You Have To Do Better Than That

The trouble with research and development in biotechnology and applied life science knowledge is that it's ridiculously complicated. Here I am, ten years into the forest as an observer of one small part of the field, and its taken me this long to figure out how not to walk into the biggest trees or otherwise make a fool of myself. I'm still woefully underinformed compared to synthesist researchers, and I've paid close attention to but a fraction of what's going on out there. It's broad, ever-changing, and hard.

Now consider this: in any rapidly changing field or research there are facts and there are claims, where a "fact" is just a claim with very solid backing. It can be difficult for an observer, such as a journalist, say, to tell the difference between facts and claims. You interview some guy, or you're reading a few popular reviews, and they present a variety of information. Some are good, some are bad, some have an agenda to push, and others are just wrong. Being published in a complex field is not a guarantee of correctness or of support for your thesis. If you're a journalist writing to a deadline for the normal pittance, and for an audience who know even less about the field than you do on average, then why take the effort needed to pick out fact from claim? It just doesn't pay anything back to your bottom line.

This economic picture is why most popular publications on science are riddled with errors. They don't try to distinguish between fact and claim save where it's glaringly obvious, don't need to do so to in order to make money, and even an 80/20 effort would probably be prohibitively expensive for the return on investment.

What prompted this line of thought was a recent online piece at h+ Magazine on life span, antioxidants, and in particular the antioxidant superoxide dismutase (SOD) that is generated in various forms within the body. Frankly the piece is a mess, and a very good example of the false impression of a field you can end up with when you don't take the time pick apart fact from claim.

The short version of my commentary here is that you, the reader, should take the implied conclusion of the piece - manipulating SOD by means of pharmaceuticals is important to future engineered human longevity - as falling somewhere in that nebulous space between a lie, a red herring, a big unknown, and an unlikely outcome. More detail is in the following points

  • The article paints SOD as important to longevity. There is by no means a weight of evidence linking increased SOD with increased longevity between species, however, or even within a species. If you even superficially survey the literature you'll find examples of varied forms of SOD overexpression, underexpression, and deletion moving life span in either direction under various circumstances.

  • The author further claims:

    "In humans and other mammals antioxidant enzyme levels normally decline with age and levels of inflammatory gene expression, like COX-2 and IL6, increase with age. ... drugs or supplements that create the effects of keeping S.O.D. and other antioxidant levels at youthful or higher levels are the only alternative [to calorie restriction] to these inevitable 'programmed' aspects of the aging process."

    Now to start with, a brief survey of the literature tells us that natural antioxidant levels do not uniformly decrease with age in mammals. Some types of SOD increase in some tissues in response to raised levels of oxidants and oxidative damage, for example, even as other types fall or level off. But even taking what is written at face value, the conclusion is a huge leap from known correlations (i.e. calorie restriction slows aging, and thus makes pretty much every biochemical measure tried to date look like that of a younger individual) to an assumed causation (less SOD is bad), and then again to an equally assumed single course of action (drugs and supplements). I'm all for speculation, and then testing on the basis of that speculation, but this is phrased as certainty.

  • The article makes no mention of the issue of location in the cell. A cell consists of thousands of distinct components, and demonstrated extensions of healthy life span in mice via the application of additional antioxidants show that the location of those antioxidants within the cell is crucial: it has to be at the mitochondria. Every other strategy tried to date does nothing by comparison, or actually causes harm by interfering in the use of reactive oxygen species as signaling molecules.
  • The article references Protandim as "shown in a published human clinical trial to raise S.O.D. levels." This is in fact a dubious interpretation of the trial data, pushed by the manufacturer for all the obvious reasons. Protandim is an excellent example of the sort of marketing and unproven product that makes it hard for people to talk seriously about developing longevity therapies. By way of comparison, in the Skulachev laboratory, Russian researchers have demonstrated a 20-30% extension of life in mice using their engineered antioxidant compound. I think it's safe to say that if your antioxidant therapy doesn't extend healthy life in animal studies, then you don't really have anything of interest.

So in short, the article gets the basic science wrong, reads correlations as causations, misses the really interesting work that is taking place in this area of study (30% life extension through mitochondrially targeted antioxidant compounds or genetic engineering of catalase expression in mice), and points to dubious and dubiously marketed supplements as the future. There's no robust evidence for SOD supplementation, or indeed use of any presently available antioxidant supplement for longevity. On the other hand, there exists very solid evidence - in the form of mice living longer - for the Skulachev or Rabinovitch methods of using antioxidants specifically targeted to mitochondria.

So overall not a good article at all; it's pretty much disinformation. You can do better than this, h+ staff.

Comments

There is an enormous body of data accumulating since 1980 that completely refutes your claim that there is no correlation between mammalian longevity and superoxide dismutase levels. Please kindly read these references, two of which are available full text. PMID # (Pubmed number)3904717, FULL TEXT AVAILABLE FREE, Antioxidants and longevity of mammalian species. Basic Life Sciences, 1985;35:15-73.
PMID # 1985414. FULL TEXT AVAILABLE FREE. Antioxidants and aging. Am.J.Clin Nutr. 1991 Jan;5391 Suppl); 373S-379S.
Also in abstract form to you on Pubmed Home-PMID # 6840558. Superoxide dismutase, longevity and specific metabolic rate.
I appreciate your feedback letter very much. I received numerous letters of this nature when I was Research Director and Product Development Director at Life Extension Foundation. I only ask one small favor- please look up the references to the article before writing your comments. Thank you for caring to respond.

Posted by: John Colman at June 17th, 2009 11:01 AM

John, did you take the time to look at any of the links I provided above? There are, as I said, a great many papers that show all sorts of relationships between different types of SOD, aging, and life span: it's different in different species, under different life circumstances for the same species, for different varieties of SOD, and in different tissues.

You can't pick your thesis based on the fraction of papers that support you (and in biology definitely not based on ten to fifteen year old work!); you have to look at the whole field, and the recent field.

A final note: your background at the LEF well explains your favorable view of supplements as the path forward. Regular readers will know my opinions on that already - it's a waste of time in comparison to longevity dividend style metabolic engineering which is in turn a waste of time in comparison to SENS-style work.

Posted by: Reason at June 17th, 2009 11:56 AM

Excellent analysis, caution and reply Reason.

Note a similar critique that follows this self-referenced recent post elsewhere by the same crowd that reflects a troublesome pseudo science peddling pattern:

At 4:09 PM (PDT), April 28, 2009, James Clement wrote:
> Today we ran an exclusive interview with Dr. Sean Hu, CEO of > Beike Biotechnology of China. They have treated 15,000
> patients with various stem cell therapies. There article can be > read here:
>
>
> James Clement

Amazing, James, 15,000 stem cell therapy recipients, you report, and not even one credible stem cell scientist's independently verified simple pre-post meaningful difference. Indeed, nor even a 'Dr. Sean Hu' attested film of just one substantial pre-post clinical outcome. Nor, oddly enough, even a display of his vitae (the only individual listed in the "Key Personnel" section of the http://www.beikebiotech.com website), or even the names and backgrounds of just a representative sample of the "over 60 Ph.D. Researchers" who he "has focusing on stem cell research."

I could go on, but that's simply amazing enough.

DW

Posted by: auvee at June 18th, 2009 5:13 PM

THANK you. I have thought for quite a while now that overall the "h+" movement is vastly under-critical (and shooting itself in the foot by being so, as good science REQUIRES actually caring about whether something works, as opposed to whether something is capable of generating enthusiasm, and without good science, effective longevity medicine *definitely* won't happen). People need to work harder at grokking *just how complex this biogerontology stuff actually is* -- not that it's impossible to understand of course, but that it takes more than just reading a few press releases here and there, and that as an emerging science one has to be careful not to get over-attached to one exciting-sounding thing as "the answer".

Posted by: AnneC at June 21st, 2009 12:19 AM

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