Samstag, 28. September 2013

Planetary boundaries: Basic Ecology for the Biogerontologist

Everyone who cares about healthy life extension should also have a basic understanding and an interest in planetary scale ecology. Our future must be sustainable or there is no future, that much we know.

A few papers on this topic:

Nature. 2009 Sep 24;461(7263):472-5. doi: 10.1038/461472a.
A safe operating space for humanity.
Rockström J, Steffen W, Noone K, Persson A, Chapin FS 3rd, Lambin EF, Lenton TM, Scheffer M, Folke C, Schellnhuber HJ, Nykvist B, de Wit CA, Hughes T, van der Leeuw S, Rodhe H, Sörlin S, Snyder PK, Costanza R, Svedin U, Falkenmark M, Karlberg L, Corell RW, Fabry VJ, Hansen J, Walker B, Liverman D, Richardson K, Crutzen P, Foley JA.

Rockström, Johan, et al. "Planetary boundaries: exploring the safe operating space for humanity." Ecology and society 14.2 (2009).
http://www.ecologyandsociety.org/vol14/iss2/art32/

Science. 2012 Sep 21;337(6101):1458-9.
Ecology. A measurable planetary boundary for the biosphere.
Running SW.

Montag, 16. September 2013

What can you do to help? Crowdfunding!

See here for a project summary.

I am a little mouse and I want to live longer!
Life is precious. Health too. This is why communities of researchers and citizens dedicate our lives to discover new ways to gain additional years of healthy life.
As research progresses, more and more compounds are believed to be good to maintain health over long periods of time. But wouldn't that take decades of clinical trials to verify it? A key step is to do such a clinical trial... in mice : that is what we call a mouse lifespan test. Mouse lifespan tests are infrequent because of their length, their costs and the required environments; but it is crucially needed to continue adding years of healthy life.
Here, we step on the shoulders of giants : by contributing you can help us test a combination of drugs shown to extend healthy lifespan in mice. The largest life extension in mice so far resulted from a similar effort, where one mouse lived very close to 5 years (mice usually live 2-3 years)! The result should be key to to optimally search for additional years of healthy life.

Pros:
Indirectly supported by the SENS Foundation -therefore tax-deductible in the USA, large enough sample size, rational polypill approach. And I assume that they will not make any obvious mistakes if they are advised by Stephen Spindler.

Cons:
Funding fees of 4-9% (overhead). EDIT: Now I have found the correct number for non-profit fund raisers: "nonprofit are automatically granted a 25% discount on our platform fees..."

Questions:
Animal husbandry? SPF/Hygienic Conditions? Lifespans of historical controls? What approach will be taken to exclude crypto-CR/weight-loss?

Overall, the project seems legit and methodologically sound, but I have only briefly reviewed the issue. I will try to follow the story as it develops.

Dienstag, 3. September 2013

Set up to fail: are scientists stupid?

Now that I have your attention, I am going to very briefly review several recent papers relevant to calorie restriction research.

Time and again so called studies of “calorie restriction” (CR) have failed to implement well-designed restriction, randomizing overweight subjects instead, making them no different from the thousands of weight-loss studies. But if we ever want to confirm or refute the efficacy of CR we need high quality data. Alas, rarely do we get such data. So, always remember that CR must be implemented in lean and healthy animals & humans.

Unsurprisingly, the CALERIE study did it again (1, 2). That is, failing to randomize lean people. They already once messed this up with their phase 1 pilot study, which was forgivable. At least we are getting close at a BMI of 25.1 (23.8, 26.4) and n=220, but it's not good enough. There are two reasons for this failure:


1. Americans are getting heavier and heavier and it is hard to find lean people,

1a. Therefore the maximum BMI they allowed was 28 , clearly overweight by most criteria, 
2. They excluded volunteers below a BMI of 22.

Their excuse for the latter is flimsy (2):

“The lower BMI limit was selected primarily for safety reasons. That is, the commonly used standard of underweight is BMI less than or equal to 18.5 kg/m2, and the lower limit provides an adequate buffer from this threshold as participants lose weight over the 2-year intervention.”

Oh my, oh my. And they do not even give a reference. I wonder why? Sarcasm aside, the reason is obvious, since the 18.5 BMI-cutoff is arbitrary. If you trust the epidemiology anything below some 22-25 is unhealthy (3). If you include other strands of evidence, i.e. controlled trials in animals including primates, short term trials in humans and (arguably, weaker, “cross-sectional”) epidemiology (see ref. 4. for a brief review) you must admit that we simply do not know and that the optimum might as well be at very low BMIs or rather very low calorie intakes.

Why then does a study trying to test whether low calorie diets are safe and healthy assume the conclusion that they are not?