Samstag, 25. Mai 2013

Recommended reading: CR, growth hormones

I will try to comment on both these research areas in the future.

CR in Nonhuman Primates: A Muddle for Monkeys, Men, and Mimetics
(for the advanced reader)
Calorie restriction (CR) is the most well-characterized and arguably the most robust intervention into the degenerative aging process in experimental animals. Biomedical gerontologists have therefore proposed "CR mimetics" — pharmacological modulators of the signaling pathways underlying the age-retarding effects of CR — as a route to the development of interventions against the diseases and disabilities of aging. The viability of this strategy necessarily depends upon the human translatability of CR. Lifespan studies in human CR being impracticable, studies in longevous nonhuman primates were initiated at the Wisconsin National Primate Research Center (WNPRC) and at the National Institute on Aging (NIA) to give strong surrogate evidence on the issue. Disconcertingly, the two studies have come to opposing outcomes, with CR extending life relative to controls at WNPRC and not doing so at NIA. This article explores several possible interpretations of the discrepancy, focusing on two with the greatest explanatory power. Both interpretations begin from the premise that the WNPRC control animals were overfed, and that the "CR" animals in that study — as well as the control animals at NIA — were healthier by comparison for the trivial reason that they were not suffering the metabolic consequences of obesity. In the "diminishing returns" hypothesis, there was no increase in lifespan in NIA CR animals relative to nonobese controls because there is nothing to be gained from reducing food intake beyond what is needed to remain reasonably lean; thus, CR is not translatable to human or nonhuman primates, and CR mimetics cannot even in principle be created. In the "dose-response" hypothesis, the NIA's null result is interpreted as resulting from an inadequate and progressively declining degree of CR relative to the healthy baseline of the ad libitum group; this interpretation is supported with data on food motivation, body composition, and the metabolic responses to CR, and with reference to the effects of CR on the latter parameters in laboratory rodents and in humans. While the "dose-response" hypothesis holds out hope for the human translatability of CR (and thus, the theoretical possibility of true CR mimetics), there remain inherent and likely insurmountable barriers to the development of CR mimetics as effective interventions for human use, and thus researchers are urged to redirect their efforts toward rejuvenation biotechnology for the rapid and maximally effective development of new therapies to prevent and cure the diseases and disabilities of aging.

Here, a very understandable and concise review on growth hormones and aging:
A recent report of virtually complete protection from diabetes and cancer in a population of people with hereditary dwarfism revived interest in elucidating the relationships between growth, adult body size, age-related disease and longevity. In many species, smaller individuals outlive those that are larger and a similar relationship was shown in studies of various human populations. Adult body size is strongly dependent on the actions of growth hormone (GH) and the absence of GH or GH receptor in mice leads to a remarkable extension of longevity. Many mechanisms that may account for, or contribute to, this association have been identified. It is suggested that modest modifications of the diet at different ages may extend human healthspan and lifespan by reducing levels of hormones that stimulate growth.
Gerontology. 2012;58(4):337-43. doi: 10.1159/000335166. Epub 2012 Jan 18.
Healthy aging: is smaller better? - a mini-review. Bartke A.

Donnerstag, 16. Mai 2013

Oy vey! Fish oil fails AGAIN

N Engl J Med. 2013 May 9;368(19):1800-8. doi: 10.1056/NEJMoa1205409.
n-3 fatty acids in patients with multiple cardiovascular risk factors.
Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, Longoni P, Marzona I, Milani V, Silletta MG, Tognoni G, Marchioli R.

BACKGROUND: Trials have shown a beneficial effect of n-3 polyunsaturated fatty acids in patients with a previous myocardial infarction or heart failure. We evaluated the potential benefit of such therapy in patients with multiple cardiovascular risk factors or atherosclerotic vascular disease who had not had a myocardial infarction. [=primary prevention]
METHODS: In this double-blind, placebo-controlled clinical trial, we enrolled a cohort of patients who were followed by a network of 860 general practitioners in Italy. Eligible patients were men and women with multiple cardiovascular risk factors or atherosclerotic vascular disease but not myocardial infarction. Patients were randomly assigned to n-3 fatty acids (1 g daily) or placebo (olive oil). The initially specified primary end point was the cumulative rate of death, nonfatal myocardial infarction, and nonfatal stroke. At 1 year, after the event rate was found to be lower than anticipated, the primary end point was revised as time to death from cardiovascular causes or admission to the hospital for cardiovascular causes.
RESULTS: Of the 12,513 patients enrolled, 6244 were randomly assigned to n-3 fatty acids and 6269 to placebo. With a median of 5 years of follow-up, the primary end point occurred in 1478 of 12,505 patients included in the analysis (11.8%), of whom 733 of 6239 (11.7%) had received n-3 fatty acids and 745 of 6266 (11.9%) had received placebo (adjusted hazard ratio with n-3 fatty acids, 0.97; 95% confidence interval, 0.88 to 1.08; P=0.58). The same null results were observed for all the secondary end points.
CONCLUSIONS: In a large general-practice cohort of patients with multiple cardiovascular risk factors, daily treatment with n-3 fatty acids did not reduce cardiovascular mortality and morbidity. (Funded by Società Prodotti Antibiotici and others; number, NCT00317707.).
A reminder:
Arch Intern Med. 2012 May 14;172(9):686-94. doi: 10.1001/archinternmed.2012.262.
Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials.
Kwak SM, Myung SK, Lee YJ, Seo HG; Korean Meta-analysis Study Group.

"Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease."

The Good: 
Other large studies are ongoing e.g. VITamin D and OmegA-3 TriaL (VITAL). If there is an effect we may be able to tease it out, but I doubt it at this point.

Freitag, 3. Mai 2013

"DEFCON 20 - Hacking Humanity: Human Augmentation and You" (video)

Here are my notes & comments:
  • it's a DEF CON 2012 talk: light-hearted fun combined with more serious ideas
  • I am feeling nostalgic since I used to be very interested in hacking.
  • I noticed that hackers are still sexist/use sexist language
  • All sorts of medical devices to mitigate health problems exist, from cardiac pacemakers to cochlear implants. In that sense, human enhancement has existed for decades or centuries. Subdermal implants are relatively advanced and it would be nice if they could run on endogenous glucose (already done in the lab).
    However, medical devices are always usually inferior to the real deal. Oscar Pistorius' leg prosthetics may trump flesh and bone.
  • What are the ethics of prosthetics if they are better than their natural counterparts? In the most brutal and simplified case: yes, people will cut off their limbs to gain an edge in sports.
  • nootropics, etc.
  • mainstreaming of this concept is important
  • early technology, implants can be very dangerous (RFID chips caused sarcomas according to the video)
  • They recommend "humanity plus" and the "singularity institute" but left out and; I am not very familiar with the first two and cannot vouch for them. The problem is there are serious thinkers considering human enhancement, but also embarrassing figures like Ray Kurzweil.

Offtopic: The Pistorius Ban
I have NOT followed this in detail, so take my reasoning with a grain of salt. I have wondered about the ethics involved since I read about this case. So why do I believe the ban was wrong and damaging to human augmentation?
How do you become a top athlete? You do it by training (internal factor) and by winning the genetic lottery (external factors like biomechanics). Since the latter is neither just nor takes any skill, it is something we would like to avoid. This is the concept of equal opportunity. While doping, for instance, may act as an equalizer* consistent with "equal opportunity", it violates another principle: safety & free choice. If doping were legal athletes would feel pressured to risk their lives to perform well, even more so than they do now.

In contrast supplementation with creatine and caffeine is entirely "unnatural", probably effective in several sports, equalizing* and tournament legal because it is safe.

I fail to see how consciously choosing artificial limbs with superior biomechanics is more unethical than winning the genetic lottery and choosing the right parents.
Every athlete who can safely increase their performance should be allowed to do so. (That is why amputation could be considered doping in this case.)

*it has been speculated that doping disproportionately helps those with lower performance