
Leonard Guarente’s Anti-Aging Pill (2016) - honorable
http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-fountain-of-youth.html
======
amelius
This paragraph summarizes the theory behind the pill.

> The theory behind Basis is in part an evolution of the theory behind
> drinking red wine: One of its main ingredients, pterostilbene, is considered
> a more powerful version of resveratrol, with a more convincing track record
> in the lab. As for NR, by increasing NAD levels in our cells, it in turn
> appears to reverse mitochondrial decay. In a 2013 scientific paper, Sinclair
> announced that a single week of injections of an NAD precursor into elderly
> mice had made their muscles look young again, though without restoring their
> strength. Both compounds aim to activate sirtuins, and the hope is that
> together they might amplify what each does individually.

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sanxiyn
Fight Aging! is a long running blog on longevity science (now more than 10
years old) and their take is usually worth reading. Here is their take on
Elysium Health: [https://www.fightaging.org/archives/2016/07/an-
educational-a...](https://www.fightaging.org/archives/2016/07/an-educational-
article-on-the-business-of-selling-nicotinamide-riboside/)

------
monochromatic
[http://blogs.sciencemag.org/pipeline/archives/2016/04/25/sub...](http://blogs.sciencemag.org/pipeline/archives/2016/04/25/subtle-
changes-can-be-yours-for-fifty-dollars-a-month)

I'll pass.

~~~
amelius
> anyone who starts talking about “detoxification” and “toxins” is likely to
> be a quack. It’s a buzzword, something that plays to peoples’ mistaken ideas
> about medicine and biochemistry, that there are all these toxins from the
> environment that have to be flushed out somehow for you to be healthy.

Is this true? Waste products need to be transported out of the cells and their
environment, right? And they can be toxic. Why is this a controversy?

~~~
beagle3
The word "toxins" induces guilt by association because most who use it are
quacks. However, there definitely are substances that are toxic and get stored
e.g. in adipose tissue and only removed under specific circumstances. But we
have to find new names for those substances and processes because of that
guilt by association.

~~~
amelius
But there's a whole scientific field called "toxicology".

Anyway, I don't like the phrase "anyone who ... is likely to be ..." in the
linked article. It's basically an ad hominem attack, and not very scientific
in itself (unless you take it literally, but in that case the author should
have been more explicit imho, to avoid confusion/insinuation).

~~~
Doxin
Correct, and a toxicologist would be able to tell you which toxin specifically
is being targeted by a treatment. A quack not so much.

------
fraqed
Previous discussion on this article:
[https://news.ycombinator.com/item?id=12345526](https://news.ycombinator.com/item?id=12345526)

------
reasonattlm
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 here 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 here. 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.

\-----

You might 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. Regular readers will know my position on tinkering
with metabolism via drugs and found compounds in order to gain tiny and
dubious benefits. 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.

~~~
p1esk
tldr?

~~~
JPLeRouzic
Probably Reason says that there will never a pill against aging, because aging
is a complex process and it cannot be solved by a quick and dirty trick.

(I am just trying to summarizing, not giving my own opinion)

~~~
sanxiyn
I think the better summary would be "there will never be a pill against aging
that works through altering metabolism, ultimately mimicking calorie
restriction". The reason is simple: even calorie restriction is not a solution
to aging, so calorie restriction mimic can't be. I think this is obviously
correct.

I think Reason is neutral about other ways against aging which is not through
metabolism.

~~~
p1esk
There's nothing "obvious" about aging, and we don't even understand how or why
calorie restriction works [1].

[1]
[https://en.wikipedia.org/wiki/Calorie_restriction#Mechanisms](https://en.wikipedia.org/wiki/Calorie_restriction#Mechanisms)

