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The real takeaway from this research is that AMPK manipulation in the manner demonstrated here is categorically not an exercise mimetic because it does nothing
by reasonattlm 11y ago
The real takeaway from this research is that AMPK manipulation in the manner demonstrated here is categorically not an exercise mimetic because it does nothing in healthy individuals. A real exercise mimetic would extend median life span, since that's what exercise does in mice.
Other strategies that end up showing altered AMPK levels along the way have been shown to extend life and improve health in laboratory species. It is very complex, and researchers are very far from understanding how even very reliable and straightforward ways of slowing aging work. E.g. calorie restriction. Studied for a century, no comprehensive explanation of how it works yet.
This, along with tiny beneficial effects, is the reason we should largely ignore all of these efforts to throw drugs at metabolism in the hopes of lengthening healthspan. It is a grand waste of time, because even if wondrously successful the best you could hope for in the next few decades is something that is outperformed by actually exercising or practicing calorie restriction.
What a waste of billions of dollars that will be. Yet that's what is going to happen, judging by the willingness to fund this sort of work. It is like the research and development community has learned nothing from the outcome of fifteen years of sirtuin research.
If we want to see radical life extension in our lifetimes, it is going to come from SENS and the like, deliberate targeted efforts to repair specific aspects of biochemical damage that cause cell and tissue dysfunction. Not random drugs mined from the natural world, but elegantly engineered biotechnologies that do exactly what they are intended to do. You might look at allotopic expression of mitochondrial DNA for example, as developed by Gensight at the moment ( http://www.gensight-biologics.com/ http://www.gensight-biologics.com/ ). The problem is identified, and a precise fix applied to cells via gene therapy to make exactly the problem and only the problem go away.
That is the future of medicine. Yet the regulations and inertia behind the old drug development pipeline is very resistant to change. We'd better hope that the disruption represented by Gensight and other similar efforts takes hold, because we're going to age and suffer just like our parents and on pretty much the same schedule if it doesn't.
- skybrian 11y ago> "the best you could hope for in the next few decades is something that is outperformed by actually exercising or practicing calorie restriction" That would still be a monumental achievement (probably in the billions of dollars range) if a practical treatment came out of it. Most health costs don't come from healthy people, after all. A lot of people don't exercise and very few people practice calorie restriction. But if there is other research that would work better, then the opportunity cost is high too.
- gnoway 11y agoThis is kind of a straw man, isn't it? I realize the article leads with "exercise in a pill," but it's really about a compound that might help treat obesity and type 2 diabetes. Effect on lifespan/healthspan is only implied (via treatment of disease). Edit: you might also want to be a little more up-front about your apparent involvement with alternative avenues of research.
- reasonattlm 11y agoIt leads with exercise in a pill because AMPK manipulation is broadly expected to be a path towards an exercise mimetic. Go do some background reading on AMPK and related proteins and pathways and their effects on longevity and health in lower animals. What I find annoying about this reporting is that it is being spun as a success when by all measures it is a failure. It is a failure in exactly the same way sirtuin research was a failure, in that it only appears to produce benefits in metabolically abnormal individuals, and even then they are not high quality benefits. Meaning it isn't at all what was aimed for: the researchers have failed in even their original modest goals of slightly slowing aging by recapitulating the broad effects of exercise. Of course you can still make a profit selling very marginal treatments for type 2 diabetes to people who have that condition because they are obese and thus metabolically abnormal. This is a condition that can actually be reversed right up until very late stages by dietary restriction ( http://dx.doi.org/10.2337/db11-1835 http://dx.doi.org/10.2337/db11-1835, http://www.bbc.com/news/health-13887909 http://www.bbc.com/news/health-13887909 ), for all that few people appear to either know or be willing to act on that knowledge. The sort of therapies that might result from AMPK manipulation would be terrible in comparison to the outcome of just eating less. But that has nothing to do with making real progress in medicine. Medical research in general is so very vulnerable to disruption: you have entrenched groups producing terrible products at massive cost under heavy regulation in the midst of a revolution in the underlying technologies and plummeting costs of creating new knowledge and therapies. Something has to give.
- singulaire 11y agoIf the function of the pill is solely to mimic exercise, then it does not offer any new treatment. Obesity and diabetes can be treated just as well right now, and the treatment is exercise.
- bengarvey 11y ago"by actually exercising or practicing calorie restriction" Ever study I've read about has shown that while calorie restriction works in mice, it has no effect in humans.
- crusso 11y agoActually, calorie restriction has shown to provide life extension in every species tried so far except for one highly over-referenced rhesus monkey study that were contradicted by a later study[1]. Human study results are much more difficult to obtain due to our average life span lengths. Also there was a recent article that made it to the front page of HN talking about a positive study of intermittent fasting's longetivity-related benefits - which is probably a closely related or identical phenomenon (my guess). [1] http://www.nature.com/ncomms/2014/140401/ncomms4557/full/ncomms4557.html http://www.nature.com/ncomms/2014/140401/ncomms4557/full/nco...
- gwern 11y ago> it has no effect in humans. It certainly has documented effects on weight, blood pressure, insulin, etc. What you mean to say is that while it's been amply proven in lower species to extend lifespan, lifespan extension has not been proven in humans as of now.
- abrichr 11y agoFrom [1]: To our knowledge, only one study investigated the effects of long-term CR (with a diet of reasonable quality) on health and longevity in nonobese humans and a control group (24). This study was conducted in 120 men, of whom 60 were randomly assigned to the control group and 60 to the calorie-restricted group. The control group was fed ≈9600 kJ/d. Calorie-restricted subjects received 1 L milk and 500 g fruit every other day, which led to an overall mean energy intake of ≈6300 kJ/d (or a 35% restriction from the intake of the control group). This regimen was implemented for 3 y. Stunkard (25) reanalyzed these data and reported less time in the infirmary (123 compared with 219 d) and a nonsignificant difference in the death rate (6 compared with 13 deaths) in calorie-restricted subjects than in control subjects, respectively, which suggests that chronic CR may prolong life span in humans. [1] http://ajcn.nutrition.org/content/78/3/361.full http://ajcn.nutrition.org/content/78/3/361.full
- ItsMattyG 11y agoThere are far far more people willing to take a pill then exercise or caloric restrict. If this allows those people to survive long enough for more radical form of life extension, it could save many, many lives.
- sebastianavina 11y agothey will mix those pills with red bull and vodka at night clibs