$54,000
$19,257

"So Does Ibuprofen"

Every few years a new hot thing emerges in the field of drug candidates to slow aging. It was sirtuins for a while and then rapamycin and there will be others in due course. This happens because it is very possible to raise funding, start a company, and make a lot of money from this sort of thing even if - as is always the case to date - nothing of significance ever comes of it in terms of treatments that can actually extend life. As I've said in the past, this all seems like a really great cover story for the real scientific goal of amassing detailed data on the operation of cellular metabolism. The stated goals of slowing aging serve to draw in investment that would otherwise be hard to find at the needed levels: metabolism is ferociously complex, and trying to map it is chewing up billions of dollars. This is work that should be done, and the faster the better, but I think it disingenuous to talk of any real possibility that significant human life extension can result from it in the next few decades.

For real progress in treating aging an entirely different direction in scientific strategy is needed. Not mining the natural world for drug candidates that might slow down aging in poorly understood ways by altering poorly understood metabolic mechanisms, but rather deliberately aimed efforts to repair the known and comparatively well understood forms of damage that cause aging. We can bypass the need for a full and detailed understanding of how this damage interacts with every part of our metabolism to cause aging by taking the well validated and time-proven list of fundamental differences between old tissue and young tissue - a list of forms of cellular and molecular damage - and then repairing those differences. There is even a detailed set of research plans leading to treatments that can achieve this goal, which is a very large departure from the world of slowing aging through metabolic manipulation, where there is no plan to speak of and nowhere near enough knowledge to create one.

This is not even to mention the fact that slowing down damage accumulation can never be as good as repairing damage in terms of benefits delivered, and slowing further damage can do very little for old people who are already very damaged. The old need repair, and repair as a strategy is simply better overall in any case. It continues to amaze me that the clearly far worse, far more expensive, far less understood approach to treating aging is the one that dominates in this small research community.

In any case, every time a new overhyped drug candidate to slow aging emerges people get excited about it. Short memories, if you ask me. But the next time that someone you know in the community becomes fired up about early stage development of an age-slowing drug candidate that extends life in animal studies you can offer some needed perspective by saying "but so does ibuprofen." And what does ibuprofen do for life span in humans? Nothing meaningful enough to show up in five decades of trials, studies, and worldwide usage.

Ibuprofen Use Leads to Extended Lifespan in Several Species, Study Shows

"We first used baker's yeast, which is an established aging model, and noticed that the yeast treated with ibuprofen lived longer. Then we tried the same process with worms and flies and saw the same extended lifespan. Plus, these organisms not only lived longer, but also appeared healthy." The treatment, given at doses comparable to the recommended human dose, added about 15 percent more to the species lives. In humans, that would be equivalent to another dozen or so years of healthy living.

The three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan, an amino acid found in every cell of every organism. Tryptophan is essential for humans, who get it from protein sources in the diet. "We are not sure why this works, but it's worth exploring further. This study was a proof of principle to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms. Therefore, it should be possible to find others like ibuprofen with even better ability to extend lifespan, with the aim of adding healthy years of life in people."

Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

Aging is the greatest risk factor for many diseases, which together account for the majority of global deaths and healthcare costs. Here we show that the common drug ibuprofen increases the lifespan of yeast, worms and flies, indicative of conserved longevity effects. In budding yeast, an excellent model of cellular longevity mechanisms, ibuprofen's pro-longevity action is independent of its known anti-inflammatory role. We show that the critical function of ibuprofen in longevity is to inhibit the uptake of aromatic amino acids, by destabilizing the high-affinity tryptophan permease. We further show that ibuprofen alters cell cycle progression. Mirroring the effects of ibuprofen, we found that most yeast long-lived mutants were also similarly affected in cell cycle progression. These findings identify a safe drug that extends the lifespan of divergent organisms and reveal fundamental cellular properties associated with longevity.

The goal of taking decades and billions to add just a few years to adult life expectancy doesn't fill me with glee. If that much time and money are to be expended, and I am to become old waiting, I want far better expected outcomes for success: decades of healthy life and rejuvenation, not pills to very slightly slow down the remaining decline. Fund research into repair biotechnologies after the SENS model, not the same old drug development programs that gave us a better knowledge of sirtuins and little else.

Comments

The problem with ibuprofen is that continuous use causes liver damage. Liver damage is a problem with all of the non-aspirin (ibuprofen, Tylenol, advil, etc.) pain relievers.

Posted by: Abelard Lindsey at December 18th, 2014 5:21 PM

All of these can affect the liver, including aspirin.

But regarding NSAIDs: Advil (ibuprofen) mostly affects the kidneys. Tylenol (acetaminophen) mostly affects the liver. Aleve (naproxen) I believe mostly affects the stomach.

Posted by: John at December 19th, 2014 11:53 AM

@ Reason - better use your energy on trying to raise funds for SENS, rather than create a polemic around subject like this. Have a constructive approach, these kind of studies will be done regardless. Even they weren't done, unfortunately those funds will never reach SENS.
However, if such thing indeed works - you never know - will help some people/pets reach "escape velocity". So this isn't bad at all. Looking at the data behind it, some conclusions can be drawn, and researchers (like SENS) can avoid pathways that leads to nothing, or can plug in some meaningful data in their research. There is some data, that can be useful in a way. Again, look from a different perspective, do not approach it at low level logic, that won't get you anywhere good on this subject.

In any case, even SENS has to come up with something real on the market, so people will start believing (and donating more) that rejuvenation is actually possible. Because as of now, SENS do not have anything proven, not even a "ibuprofen" type of thing.

So we should better focus on raising more funds for them, and keep reminding them to put something on real world. They have an opportunity window of 1-3 years, after that people will lose faith, and if they will not generate real results the momentum will be lost. And that will be really bad for rejuvenation community.

Posted by: Adrian Crisan at December 19th, 2014 6:39 PM

On one hand stories like this now wind me up (since I started reading the Fightaging blog) as it will lead to money being thrown away on something that will make no difference to life or healthspans in humans (but may give some data on metabolism).

On the other hand they cheer me. If big Pharma is prepared to pump $720 million into a SIRT1 drug with known large risks of failure, then once one or more of the SENS proposed therapies get their technological proof of concept demonstrations, it shouldn't be too hard to raise money after that surely?

Posted by: Jim at December 20th, 2014 11:18 AM

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