Continued Interest in Drugs that Might Slightly Slow Aging

Research institutions are willing to pour comparatively large sums into the pursuit of existing already developed and approved drugs that might, possibly, have some marginal, tiny effect on the course of degenerative aging. This is one manifestation of a large and harmful issue that plagues medical research as a whole, which is that there is very little interest in pursuing radical new improvements to the state of therapies. Rather the larger investments nowadays often go towards mining the existing catalog of approved drugs in search of different uses and slight gains that might have been overlooked in the past. Other groups delve into supplements to evade the FDA, with the similar goal of slight gains and overlooked substances. These are no paths to rapid progress or a future of greatly improved medicine.

Why is this the present state of affairs? I blame regulation. It is so enormously costly to obtain approval for any new drug, let alone a new technology that doesn't quite fall into any of the existing categories that regulators understand, that developers and researchers are steered at every step of the way towards reuse of existing drugs and other technologies. This is what you get when government influence over a field of human endeavor has risen to the point at which all that is not explicitly permitted is forbidden. Progress is greatly slowed and stifled.

Of course everyone puts on the best face for this. Look at these new and bold things we are doing, they say. They are neither new nor bold, however. Nor are they the road to greatly extended healthy lives or the defeat of aging, and those claims should be laughed out of the room when made. No existing drug such as those mentioned below can do more than slightly slow the accumulation of damage that causes aging. They don't repair that damage, they thus won't add significant numbers of years to life, and they are unlikely to even do as much good as calorie restriction or regular moderate exercise. In the case of the various drug candidates noted in the articles linked below, the evidence isn't even all that robust when it comes to extending healthy life in animal studies. This is marginal activity that will most likely do very little for the bottom line of healthy years lived. It is the business as usual of the research establishment of the yesterday, and something that must be disrupted and driven out by new and better approaches to the treatment of aging.

This is all made doubly frustrating by the fact that now, as a result of more than a decade of hard work and advocacy for aging research, many more researchers are willing to speak openly about treating aging as a medical condition. Yet they focus on strategic options for research and development that haven't much of a hope of producing meaningful gains in healthy life span. We are in the midst of a revolution in the capabilities of medical biotechnology: this is not a time to cling to past incrementalism, but rather a time to embrace new approaches and new strategies that could achieve rejuvenation and radical life extension.

Scientists' New Goal: Growing Old Without Disease

Some of the top researchers on aging in the country are trying to get an unusual clinical trial up and running. They want to test a pill that could prevent or delay some of the most debilitating diseases of old age, including Alzheimer's and cardiovascular disease. The focus of the project isn't to prolong life, although that could occur, but to make the last years or decades of people's lives more fulfilling by postponing the onset of many chronic diseases until closer to death.

Researchers expect to enroll more than 1,000 elderly participants in the randomized, controlled clinical trial to be conducted at multiple research centers and take five to seven years. The trial aims to test the drug metformin, a common medication often used to treat Type 2 diabetes, and see if it can delay or prevent other chronic diseases. (The project is being called Targeting/Taming Aging With Metformin, or TAME.) Metformin isn't necessarily more promising than other drugs that have shown signs of extending life and reducing age-related chronic diseases. But metformin has been widely and safely used for more than 60 years, has very few side effects and is inexpensive.

The scientists say that if TAME is a well-designed, large-scale study, the Food and Drug Administration might be persuaded to consider aging as an indication, or preventable condition, a move that could spur drug makers to target factors that contribute to aging. Fighting each major disease of old age separately isn't winnable. "We lower the risk of heart disease, somebody lives long enough to get cancer. If we reduce the risk of cancer, somebody lives long enough to get Alzheimer's disease." "We are suggesting that the time has arrived to attack them all by going after the biological process of aging."

An FDA spokeswoman, said the agency's perspective has long been that "aging" isn't a disease. "We clearly have approved drugs that treat consequences of aging," she said. Although the FDA currently is inclined to treat diseases prevalent in older people as separate medical conditions, "if someone in the drug-development industry found something that treated all of these, we might revisit our thinking."

Beyond Resveratrol: The Anti-Aging NAD Fad

NAD is a linchpin of energy metabolism, among other roles, and its diminishing level with age has been implicated in mitochondrial deterioration. Supplements containing nicotinamide riboside, or NR, a precursor to NAD that's found in trace amounts in milk, might be able to boost NAD levels. In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

The NAD story took off toward the end of 2013 with a high-profile paper by Harvard's David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

NMN isn't available as a consumer product. But Sinclair's report sparked excitement about NR, which was already on the market as a supplement called Niagen. In early February, Elysium Health, a startup cofounded by Sinclair's former mentor, MIT biologist Lenny Guarente, jumped into the NAD game by unveiling another supplement with NR.

This intersection of the supplement marketplace and scientific research is a sideshow and has little to do with any serious efforts that might produce treatments for the causes of aging. It will no doubt be successful in parting fools and their money, however. This sort of thing usually is, even absent a bevy of scientists willing to put their reputations on the line. Remember than nothing of any practical use came of resveratrol and sirtuin research, though it certainly generated a lot of data and new understanding of that small slice of human metabolism. Similarly nothing of practical use will emerge here. Don't fall for the hype, and don't spend time and effort advocating for or supporting efforts that cannot possibly produce meaningful gains in human life span.


I feel like the metabolic approach will change if SENS is ever able to effectively reverse aging and extend the lifespan of a mouse in a meaningful way. Until then, this is probably going to be the way forward unfortunately.

Posted by: Ham at March 18th, 2015 12:57 AM

Antonio, please cut the crap. Did you actually read the Mayo study? They use two citations to confirm the hypothesis that drug regulation and cost are not the problem. One citation leads to a site called, which claims that all the high cost studies are wrong because they are biased, an argument that can easily be used on naturalnews as well. They don't give any number on how high drug costs really are and they mainly critize a study from 2003. The second ciations leads to a paper by Light et al. 2011, which has been refuted by Tufts (

I can give you the links but costs for one patient per drug trial amount to around 100.000 USD. So if you want to approve a drug for breast cancer, you will need to recruite around 5.000 patients which amounts to 500 million USD just for the trials(!). However, only 1 in 10 drugs makes it to approval, so by taking into account the dropouts, 2.6 billion dollars for drug development per approved drug are much more reasonable (

Therefore I fully agree with Reason. Regulation is the problem. Even if drug costs only are around 100 million, no scientist can afford this. I've been working in drug development regulation for several years now and in my experience there is no field which is more innovation hostile. Remember 23andMe, they offer around 1 million SNPs for 99 USD. Paying for the traits in the normal reimbursement field would cost you way over 10,000 USD. But the FDA stepped in and only allows raw data to be sold now.

In the end, there is no free market in the medical field and regarding this statement I agree with Kantarjian et al. 2015 (Mayo). Get regulation out of the way and let scientists do their thing and let patients and doctors decide what drugs they try and what not. It is outrageous that an end-stage cancer patient is not allowed to try new innovative drugs, just because the FDA does not approve them. Does anyone evaluate how many patients die because they are not allowed access to non-FDA drugs? I bet not.

Posted by: Waverunner at March 18th, 2015 4:50 AM


I didn't read the full paper, it's behind a paywall.

Anyway, cancer drug prices are much higher than what inflation and efficacy justifies: Regulation hasn't changed that much to account for that increase in prices, and research technology is much cheaper than in the past.

Posted by: Antonio at March 18th, 2015 5:38 AM

It seems that some scientists are pushing ahead and bypassing red tape.

Bioviva for example is offering Telomerase and combined Myostatin gene therapy in South America outside of FDA climes.

I imagine a fair few other scientists will do the same unless things in the regulatory body changes to help facilitate faster research. Safety is of course paramount but progress is being held back by the current situation.

Posted by: Steve at March 18th, 2015 9:13 AM

Here's the full text, no paywall:

Waverunner's right- the article does, in fact, link to Natural News. Which is pretty much a marker saying "Do not take this seriously" if you've ever actually seen the homepage of Natural News. It's not just pseudoscience, it's the aggressive, vicious kind of "Don't vaccinate your children, GMOs are evil" brain rot pseudoscience.

Waverunner, do you have any explanation as to why it costs $100,000 per person to conduct a clinical trial? Don't just say "regulation", regulation only stipulates the number of people and the kind of studies, that's not an explanation as to why it costs a hundred f-ing thousand dollars per person to do a trial.

Also, I don't trust BioViva. Not even a little bit. Not with that sparse and uninformative of a website, not when they can't even get compliment and complement right, and definitely not when they claim without any evidence that they can use telomerase to treat AD. This isn't information, it's a facade.

Meanwhile, these scientists are trying to remove senescent-cell chemicals (instead of focusing on getting rid of the cells) and trying to attack "the biological process of aging" as if that were a sane endpoint. What the hell? Do these people really believe that aging is a single thing? (Does anyone here?!) An excess of senescent cells, gradual genetic mutations, a lack of stem cells, joint problems that can't heal, a breakdown of things like the blood-brain barrier and atherosclerosis- THESE are the conditions that characterize aging, and many of them originate from unrelated issues. There is no, and cannot possibly be, a single condition called "aging" that can be cured. It has to be done piecemeal. It cannot be done all at once.

It's human stupidity and greed that are going to do us in. Like usual.

Posted by: Slicer at March 18th, 2015 10:16 AM

Slicer, do you know where I have the 100.000 USD claim from? It was Kantarjian et al. 2013. ROFL, I really had no idea, that he authored this paper.

In my eyes most of their arguments are directed at regulation and against FDA intervention but see for yourself:

Page 3, left column, near the end.

Posted by: Waverunner at March 18th, 2015 12:40 PM

The pure greed of drug companies seems to play a big part in that linked paper as well (pay for delay is just pure evil). I'd love to know what that QTc business is about.

I'm not doubting that your number is accurate, I'm asking where, exactly, the money goes. People can say all day long that "it's regulation" but that's an excuse, not an explanation, and even that paper doesn't go into detail. Again, where exactly is the 100,000 dollars per person going?

Somebody needs to explain to the general public, in detail, what the hell is going on here.

Posted by: Slicer at March 18th, 2015 1:23 PM

I don't know where the 100.000 dollars are created exactly. The QTc industry is one example: "An example of such waste is the emerging QTc industry which monitors QTc prolongations related to novel agents. In the cancer setting, this has contributed to redundant infrastructures and excessive work and expenses, without any protection for patients."

More surveillance equals more cost. The Manhattan Institute had a report about the costs of Phase III trials but it's not directly related to the 100,000 dollar number. Table 1 gives a good impression of where some of the cost increases come from. Interestingly, this was just from 1999 to 2005:

Posted by: Waverunner at March 18th, 2015 1:41 PM

Steves, thanks for the link, very interesting. In my eyes, going abroad and leaving FDA regulation is the only way to foster true innovation in the healthcare field.

Posted by: Waverunner at March 18th, 2015 1:44 PM

That's ideology, not explanation, and the guy publishing that is a committed ideologue.

He thoroughly cherry-picks the drug classes he talks about and starts with two anti-obesity drugs, both of which accomplish next to nothing efficacy-wise and are for people who find paying however much money for drugs less of a hurdle than summoning up the willpower to put down a fork.

And then there's this:

"the company had no way to know that Taspoglutide would prove to be less effective than already available pharmaceuticals. When Phase III trials showed that to be the case, the company lost its entire investment in the diabetes field."

Boo hoo! You couldn't make money selling a less effective drug to people! How horrible! Nanotechnology hasn't developed the violin I'd need here.

Posted by: Slicer at March 18th, 2015 2:07 PM

You might take a look at:

It's getting dated in some aspects now, but represents a fairly pro-regulatory view. It doesn't go anywhere near far enough from my point of view, and is generally far too mild, but it is a useful thing to show to people who think that the FDA or something much like it should exist.

Posted by: Reason at March 18th, 2015 2:54 PM

Same deal with building nuclear reactors...where does 10 billion USD disappear to build a reactor?

Posted by: rdg at March 18th, 2015 9:05 PM

Slicer, don't take it personally but you really are a big joke. I keep giving you the links to answer your questions but either you don't read them or you don't comprehend them. Instead you claim others to be ideologues, while you seem to be a huge ideologue yourself. You ask where the 100.000 dollars come from and I try to supply you with sources but instead of looking at table 1, you don't lose one word on it but you bring up all your new crap. Internet discussions are a huge waste of time. I've learned that one now, thanks.

"He thoroughly cherry-picks the drug classes he talks about." Says who, you? Obesity, diabetes, heart disease and orphan drugs are cherry-picked?

"two anti-obesity drugs, both of which accomplish next to nothing efficacy-wise" Says who, you? 23% vs 10% is next to nothing? The problem is, effectiveness wasn't even the point of the argument, the argument was that the FDA made all kinds of claims about the safety of the drug. Did you actually read it or do you cherry-pick the arguments you like?

"and are for people who find paying however much money for drugs less of a hurdle than summoning up the willpower to put down a fork." None of your business what other people do with their money. Who do you actually think you are? Our moronic Fuhrer?

"Boo hoo! You couldn't make money selling a less effective drug to people! How horrible." Guess what, a Samsung S6 is better than a Motorola G2 but Motorla is still making money from the G2. How horrible! We should forbid Motorola to sell it's G2 smartphone.

Posted by: Waverunner at March 19th, 2015 1:56 AM

Thanks for the link, Slicer. I will read it when I have some time (I'm very busy today).

Posted by: Antonio at March 19th, 2015 6:33 AM

Whilst you may or may not think TAME = Lame is does help bring treating aging further into the mainstream and less of a percieved psudoscience. Now I agree such studies are likely not adding anything significant lifespan wise it doors open the door for the FDA to change how it views aging. So yes I think personally such interventions are not overly useful it may change things if aging research becomes more mainstream. We have already seen aging research move from being laughed at to the realms of it could be done.

Posted by: Steve H at March 19th, 2015 8:37 AM

Oh boy, somebody got mad when an obvious ideologue was outed as an obvious ideologue! It's almost as if the guy's history involves complaining about Obamacare and he took a position with (snicker) Mitt Romney's campaign. Excuse me, I think I'm going to go link to communications from Obama staffers, maybe some people at Public Citizen or MoveOn, for some similarly non-biased data... nah, I won't.

The only conclusion he clearly comes to is "Companies should be able to sell drugs to people without knowing whether or not they work". That's the whole point of it. "We're not making enough money having to sell proven drugs to people. Let us sell unproven ones so we can recoup our costs. It's okay, you can forbid us from advertising them." (And then that would just get blown out in court by the first lawyer to bring up the First Amendment.) Not "here's the trials that aren't necessary", not "these normally performed investigations here and here don't actually need to be done and are not helpful" - rather, "please just let us skip this safety stuff."

And of course that "paper" had no mention of why the FDA might be investigating those obesity drugs specifically for heart problems; there was this little thing called phen-fen, and it's a very good bet the mechanism of action is similar.

The only piece of real information in the entire thing involving rising costs is Table 1 and it's notably sparse. In fact, nothing in that mess mentions the current $100,000 figure at all.

Meanwhile, from the people who actually did the Tufts study... (This is quite a bit of the information I was looking for, but a letter shows that they just can't dig deep enough to get the rest)

"Lengthening development and approval times were not responsible for driving up development costs, according to DiMasi."


In fact, more than half of the 100,000-per-person figure isn't actually even spent money; it's "time costs", which is the money the investors could be making but aren't.

The actual numbers to this stuff (where the money is *really going*) appear to be out there- but they're being sold on a WordPress blog for three and a half thousand dollars for one subset...

Posted by: Slicer at March 19th, 2015 9:48 AM

*not more than half, slightly less than half

Posted by: Slicer at March 19th, 2015 9:50 AM
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