Leonard Guarente's Anti-Aging Pill

You probably recall the hype surrounding sirtuins in cellular metabolism, followed by the breathless marketing of compounds supposed to affect their expression such as resveratrol, all of which went to the usual destination for such things, which is to say nowhere. Some knowledge was added to the grand map of mammalian biochemistry, some people were fleeced, some people made a bunch of money on the backs of promises that never materialized, and that was that. This happens over and again. Every time a new link is uncovered in the complex chain of protein machinery relating to cellular repair mechanisms, upregulated in many of the ways to extend life in lower animals, or calorie restriction, a practice that extends life in short-lived mammals such as mice, and along the way alters near every aspect of the operation of metabolism, then the marketing begins for any supplement that can be linked, tenuously or otherwise, to that research.

If you recognize the general pattern, then you should be well placed to see how things will play out for nicotinamide riboside. This is yet another molecule that can be used as a supplement, and which influences some of the mitochondrial biochemistry associated with cellular maintenance processes. In mice it has been shown to modestly reduce some forms of age-related decline, either by spurring greater maintenance or greater stem cell activity. It is an open question as how much of this will be recapitulated in humans; short-lived species are much more readily influenced by this sort of thing. Their life spans are plastic, and so are their metabolic operations. Regardless, it is of course the case that a bunch of people got together to form a company in order to sell nicotinamide riboside as a supplement. That company is called Elysium Health.

The differences between this and past efforts of this nature are that (a) more reputable scientists from the aging research field are involved, more is the pity for their reputations, and (b) the whole affair is just a little closer to a sensible take on how to make progress in the field, rather than being an absolute money grab. In fact I agree with a fair bit of what cofounder Leonard Guarente has said in public on his motivations for doing this: that progress must be made more rapidly, that there is a space between the worthless supplement market and the highly regulated world of medicine in which good work can be done, and that it is important to put new approaches out there in the world to gather data. I just don't think that this particular approach has any merit in and of itself. My position on tinkering with metabolism via drugs and found compounds in order to gain tiny and dubious benefits is that it is a a waste of time and effort, and definitely not the road to meaningful outcomes in the treatment of aging. Further, even putting that to one side, the founders of Elysium haven't gone about this in the right way at all. They should have sold their product as an open trial of nicotinamide riboside wherein people pay for participation, doubled the price of the supplement, and used that extra money to collect data from participants. Instead they, as everyone is, are corrupted by the fiduciary duty that comes with running a company where the primary focus is selling a branded supplement - so now they are in the supplement business, not the science business. It should be an object lesson for the next group who are thinking of doing something like this.

I'm very much in favor of freedom. For my money, all of medicine should be as open as this: that anyone can invest the time and money to package and sell a product, that consumers can easily find all of the research online to read up on what the scientific community has to say, and that reviewers can take that information to provide digests for those who don't want to read the research. Freedom means the existence of marginal products as well as great products, and people doing things you personally think are a waste of time as well as people doing things you agree with, but you can always identify these as such. You just have to take a little time to read around the topic before you reach for your wallet. Freedom also means a far greater set of activity and greater experimentation and availability of new approaches than would take place if all of this was hammered flat beneath the cost of regulation, and that, I think, would be worth the price of admission. Successes will prove themselves by virtue of the fact that sellers will find it worth the cost of setting up formal trials to demonstrate effectiveness, for example.

"But he has also seen public funding of aging research, never particularly robust, become even scarcer."

It seems like this part, at the end of the article, might explain while Guarante is risking his reputation with Elysium. In the absence of public funding, his only options are to depend on the largess of billionaires like Thiel, or form a business and try to retain enough control to set the research agenda.

I suspect Elysium will end-up with a breach between him and his business partners, much like his previous company. There's a basic incompatibility: Actual anti-aging research is expensive, and won't deliver practical results for decades (if ever), while actual profits in anti-aging come from selling regulation-skirting supplements that almost certainly don't work.

Since there's no actual reliance from the profit-making part of the business on the research department, the suits will see it is a large and unnecessary cost, sooner or later. The presence of Guarente and his peers provide a necessary veneer of respectability right now, as they're establishing themselves in the market, and guarantee publicity like this article that it would never otherwise receive. But once they're established, I'm guessing they'll decide they can do without the scientists and the research, and Guarente will be looking for another source of funding once again.

Reasons to be cautious:

>Moreover, even if NR supplements do provide an immediate jolt to muscle mitochondrial metabolism in the way that the Harvard NMN studies suggest, it’s not clear that doing so is a good idea in the long term. NMN injections don’t improve mitochondrial function by repairing molecular damage wrought by the aging process in the organelles, nor in other cells and biomolecules whose damage with age results in a dampening-down of mitochondrial activity. Instead, NMN injections leave the existing damage in place, and induce the still-functional mitochondria to work harder and pump out more energy. This is rather like pushing harder on the gas pedal when your car is not running at full power due to damage to its cams and push rods: it may make the car go faster in the short term, but the underlying damage hasn’t been fixed, and will likely get even worse from the excessive wear.

http://www.sens.org/research/research-blog/question-month-12...

"Guarente has a third child ... but is unable even to find him, because he is a computer programmer specializing in encryption who has managed to scrub the internet of clues to his whereabouts" This made me chuckle

"After a rocky start — in his memoir, Ageless Quest, Guarente cops to quitting smoking when he was in third grade — he has lived a generally healthy life. Besides Basis, he takes a low-dose statin, aspirin, and vitamin D; weighs himself every day; eats a mostly Mediterranean diet (red wine included); and does a mix of cardio (on the elliptical machine, ever since his knees wore out and he had to stop running) and strength training three days a week at a gym near his home in the Boston suburb of Newton."

This is a pretty sensible anti-aging regimen. Vitamin D and baby aspirin reduce all-cause mortality in the elderly in the meta-analyses, statins are probably helpful, daily weighing will help avoid obesity and metabolic disorder leading to all sorts of bad things like diabetes, and likewise the cardio & weight training. Such a regimen is probably good for at least 2 additional years of life expectancy. If he was going to add anything more, it would have to be metformin or low-dose rapamycin, and those are speculative enough that one might want to wait for TAME/MILES results before deciding.

A few of the molecules mentioned in the article:

Pterostilbene 50mg: https://en.wikipedia.org/wiki/Pterostilbene

Nicotinamide riboside (NR) 250mg: https://en.wikipedia.org/wiki/Nicotinamide_riboside

NR is a precursor to nicotinamide adenine dinucleotide (NAD+): https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleot...

In a first-world, disposable income scheme of things, I guess $60 a month isn't bad. Your cellphone bill is probably higher.

But what Bill Gates said last year in a Reddit AMA resonates with me: "It seems pretty egocentric while we still have malaria and TB for rich people to fund things so they can live longer."[1]

I'm reminded of an inscription that appears on English gravestones going back to at least the 1500s:

  If life were a thing that money could buy,
  The rich they would live and the poor they would die;
  But God in His goodness hath ordered it so
  That the rich and the poor they together must go.

Maybe not for much longer.

[1] http://www.washingtonpost.com/sf/national/2015/04/04/tech-ti...

been taking this supplement for several months. Improvement in sleep quality and wakefulness was pretty noticeable on the second day. Had no idea how 'brain-fogged' I felt prior to taking it. It seemed to help recovery time with respect to exercise and I overcame some plateaus while taking it. Another fringe benefit I've noticed is that hangovers from drinking are non-existent. Would definitely recommend trying it, but your mileage may vary.

Chromadex also sells the same supplement but I do not know of any differences between what they provide and what Elysium provides.

Tried it for two months. No noticeable effect. Didn't continue.

Basis elevated my blood sugar quite dramatically. Beware, and check your blood sugar when you're on it (against your normal baseline) It did that on day one and day two so I quit taking it and now back to normal levels for blood sugar.

I'm reminded of something heard long time back:

  Everybody wants to go to heaven but nobody wants to die.

After reading up on a bunch of papers on NR, I decided to try it for a month. I found that I have noticably better sleep in terms of deep sleep vs light sleep (as quantified by a sleep tracker) and faster muscle recovery after bike rides. I just signed up up for a 1 year subscription. YMMV

This sounds a lot like Theranos.

> “But frankly, I’m kind of shocked all those big-name scientists signed on to this thing that’s two very common, easily obtained supplement ingredients.”

I don't know why this is so shocking. It sounds pretty rational.

Bruce Ames is a similarly eminent scientist interested in anti-aging research. He's tried to commercialize his research into Acetyl L-Carnitine and R-Lipoic Acid.

I am not sure if this is scientifically proven or not but I have seem people who stay off sugars, starches, and alcohol look atleast 10 years younger.

Eh, nature has already optimized for maximum human lifespan, and it seems to be a tad past 100. It's a nice round number. Personally I don't mind it, give or take a few decades.

It'll be great when we finally break through it. Think of all those extra years we can spend looking at websites on our cell phones.

We changed the title of this rather substantive profile piece to make it less baity, but if anyone can suggest a better (more accurate and neutral) one, we can change it again.