won't be able to afford them. Hell, I can't even afford basic health insurance now...

Speaking of Taleb: "Don't talk about 'progress' in terms of longevity, safety, or comfort before comparing zoo animals to those in the wilderness." - p.7, Bed of Procrustes

David Jay Brown's marvelous book of interviews, Mavericks of Medicine: Conversations on the Frontiers of Medical Research (2006) was an overwhelmingly stimulating read this past week - on this subject of life extension and other topics - and is largely to blame for the gap between my last post and this one. Highly recommended! (It's dedicated to Robert Anton Wilson, too.)

To end on a lighter note, Professor Carlin thought that "Dying must have a survival value. Or it wouldn't be part of the biological process."

Ray Kurzweil - no relation to Peter Bogdanovich that I know of - on aging and supplements, for a minute and 40 seconds: "We can't rely on 'being natural,' that's not good enough..."

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