
Leonard Guarente's Anti-Aging Pill - wallflower
http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-fountain-of-youth.html
======
reasonattlm
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.

------
stupidcar
"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.

------
KVFinn
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...](http://www.sens.org/research/research-blog/question-
month-12-energy-carrying-molecules-boost-aging-mitochondria)

~~~
spaceheeder
Isn't SENS the exact organization that Elysium's existence is premised on,
err, not existing? They're actively doing research into the causes of aging,
themselves being precursors to causes of age-related diseases. It's just that
slow, rigorous, peer-reviewed research that leads to specific therapies with
known human health effects take time and money to produce. Can anyone explain
why so many scientists would rather attach their names to Elysium than to
SENS? I want to hold them in higher regard than to assume it's just money.

------
ceilingscorpion
"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

------
aab0
"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.

~~~
BatFastard
Indeed it is sensible.

Honestly at this point in my life (58), I have more of a desire to feel great
everyday then I do to have 2 more years of life when I am 93.

~~~
agumonkey
Same here. I wish I knew more about how to maintain and even improve my overal
well being. Maximizing my potential on this bounded time.

I find society very lacking there. Feels even diminishing returns since our
culture, driven by recent economy; optimizes for consumption of safe and
regular but low grade and low diversity products. Also stressful lifestyles ..

------
applecore
A few of the molecules mentioned in the article:

Pterostilbene 50mg:
[https://en.wikipedia.org/wiki/Pterostilbene](https://en.wikipedia.org/wiki/Pterostilbene)

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

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

------
helloworld
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...](http://www.washingtonpost.com/sf/national/2015/04/04/tech-titans-
latest-project-defy-death/)

~~~
tomcam
About this quote by Bill Gates, whom I admire greatly:

 _" It seems pretty egocentric while we still have malaria and TB for rich
people to fund things so they can live longer."_

Bullshit. It sounds great, but what's it's really saying is that Bill Gates is
a better judge of what should be done with Leonard Guarente's time than
Leonard Guarente. That kind of talk is insidious. First of all--what are we
going to do, all submit to Bill Gate's idea of what we should do? If not Bill,
then, who will decide?

It ignores the fact that the research of people like Guarente could end up
right in Bill's wheelhouse. Many great scientific discoveries were accidents.

It also completely ignores the fact the Bill himself became a great force for
good not by doing what some factotum told him what to do, but by doing
something that everyone told him not to do. Who knows, maybe Guarente will
make a trillion dollars on his research (which I have absolutely no interest
in). If Bill had done what his parents wanted him to do he probably would have
been a white-shoe lawyer in Seattle or CEO of Planned Parenthood.

I think Bill is a severely underrated CEO and probably a well-intentioned
human being, but Bill has no fucking business telling the rest of us what to
do with our time.

~~~
porkloin
It's called an opinion, and yes, even billionaires-turned-philanthrophists are
entitled to them. :)

Don't worry, though - it'll be at least another 10 years or so until Gates
starts sending his cronies out at night to black-bag folks into compulsory
humanitarian aid work.

~~~
intrasight
I was under the impression that they had already started doing that ;)

------
WeEatnKid
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.

~~~
daveguy
> 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.

Two questions:

1) What do you think about the idea of not taking it anymore?

2) Did you quantify your plateau breakthroughs and can you compare them to any
previous plateaus?

~~~
WeEatnKid
1) I am reluctant to stop taking it. I am accustomed to the initial effects --
a missed dose here or there isn't noticeable, but I don't want to lapse into
fatigue from abstaining or miss out on the benefits of sustained intake. There
may not even be a benefit to long term supplementation so this concern is a
bit unsubstantiated.

2) I didn't track or log differences in my exercise routines so I can't
quantify anything. Qualitatively, its easier to exercise consecutively and I
have been able to increase magnitude on my lifts by ~20% across the board.
This could be attributed to shorter recovery time and reaping the benefits of
adding volume to training. The strength gains plateaued 6 months in. I am in
my 8th month of taking basis.

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

~~~
DennisP
I'm guessing you don't feel noticeably older right now than you felt two
months ago. So if the pill merely slows aging, rather than reversing it, it's
not likely you'd notice any change.

~~~
godshatter
Even reversing aging would presumably take a not-insignificant portion of a
person's life span. If the rate were magically the same as aging, just in
reverse, it could take years to notice the difference depending upon your age.

~~~
reasonattlm
Reversing aging doesn't work that way. Aging is damage, and reversal of aging
is damage repair. Damage repair can be rapid and sweeping, and usually is.

You might examine some of the animal studies for, say, stem cell therapy or
senescent cell clearance. Benefits are rapid and very evident for things that
do actually work. Even slower items like myostatin blockade to provoke muscle
growth show sizable, obvious benefits over a period of a few weeks to a few
months.

~~~
godshatter
I agree, that's why I used the word "magically".

------
ilostmykeys
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.

------
0xmohit
I'm reminded of something heard long time back:

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

------
tahoeskibum
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

------
pboutros
This sounds a lot like Theranos.

~~~
blackbagboys
Could you elaborate? Unlike Theranos, this company's founders are remarkably
accomplished and upfront about the speculative nature of their product.

~~~
pboutros
Sure! And that's true. I'll also add that the board packs a _far_ stronger
scientific punch than Theranos's originally did.

It reminds me of Theranos because it meets the 'visionary founder(s) +
unproven yet promising sounding scientific premise + extensive backing from
prominent individuals = really great story to read/write about'. The caveat
there is, as I mentioned, the significant scientific backing behind this.

I am very skeptical of dietary supplements (esp. when they aren't something
like niacin, or iron, which have permitted claims). I am not a lawyer, but it
would seem to me like their marketing might run close to afoul of FDA guidance
on dietary supplement claims. See here
([http://www.fda.gov/food/guidanceregulation/guidancedocuments...](http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/dietarysupplements/ucm073200.htm)).

Here are a couple examples of them artfully avoiding making seriously
problematic claims:

\--- "Basis is designed to optimize NAD+ levels and sirtuin function in our
cells to support our most critical metabolic processes like cellular
detoxification, DNA repair and energy production."
[https://www.elysiumhealth.com/basis](https://www.elysiumhealth.com/basis).
Note the careful language use of 'support', which doesn't actually mean that
it does it, according to the FDA guidance document cited above.

"It is closely related to resveratrol, a compound found in grapes and red
wine, but more bioavailable, or easier, for the body to incorporate. Research
has shown that pterostilbene, like NAD+, stimulates enzymes called sirtuins.
They relate to critical cellular processes, from aging to circadian clocks to
energy production."
[https://www.elysiumhealth.com/basis](https://www.elysiumhealth.com/basis)
Note that they mention the critical cellular processes as related to it,
without directly saying that consuming more of pterostilbene actually helps.
\---

The claims themselves aren't direct enough to probably merit a warning letter
(in my amateur opinion), but it certainly doesn't mean that they do anything.
They aren't actually making any claims as to the product's efficacy, but if
they were to, you'll also note that all of the research
cited([https://www.elysiumhealth.com/basis](https://www.elysiumhealth.com/basis),
at the bottom) probably wouldn't actually substantiate any claims per FDA
guidance, because the studies don't actually come close enough to testing the
supplement itself.

I say all of this under the caveat that I am not a lawyer, just a regular
human being who is skeptical of any miracle pills.

~~~
darawk
They are doing that because making those claims would be illegal. So, the
absence of the hard version of these claims doesn't really mean anything,
because if they did make them they wouldn't be able to sell their product at
all.

~~~
pboutros
So, what's the point of the product, if it doesn't do anything? Or, if it does
something, why don't they find the proof, and substantiate it?

~~~
dsr_
The FDA has three classifications: food, which must be good for you; drugs,
which must be effective; and supplements, which must not poison you.

It is much more profitable in the short-term to make a supplement and sell it
to millions without prescriptions than to make a drug and sell to thousands
with Rx.

If they spend money on trials and subtantiate their hypotheses, they have to
stop selling it as a supplement because now they know it is a drug... but as
long as they don't run the trials and don't know it's a drug, they can keep
going.

~~~
pboutros
>If they spend money on trials and subtantiate their hypotheses, they have to
stop selling it as a supplement because now they know it is a drug... but as
long as they don't run the trials and don't know it's a drug, they can keep
going.

Stands in contradiction with this (in the article).

>The company stresses that it is using only compounds supported by hundreds of
peer-reviewed papers, that it enforces high manufacturing standards, and that
it is conducting a human trial (currently 120 people between the ages of 60
and 80 are participating)

\--

Your overall point about how it's a profit seeking venture first and foremost
is accurate. Personally, I find it ethically wrong to imply that your product
will help people without knowing for sure that it will. There's always the
edge case where the less savvy consumer goes for the ineffective supplement
instead of consulting with their doctor.

------
0xdeadbeefbabe
> “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.

------
nwah1
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.

~~~
RhodesianHunter
I would imagine commercializing ALCAR to be be difficult at this point,
considering you can get it cheaply in every form on Amazon Prime.

~~~
nwah1
I think that is why there was a lot of hype about R-Lipoic Acid for awhile, as
opposed to regular lipoic acid. And a lot of hype about Acetyl Carnitine
Arginate.

You can patent the manufacturing processes on this stuff, even if you cannot
patent the substance itself.

Nicotinamide Riboside and pterostilbene's manufacturing processes are patented
by a company called Chromadex.

------
perseusprime11
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.

------
matt_wulfeck
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.

~~~
thangalin
> nature has already optimized for maximum human lifespan

Doubtful. The bowhead whale, which lives over 200 years[1], has mutations that
we lack. Given that mutations happen randomly and that the dolphin genome is
basically the same as the ours (with a few chromosomal rearrangements)[2], it
suggests that bowheads got lucky in ways humans did not. A mere fluke.

Evolution hasn't finished with us, either.

[1]:
[https://en.wikipedia.org/wiki/Bowhead_whale#Lifespan](https://en.wikipedia.org/wiki/Bowhead_whale#Lifespan)

[2]:
[https://www.karger.com/Article/Pdf/15002](https://www.karger.com/Article/Pdf/15002)

------
dang
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.

~~~
Retric
How about, _A Fountain of Youth Scam_

~~~
dang
Since that's not even close to neutral, it doesn't seem like you posted it in
good faith. Please don't do that. I'm skeptical of the subject matter too, but
flipping from hype to denunciation is not what we're looking for here. In fact
those two things are variants of one another.

~~~
__jal
"Human longevity embiggenator candidate #318621"

And I can promise you I'm posting this in good, er, spirits.

