The Nutraceutical Strategy in Attempts to Slow Aging

There is a greater fool at the end of many paths of research and development, the wallet or collection of wallets that indirectly bankrolls the work. Early for-profit investment occurs because investors believe they can sell their stake at a higher price down the line. Other reasons exist, such as the desire to do good in the world, but are entirely secondary. Most investors, and certainly the wealthier ones, have a fiduciary duty to turn away from world-saving in favor of making money. The market for early for-profit investment in turn indirectly steers research interests and the ability to raise funds from other sources: whatever is presently hot is much more likely to receive grants and philanthropic sponsorship. The state of the market at the end of the development process thus reaches back to influence every part of the long chain of research and development. The predicted inclinations of the greater fool are the tail that wags the dog.

The greater fool of interest for this post is the one indirectly funding the ongoing construction of a grand catalog of human metabolism, an exhaustive accounting of the fine details of how our cellular biochemistry operates and ages. This is understood in outline, but beneath that outline lies an enormous unexplored space of protein interactions, causes and consequences, and the relationship of various states in the system to health at every level. The greater fool is told by various parties that the goal is to enhance healthy longevity, but that isn't really happening via these explorations of metabolism, and in truth doesn't have much of a hope of happening via this research strategy. Look at the past fifteen years of sirtuin research in connection with the calorie restriction response, wherein the greater fool was - collectively - the GlaxoSmithKline shareholder community following the Sirtris acquisition. Well-managed hype sputtered out quite quickly after that liquidity event into nothing more than a slightly greater understanding of a few very narrow areas of mammalian biochemistry. This process happens over and again for each new potential calorie restriction mimetic, or other methodology claimed to slow the progress of aging by altering the operation of metabolism. Yet there is always a greater fool willing to buy.

Even if a drug was developed to completely mimic the beneficial effects of calorie restriction, so what? That is a convenience device, no more. Those practicing calorie restriction have somewhat better health and somewhat less age-related disease, and might live as many as five years longer. It's a larger effect than any currently available medical technology can provide. Nonetheless, the large majority of those people do not and will not live to see 90 years of age in the environment of today's medical technology. They still live the last years of their lives in frailty and pain. Why spend billions on striving to create a convenience device to recreate some of this marginal effect, tiny in the grand scheme of things? Because some people can get rich doing it.

The recent history of medical development related to slowing aging is that some folk have found they can do very well thank you by promising the prospect of enhanced longevity, while delivering nothing of value beyond scientific knowledge. In different circumstances I might be inclined to praise this as a great hack on investment community culture: direct more funding into life science research rather than cat pictures on the internet, and take a deserved cut as the individual who manages to make that happen. There are certainly far worse things for the greater fool to be talked into doing with his or her money.

Today, however, this business of making hay while the sun shines, based on ways to slightly slow aging largely emerged from calorie restriction research, is a distraction from the prospect of real progress. Messing with metabolism in this way cannot even in principle produce meaningful rejuvenation: aging is damage, and slowing down the damage does nothing for people who are already old and damaged. Yet there are other research strategies that can achieve this goal: the better approach is to repair the damage that causes aging, following the existing detailed research plans that aim to produce new rejuvenation biotechnologies. These can in principle restore youthful function for the old, extend healthy life indefinitely, and should not be any more expensive to explore and develop than a continued future of whatever the next replacement for sirtuin research might be. If billions are spent, then let it be in the pursuit of technologies that do offer the possibility for everyone to live to 90, and in good health, lacking frailty, pain, and disease.

It's a fight to make this case. It shouldn't be, but it is. Attention continues to be soaked up by marginal, ultimately pointless efforts such as the one noted in the article below. It won't let you live to be 90 in confidence, it won't create rejuvenation in the old, and no foreseeable evolution of this strategy can in fact provide those benefits. It is just more of the same search for the greater fool to retroactively bankroll the continuing mapping of metabolism.

The Anti-Aging Pill

An anti-aging startup hopes to elude the U.S. Food and Drug Administration and death at the same time. The company, Elysium Health, says it will be turning chemicals that lengthen the lives of mice and worms in the laboratory into over-the-counter vitamin pills that people can take to combat aging. The startup is being founded by Leonard Guarente, an MIT biologist who is 62 ("unfortunately," he says) and who's convinced that the process of aging can be slowed by tweaking the body's metabolism.

The problem, Guarente says, is that it's nearly impossible to prove, in any reasonable time frame, that drugs that extend the lifespan of animals can do the same in people; such an experiment could take decades. That's why Guarente says he decided to take the unconventional route of packaging cutting-edge lab research as so-called nutraceuticals, which don't require clinical trials or approval by the FDA.

This means there's no guarantee that Elysium's first product will actually keep you young. The product contains a chemical precursor to nicotinamide adenine dinucleotide, or NAD, a compound that cells use to carry out metabolic reactions like releasing energy from glucose. The compound is believed to cause some effects similar to a diet that is severely short on calories - a proven way to make a mouse live longer.

Elysium's approach to the anti-aging market represents a change of strategy for Guarente. He was previously involved with Sirtris Pharmaceuticals, a high-profile biotechnology startup that studied resveratrol, an anti-aging compound found in red wine that it hoped would help patients with diabetes. That company was bought by drug giant GlaxoSmithKline, but early trials failed to pan out. This time, Guarente says, the idea is to market anti-aging molecules as a dietary supplement and follow up with clients over time with surveys and post-marketing studies.

Comments

Reading this made me realize why google started up and funded CALICO, and ignores to help SENS. Calico studies calorie restriction, along with other anonymous things i was not able to learn of. While SENS is a none profit organization which research involves repairing the damage rather then creating a magic pill. Pills may be involved of course for certain things, but it's not the goal to create one.

No matter what, I don't think you can really convince someone to donate to SENS because you can't really profit monetary wise by doing so. Even if what SENS is doing is right. The only way to make SENS gain a larger sum of donations is by gaining government funding I imagine.

Posted by: thatoneperson at February 4th, 2015 5:00 AM

Essentially, this was lets seee... about like 8 months ago? But when I talked to scientist in Calico ways they viewed aubrey where "his opinions where outlandish, and quite extreme. Such bold claims that may not be 100% true can hurt the research field if proven false and turn away heads who may otherwise be interested in the field"

So i suppose it was a combination of things to why they do not help SENS. If they funded SENS, and they did not provide amazing results, it would de-legitimize google.

Posted by: thatoneperson at February 4th, 2015 5:20 AM

"Such bold claims that may not be 100% true can hurt the research field if proven false" - Are you sure this guy was an actual scientist? If anything substantial in this whole business can be categorically proven false it would represent a huge leap in understanding. Proving things false is how knowledge advances. Do you still know the guy? Is there any way you could get him in here and maybe ask him what Calico is actually spending all that money on?

Posted by: Slicer at February 4th, 2015 10:39 AM

I think me trying to type what i remember doesn't do it justice so I just copy pasted some of it, i'll keep the names anonymous though

"I don't think Calico needs to give him any credit. He didn't come up with the idea of working on aging as a research topic and as an angle to find new therapeutics. This idea is at least 25-30 years old. Many scientists started this approach long time before he communicated widely and wildly to the public his theories. Leonard Hayflick, Harman, Brian Kennedy, Cynthia K, Leo Guarente, etc. it's just that they were more busy in the lab than communicating to the public and journalists.

I think his contribution to the popularization of our research can be good and bad at the same time. Good that someone put so much energy in advertizing this approach, to tackle aging to find new treatments for cancer for example., it can bring $$ to the field. However his tendency to go way beyond what the science allow us to speculate could scare others and induce strong negative opposition to it, in an epidermic/superficial way.

I work on rejuvenation. I found worms rejuvenate all the time, naturely. I described that they can age before they reach adulthood, when they are starved. I m now trying to figure out how, what's the genes involved. This work is already public since I've presented it at several meeting but not published yet."

I feel thats all i'll paste though in the conversation, I mean one of their calico founders works on worms so her branch does the exact same thing, which is what reason detest. The whole calorie restriction research. I never bothered delve much deeper in what the other scientist do

Posted by: thatoneperson at February 4th, 2015 1:21 PM

I don't really know enough to build much of a opinion, I mostly just waddle about and ask questions. I don't know the reasoning to why they would avoid SENS, what the other scientist do, if the work overlaps, if their work already made more progress, or whatever. It makes it tough for me to decide on what to do about it all

Posted by: thatoneperson at February 4th, 2015 1:25 PM

"He didn't come up with the idea of working on aging as a research topic and as an angle to find new therapeutics."

AFAIK, Aubrey de Grey never claimed that. What he claims is that his approach to defeat aging (namely, SENS) is new, not that he is the first person that tried to defeat aging.

"Many scientists started this approach long time before he communicated widely and wildly to the public his theories. Leonard Hayflick, Harman, Brian Kennedy, Cynthia K, Leo Guarente, etc. it's just that they were more busy in the lab than communicating to the public and journalists."

I don't know about the others, but Hayflick thinks that curing aging is a bad idea:

https://www.fightaging.org/archives/2004/07/commenting-on-leonard-hayflick.php

"However his tendency to go way beyond what the science allow us to speculate could scare others and induce strong negative opposition to it, in an epidermic/superficial way."

AFAIK, nobody has proven that SENS is beyond the reach of science. OTOH, there are good evolutionary biology reasons to think that studying rejuvenation genes in other species will only produce modest life extension in humans, if at all.

Posted by: Antonio at February 4th, 2015 1:59 PM

This is very disappointing. The guys at elysium health were involved with sirtris, so they will have seen first hand evidence from their experiments that these substances do not increase lifespan or healthspan. But instead of going back to the drawing board and trying something else, they've instead decided to try and cash in on their hard won reputations by selling snake oil to desperate people.

Posted by: Jim at February 5th, 2015 4:25 AM

If GlaxoSmithKline has invested the $720 million paid for Sirtris into SENS it would have achieve a lot more. Frankly when GlaxoSmithKline announced in 2013 it was closing down Sirtris Pharmaceuticals it just showed what a terrible waste it had been. I wonder what Aubrey de Grey and SENS could do with $720 million? My guess is quite a lot.

Posted by: John Andersen at February 12th, 2015 9:42 AM

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