
Age Reduction Breakthrough? - James_Henry
https://joshmitteldorf.scienceblog.com/2020/05/11/age-reduction-breakthrough/
======
maxander
Since it seems like the upshot of all of this is that Katcher is claiming to
have discovered a set of signalling molecules which, when injected, rejuvenate
tissue and presumably lengthen life, it runs into one of the most fundamental
objections that can be leveled at theory of aging (or cure thereof): of the
billions of humans that have existed, how is it that _none_ of them have
possessed a mutation which (in this case) endogenously produced the signalling
molecules which Katcher is proposing as treatment? In the case of this
proposal this sort of objection is particularly strong, since (though the blog
post is silent as to what the treatment is) it's given that they are fractions
from blood, so they're substances which the body produces in some quantity
anyway, and which are sufficiently non-dose-specific that Katcher, with
limited resources, could devise a reasonably effective regimen.

Parabiosis is one of the most striking (and just weird) phenomena in aging
research, so efforts to understand what's going on with it are liable to bear
interesting fruit. I'm just pointing out that there's good reason to doubt
that this particular "breakthrough" is the "cure."

~~~
eganist
At risk of sounding absolutely insane:

There's probably no way to prove that this hasn't happened. Anyone who
realizes they're not aging normally would likely have taken on a new identity
elsewhere for fear of:

1\. being burned at the stake

2\. being trialed in repeated experiments

3\. being deified, and then subsequently being burned at the stake.

\---

I realize my comment sounds like a joke, but I'm entirely serious. If you or I
found out we're not aging normally and look e.g. 25 by the time we reach 40,
or 30 by the time we reach 45, would either of us remain in our current lives?

~~~
steelframe
Someone I work with looks very youthful for their actual age, and that isn't
always a good thing.

When the team went on an offsite morale event jet skiing, he was told by the
proprietor that he couldn't participate because their policy requires you to
be at least 16 years old. He was 27 at the time. He never lived that down with
his peers. When he tries to go to a bar with friends, he's sometimes accused
of trying to pass off a fake ID. These experiences are deeply embarrassing for
him.

Imagine trying to get promoted to a senior director position at a company
while looking like you are fresh out of college. In that case ageism takes a
different meaning.

~~~
gotrythis
I think people age at different rates.

My Dad is in his mid 80's and plays four hours of sports a day, or at least he
was before the pandemic hit.

When I was in my mid-20's I had to impress the hell out of potential clients
to get work, as I looked like I was 15, and girls my own age wouldn't look at
me as I was too young. I never drank, so bars weren't an issue. When I was in
my early forties, 15-20 year old girls were still coming on to me. I will be
50 next year, and I finally look like I'm in my 20s or 30s, and still get
those looks from University-aged girls whenever I venture where they hang out.

A couple of years ago, my now 43 year old partner was mistaken for her teenage
doppelganger and asked to the high school prom by three different boys while
walking home from work.

It was annoying earlier, but now I look forward to turning out to be one of
the immortals.

~~~
xwdv
One thing to remember is that people don’t have perfect vision either. As long
as you are not out of shape or have sagging skin or gray hairs, people will
not be able to clearly see any wrinkles or other textures in skin that would
give away age.

In general I’ve seen a lot of people that look young for their age but when
looking at their skin up close on their face, neck or hands it gives it away.
Women are also at an obvious advantage through their use of makeup.

------
peter_l_downs
As someone entirely outside this field, can someone with more inside knowledge
give any insight into where this lies on the crank/hoax spectrum? A biorxv
paper and a well-written blogpost don't really point either way.

~~~
amluto
When the author says things like:

> But Katcher has no research grants or university lab or venture capital
> funding, no team of grad students mining databases and screening chemicals
> in the back room.

> One thing Katcher has going for him is the correct theory.

I start to suspect the author’s opinion is stronger than their evidence.

~~~
coryfklein
Given that many major scientific discoveries occurred with the prototypical
mad scientist working alone, often apart from their main field, this
description doesn't seem out of the norm for what I'd expect in somebody
trying to urgently raise the signal of a very early and promising discovery.

Let's consider the universe where Katcher _has_ discovered the secret to
aging. At some point in that universe, Katcher's work is going to be
relatively unknown and unsponsored, and at a later point there will be
trillions poured into it. The above quote you posted aligns just fine with the
earlier part of that timeline so now you're just left to decide, given your
priors about major scientific discoveries, how likely it is that a major
scientific discovery can come from a "dark horse".

~~~
koheripbal
That may have been true a century or two ago, but that seldom occurs anymore
now that scientific discovery has matured into an industry.

The vast vast majority of research discoveries happen within the system as
part of large collaborations.

It's always healthy to have people going against the grain, but even they can
find funding if they have ideas they can express coherently and that stand up
to scrutiny.

~~~
wegs
This is still true. Your second sentence is correct, but the rest is not. Most
research does come from within the system. Unconventional research does not
and cannot come from within the system.

Funding comes from calls from proposals which are within existing, established
research fields. Funding outside of a current research field is nearly
impossible to find. If your research isn't in an established field, there
isn't an NSF/DARPA/etc. call to respond to, and there is no program officer
who has any interest in your work.

Similar through the whole research pipeline. New areas of research don't have
established venues where you can publish, people to cite your papers, or a
community to write academic reference letters for you. People who work in new
fields are usually doing so as nights and weekends projects, or are
independently wealthy.

And although the vast majority of independent researchers are crackpots, a few
are credible and do occasionally make major breakthroughs. Importantly, the
majority of breakthroughs outside of established fields are made be people
unsupported by NSF, and without good venues to publish (although quite often,
those individuals are academics working in their spare time, so half within
the system and half outside).

------
babesh
Was told by my wife years ago that there is a Hong Kong tycoon who has been
doing this for years. Supposedly hires young people to do nothing but to stay
healthy and then has transfusions of their blood. Just checked and he is still
alive at 91. But this echoes vampire.

This reminds me of plasma treatment for covid-19 which is actually proven.
Perhaps someone will create a market for that.

~~~
Ididntdothis
90 is not that old these days. Both of my parents have reached their 90s
without doing anything like this. Let’s take a look at that guy in 20 years
and see how he is doing.

~~~
coryfklein
> 90 is not that old these days

True but Hong Kong life expectancy for men is 81.3 years so one should still
consider this evidence in favor of the man doing something that extends his
lifespan. Doesn't need to be smoking-gun level but still: update your priors.

~~~
4gotunameagain
n=1

~~~
babesh
I'm not going to take a side here but just wanted to point out that the
previous poster is referring to conditional probability.

P(works|someone doing this is 91) > P(works). n is 1 here so the probability
hasn't changed much at all.

------
busyant
I thought one of the main purposes of research publications was to allow
others to reproduce/verify or refute your work.

If you look at the methods section, here is what you get for a description of
the magic plasma:

'We used a unique plasma fraction "Elixir" developed by Nugenics Research.'

This seems to run counter to the philosophy of reproducibility.

[https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1....](https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full.pdf)

~~~
lwansbrough
To be fair, this would be a contender for the most epic discovery in human
history. Would you simply give the solution away?

~~~
busyant
If that's my primary concern, I wouldn't publish until I had the patents
nailed down.

------
rantwasp
Improving longevity is what the people at
[https://www.lifespan.io/](https://www.lifespan.io/) have been trying to do
for ages. The research is being done, there are tons of new promising things -
with the catch that they are experimental / not tested on humans.

Before you get too excited and wonder where you can buy these magic pills,
remember that there are things you can do right now to improve both your
longevity and your quality of life: 1) sleep properly 2) eat properly 3)
exercise 4) reduce stress

That being said I think that the next 20-30 years are going to be really
interesting in this space, and if we indeed have any sort of proven
breakthrough this will force us to rethink how we think about our society and
our mortality.

~~~
koheripbal
I believe the most impactful thing you can do is drastically reduce caloric
intake - like by 50%.

Experiments have show large increases in lifespan, across mammals.

~~~
zemvpferreira
It's weird to me to say so but this intervention is one of the few things
that, even if it were to demonstrably increase my lifespan from ~80 to ~120
years, I probably wouldn't do.

I don't know if that's because I enjoy food and bodily activity too much to
value a longer life without them or because I'm addicted to food. I've
wondered.

What wouldn't you be willing to give up for a much longer life?

~~~
saiya-jin
Depends which parts gets prolonged - if you are at 80 deteriorated +-same as
somebody who dies at 80, and they just keep fixing the next thing that is
going to kill ya, then yes, that's a pure physical misery and spiral down
progressive dementia (almost all old folks suffer from some form of it).

Now if we would be 40-like in our 60s and so on, that's another story. But
first thing that would probably change is retirement age.

~~~
zemvpferreira
Is being 40 and not being able to play tennis or go on long walks because
you're too calorie-deprived that different from being 80?

~~~
koheripbal
That isn't the outcome though. Those on these strict diets are not lethargic.

~~~
zemvpferreira
From my own experience doing extreme diets I highly disagree. As soon as your
own bodyfat starts getting low, being on a ~1500 calorie diet as an adult male
is extremely exhausting by itself. No chance of enjoying physical activity
whatsoever.

------
floatrock
> Most of the explosion in aging research (and virtually all the venture
> capital startups) are looking to treat aging at the cellular level.... The
> truth, as Katcher understands it, is that, to a large extent, aging is
> coordinated system-wide via signal molecules in the blood.

So the SV execs with their fit young blood-bois were right all along?

~~~
andreygrehov
I had the exact same thought. I wonder where those execs get the information
from and more importantly, how the information is filtered, because they are
clearly a few years ahead of what's being posted on, say, HN.

~~~
maxwell
It was widely reported years ago. The future is already here it's just not
affordable.

I remember talking about recent news that a few of us had heard about
promising "young blood rejuvenation" with a bunch of random hicks in the woods
of central Maine in the spring of 2014.

------
greyhair
You may be able to slow aging, but you are still going to deal with wear and
tear. Until they actually find a way to promote well regulated regrowth of
tissue, that is going to be a problem. I am young for my age, having been born
into a family the generally lives to be old. My parents both lived to be 90,
my maternal grandfather lived to be 95, and my maternal grandmother was one of
three in here family that lived to 100+. On my father's side, his mother died
at 88. For someone born in 1890 that was a feat. His father committed suicide
during the great depression, but two of his father's sisters lived to 98 and
101. You get the drift. Dinosaurs. But wear and tear still took their toll. My
father's hearing was week, and he was losing his eyesight before he died. My
grandmother was completely blind before she died. My mom succumbed to a cancer
that had recurred.

Wear and tear.

I worked outdoor physical labor through high school, and I have the moles and
other skin issues related to excessive sun exposure. I also have several
joints that were injured then that have caused problems my whole life. I lost
much of my hearing to childhood illness before I was twelve (an misdiagnosed
issue that would have been malpractice in today's environment) that I followed
up with too much live music, operating heavy machinery, and shooting trap.

Wear and tear.

So maybe we can extend the healthy life of our organs, but that isn't going to
magically make injuries go away.

And I am not suggesting that young people should ever listen to people in
their sixties, I certainly never did, but if you can avoid damaging your skin,
hearing, and joints while you are young, you will live to appreciate that.

------
Gatsky
Hmm. Well the epigenetic aging clock effects are hard to interpret, but they
also show recovery of cognitive performance in aged rats treated with their
magic plasma fraction. That is kind of exciting.

Nevertheless, there are significant conflicts of interest going on, so
confirmatory studies by independent bodies in animal models are required. Then
there are the human studies. They obviously want to use the epigenetic clock
as a surrogate endpoint in humans, so the trial can be completed in a short
time frame. Not sure about that, this is a fairly complicated surrogate
endpoint we are talking about. Some more relevant biomarkers of aging in
humans which incorporate functional readouts would be required at the very
least.

[https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1....](https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full.pdf)

------
curiousgal
Age reduction.

Enammel reconstruction.

Batteries.

The three pillars of perpetual breakthroughs.

~~~
gameswithgo
Since 1990 the energy density if lithium ion has has increased by a factor of
about 4, and the cost had reduced by a factor off about 6. While keeping in
mind that consumer lithium ion itself was quite a breakthrough in terms of
energy density in the first place.

Both of these metrics are still improving too.

~~~
JoshuaDavid
I dunno about enamel reconstruction (though I was under the impression that
materials used to _replace_ tooth enamel have gotten enormously better in the
last few decades to the point where your fillings will wear down slower than
your teeth), but life expectancy has also been slowly increasing over the past
few decades, and a significant fraction of that comes from people staying
relatively healthy for longer.

------
garyclarke27
Seems very exciting - I have huge respect for the author of this blog Josh
Mitteldorf (he’s a genius) - so fingers crossed - they may be onto something
real. Plasma from young donars is already proven to be beneficial to elderly
recipients - this appears to be an extension of such research.

------
eternauta3k
I'm dimly aware that issues with rat models for aging were pointed out by Bret
Weinstein. Any comments on that?

~~~
spacephysics
I recall it had to do with telomere length in mice, and how longer telomeres
were involuntarily selected for when breeding lab mice [0]

[0]
[https://pubmed.ncbi.nlm.nih.gov/11909679/](https://pubmed.ncbi.nlm.nih.gov/11909679/)

------
JoeAltmaier
I'm uneasy - this reads exactly like a snake-oil pitch. What next? Spas that
supply plasma injections?

------
mkchoi212
Very promising results! But I would love to see what happens when this is
approved for human subject testing. Let’s see if the magic number of
injections needed - 4 - is still the case.

~~~
ctack
I read that as four per rejuvenation with no word about how often a
rejuvenation would be needed.

------
tim333
Some details:

>18 rats were divided into three groups. 6 young rats (30 weeks old), 6 old
rats (109 weeks old) & 6 old rats (also 109 weeks old) treated with plasma
fractions from the young rats.

>Plasma fraction treatment consists of two series of IV injections, four times
on alternate days for 8 days. A 2nd series of injections were given 95 days
later. In its entirety, the experiment lasted 155 days.

>Blood was drawn at regular intervals for analyses to monitor the impact and
cognitive functions were assessed 4 times. DNA methylation profiles of several
organs were generated and age was calculated using six epigenetic clocks.

>Using the final versions of their epigenetic clocks the reversal was: liver
75%, blood 66%, heart 57%, hypothalamus 19%. Average rejuvenation across four
tissues was 54.2%.

Source some David Sinclair tweets (more in there)
[https://twitter.com/davidasinclair/status/125991292869585715...](https://twitter.com/davidasinclair/status/1259912928695857152)

------
ve55
As much as these things are very speculative, that is the necessary direction
that we have to go in in order to maximize the chance of actually finding and
then using these breakthroughs.

The only way to actually make significant progress in an area this difficult
is to constantly be looking for answers everywhere we can.

------
andy_ppp
Vampires have been doing this for millennia right?

Seriously though, does putting Tom Hanks’ blood plasma into a young
coronavirus nurse age them a little bit? Does the effect work in reverse?

(Just to explain the above Tom Hanks had Covid and gave plasma in a
convalescent serum).

------
Invictus0
Does this lend credence to the idea that blood transfusions from young people
could make one healthier or extend one's life?

~~~
logfromblammo
Yes, it does.

The hypothesis is that "clock molecules" in the bloodstream provide a global
age-clock for about five other tissue-specific age-clocks in the body.
Spoofing the global clock signal for a long enough period tricks the subsystem
clocks into thinking they are younger than they really are, including the
native global age-clock mechanism.

Completely replacing your own blood with a young person's blood, repeating if
necessary, would also accomplish the same trick, more expensively.

The real question is whether old tissues can function like young tissues when
tricked into trying.

------
rlucas130
There was a great sci-fi book (imho) by Robert J. Sawyer that posits the use
of nano-tech to enable age reduction called Rollback
([https://en.wikipedia.org/wiki/Rollback_(novel)](https://en.wikipedia.org/wiki/Rollback_\(novel\))).
This just made me think of that book.

------
lawrenceyan
It's impossible for an old cell to become young again, at least with our
current level of technology, because that would require you to reverse all the
mutations that have built up over time in that cell. If your argument is that
our bodies have many different repair mechanisms, and that as long as we can
figure out how to activate them properly, we can then reverse aging, I would
caution you that while you're correct in that repair mechanisms do exist, it's
important to remember that these mechanisms are themselves composed from the
same components as the rest of your body, i.e. they too will age and begin to
fail over time.

The only way to actually cure aging would be to develop sophisticated enough
outside mechanisms that would be able to intervene and replace these
biological mechanisms as they fail. Macro level replacements won't cut it
either. Replacing an organ might give you a few years here or there, but it
doesn't address the issue that aging fundamentally happens at a molecular /
atomic level.

~~~
pmiller2
> It's impossible for an old cell to become young again, at least with our
> current level of technology....

Depending what you mean by "become young again," that's not true. See
[https://med.stanford.edu/news/all-news/2020/03/old-human-
cel...](https://med.stanford.edu/news/all-news/2020/03/old-human-cells-
rejuvenated-with-stem-cell-technology.html) The problem here is scaling this
up beyond tissue cultures.

~~~
lawrenceyan
Again, I emphasize this point:

> I would caution you that while you're correct in that repair mechanisms do
> exist, it's important to remember that these mechanisms are themselves
> composed from the same components as the rest of your body, i.e. they too
> will age and begin to fail over time.

The process of nuclear reprogramming to induced pluripotent stem cells, which
is the subject of your referenced paper, is something that I believe to be a
great scientific breakthrough, but nevertheless fails to address the
accumulated mutations that build up over time in your cells. All those
mutations don't just magically disappear.

~~~
pmiller2
Sure, but, presumably, in most cases, you can repeat the therapy. And, if such
treatments are shown to provide additional healthy years, who cares, even if
they're not repeatable? I'd pay for a treatment that could be shown to add
years to my life expectancy.

~~~
lawrenceyan
There are drawbacks that you should consider. Many of the repair mechanisms
that exist, which later on become deactivated, are turned off for a reason.

It's important to understand that renewed growth is synonymous with cancer.
The older you are, the greater the risk you face as your fail safes and
redundancies begin to fail from corruption due to accumulated mutation. It's
often better to completely turn the thing off, which is exactly what your body
does, after a certain point.

The older you get and the more you age, the more you should focus on
preventing the development of cancer over anything else as that will likely
have the greatest impact in determining your life expectancy, assuming you
continue to stay active, eat properly, and get enough sleep.

------
nil-sec
Are there no people who have to receive regular blood donations? Would you not
notice such an effect in these people? I guess the donors are probably not all
younger than the receiver but on average this is probably true. Does anyone
know of a subpopulation that might qualify?

------
snvzz
It's worth remembering there's an engineering-approach to undoing aging
damage, and a foundation[0] dedicated to advancing this approach.

[0]: [https://www.sens.org/](https://www.sens.org/)

------
virajgite
Here's an excellent video on the same topic that discusses David Sinclair's
research [https://youtu.be/XlFl0jDg0Jg](https://youtu.be/XlFl0jDg0Jg)

~~~
Rury
I like his interview here:
[https://youtu.be/IEz1P4i1P7s](https://youtu.be/IEz1P4i1P7s)

Granted I'm not completely sold on the supplements quite yet.

~~~
tim333
I was impressed by that interview and am thinking of trying the supplements a
bit to see if they do anything.

This article was jolly also
[https://www.bostonmagazine.com/health/2019/10/29/david-
sincl...](https://www.bostonmagazine.com/health/2019/10/29/david-sinclair/)

------
henearkr
I'm very curious about how this mere signaling solves all off once:

\- natural as well as stress-induced telomeres shortening

\- oxidative molecular stress

\- accumulative viral damage on body's DNA

\- natural atrophy of thymus (thymic involution)

etc

I'm curious about the proposed mechanisms, if any.

------
fallingfrog
Aw, I was hoping for something a bit more substantial here. I think the sens
foundation is on the right track but this is a highly implausible approach
(though I am not a biologist).

------
im3w1l
So, do you become chimeric by doing this? Beating death Ship of Theseus style?

------
dntbnmpls
We could also look into whether holocaust survivors share a genetic,
pyschological, etc predisposition which allows them to live longer than native
born israelis. Certainly there must be a will to live/survive but also a
genetic/biological aspect which helped them survive starvation, disease,
deprivation and thrive afterwards.

[https://www.haaretz.com/israel-news/.premium-holocaust-
survi...](https://www.haaretz.com/israel-news/.premium-holocaust-survivors-
live-longer-than-native-born-israelis-1.6822053)

------
rootsudo
This is really interesting, thank you for posting. :)

------
Koshkin
But as always, there must be a katch.

------
Koshkin
But aging, followed by death, is important. And not just for the biological
evolution, but also for social progress. Besides, lifespan is measured not in
years or the total length of the spaghetti consumed but in memories and
accomplishments. So, I am not sure what exactly is the point of trying to
extend human biological lifespan. There were people that in 30 years had
accomplished more than other would not be able to in however many years would
have been given to them.

~~~
frenchie4111
It seems important to our current society because it is a pillar, or a given,
to how society runs today. It is almost impossible to imagine a society
without aging. If/when that day arrives, I am sure it will seem a lot less
important.

------
meiraleal
The laziness of believing that we are going to have a rejuvenation pill in the
future is a big scam/joke. Just like pills to recover from baldness. Most
people are running on 10, 20% of their full healthy, no pills are never going
to change that. Not even a weight reduction pill will help the ones who wants
to still be able to eat junk food and drink soda.

------
ryanmarsh
_Crucially, plasma treatment of the old rats [109 weeks] reduced the
epigenetic ages of blood, liver and heart by a very large and significant
margin, to levels that are comparable with the young rats_

Since I spend a lot of money on this kind of stuff I figured I'd share. The
use of platelet rich plasma (PRP) is rapidly growing in the beauty industry.
My wife has had PRP used in various procedures that have indeed created a more
youthful appearance (by like 10 years). Basically they can inject it anywhere
through hundreds of tiny needles. Most often this is done to the face but you
can even do this to the vagina (you'd be surprised how many women over 40 do
this). That is, if you want hundreds of needles entering the labia and (horror
of horrors) the clitorous too.

There's even a process for men where you can have PRP injected in your shaft
and the results (I'm to terrified of needles in my dick to try it) are quite
good (firmness, sensation, youthfullness) from what I hear.

The PRP procedures my wife has had, although expensive, have had impressive
results.

~~~
zarkov99
I hope you are not just trolling. I am not sure if I enjoy more the news that
there are effective treatments against aging or the rage you are going to
induce with this post.

~~~
ryanmarsh
Google "vampire facial" and I can tell you from personal experience the
results are impressive beyond anything else I've paid for my wife (laser
facials, botox, fillers, lip injections, etc...).

I don't understand what the "rage" would come from, or why it's "pot". This is
available today, and many people pay for it. The results speak for themselves.
People who pay for this stuff don't make a habit of talking about it. I'm
going to guess by your comment that you're not as beauty focused as some other
people. For beauty focused individuals this is serious business. Ever wonder
why your favorite actress over 50 "hasn't aged" past 35? It's not just plastic
surgery or makeup. This is how many people make a living in industries where
looking old is not rewarded.

~~~
zarkov99
Pot was a typo for post, sorry about that. The rage would come from people who
feel that any indulgence accessible only to those richer than themselves is an
outrage. There are many such people in tech circles.

~~~
ryanmarsh
That seems like at least half of HN.

