
What Doesn’t Kill Me Makes Me Stronger - Multics
http://joshmitteldorf.scienceblog.com/2014/12/09/what-doesnt-kill-me-makes-me-stronger/
======
TylerJay
I'm not buying the Demographic Theory of Senescence.

> Aging is nature’s way of leveling out the death rate, assuring that we don’t
> all die at the same time. Aging puts our deaths on an individual schedule so
> we can die at different times; other causes of death tend to kill everyone
> or no one.

It's a magical "group selection" hand-wavy argument—it sounds nice and is kind
of heart-warming, but when making an evolutionary argument, that's usually a
bad sign. In this case, it doesn't provide an explanation of how purposeful
aging could possibly increase an individual's probability of passing on their
genes.

If not aging was an option, you would expect to see something more similar to
the results of Michael J. Wade's 1976 experimental attempt to show group
selection behavior in individuals of a species. He artificially induced
resource constraints on a selected subpopulation of flour beetles to see if
the beetles would restrain their reproduction for the benefit of the group.
What happened? The adults started eating the young of the other adult beetles.

[http://www.pnas.org/content/73/12/4604.full.pdf](http://www.pnas.org/content/73/12/4604.full.pdf)

I don't have an explanation for aging, but I seriously doubt that it's a way
for Nature to regulate population size to avoid resource depletion for the
group.

~~~
soneca
I'm way out of my league here, but what if aging is just the way to evolve and
adapt. If there were no natural deaths, beings with the same genes would be
around forever, with no possibility for its species to adapt to a new
environment.

Any reproduction would be just creating more competition for resources if one
expect to live forever. So there would be no deaths, but also no births, no
mutations.

If there was no death we still would be just - what is the first life form to
age? protofishes? populating the oceans until the salinity (?) changes and we
were all dead.

~~~
drcomputer
Yea, coming from the background assumption of "everything comes from the same
thing", it seems more interesting to me that we have consciousness to
experience, rather than the curiosity that we age and die. Age and death are
phenomena we observe of ourselves, a thing that is constantly changing yet
fundamentally the same thing.

It's a philosophical quirk, but it really depends on your existential and
universal (philosophies / beliefs / religions). Things you must assume,
basically, in order to make meaning from what is otherwise, pure logic
(structural arrangement) and pure state (instances of that structure).

The idea that aging and death are undesirable is a complex phenomena to begin
with. A rock does not care that the water slowly washes it away to shape it
into a new form, yet humans have very discerning opinions on the matter across
all phenomena they observe. Every explanation humanity manufactures seems to
have some bias.

~~~
Umn55
>it seems more interesting to me that we have consciousness to experience,

Everything that is alive has some level of "consciousness" aka some ability to
sense, detect, and adapt to it's environment. The idea that consciousness is
"special" and "unqiue" is the big lie. If knowledge is unified, then that
means the same is true for the universe, since what we call "knowledge" is in
fact the universes structure directly. Like your hand, your car, etc. What we
call "knowledge" is our representations (symbolic languages like math,
english, etc). We confuse our symbols with reality.

It's not that knowledge is "provisional" (aka the structure of the universe is
the truth, hence not provisional), it's that our current abstract
representations of it is.

------
Tossrock
There are some questionable assertions in this article. eg,

"Survivors of the Hiroshima and Nagasaki bombings had lower cancer rates later
in life than people of similar age who had not been exposed to radiation " has
the ref
[http://informahealthcare.com/doi/abs/10.1080/095530006010859...](http://informahealthcare.com/doi/abs/10.1080/09553000601085980)

which a) has nothing to do with Hiroshima or Nagasaki, and b) found that low
dose radiation in fact increased cancer risk (shock!):

"The results suggest that prolonged low dose-rate radiation exposure appeared
to increase risks of developing certain cancers in specific subgroups of this
population in Taiwan."

~~~
hollerith
Also:

"Paraquat is the chemical name for the active ingredient in Agent Orange."

In reality, paraquat is very different from the active ingredients in Agent
Orange (2,4-D and 2,4,5-T).

For instance, a molecule of paraquat contains 2 nitrogen atoms and no oxygen
atoms whereas a molecule of 2,4-D or 2,4,5-T contains no nitrogen and 3 oxygen
atoms.

The only similarity between them that I know of is that they are both used as
herbicides.

~~~
deciplex
The author seems to be confusing the US government's use of agent orange in
Vietnamese jungles, with their use of paraquat on marijuana farms in Mexico in
the 70s.

------
exratione
Mitteldorf has an interesting take on programmed aging, which is to say the
collection of theories suggesting aging is a evolved program that acts to
shorten life because there is some very global selection advantage in it. It
is worth reading as a counterpoint to the more common viewpoints of that
school (such as the hyperfunction theory of aging that is a modern take on
antagonistic pleiotropy in the context of programmed aging) espoused by some
of the Russian gerontology community. There's a link somewhere in the article
linked above.

Programmed aging is, however, a minority view in the aging research community
as a whole. The consensus view is that aging is caused by an accumulation of
unrepaired damage, though there are many factions and a lot of debate within
that tent. Programmed aging seems to be gaining some ground, but it's rather
hard to tell from the sidelines as some of the advocates (e.g. Blagosklonny
and his views on mTOR) are very prolific in their publications.

Hormesis as a phenomenon to be measured and evaluated can stand apart from
either of these views on aging for the purposes of evaluation and
investigation of molecular mechanisms. It is a robustly demonstrated thing in
animal models, though as for all these things translating those findings into
human health is ever a challenge. For things like calorie restriction,
exercise, and intermittent fasting, where hormesis is thought to play an
important role, the human and rodent responses in the short term are very
similar. There is a small mountain of papers on this topic - just go look at
PubMed and search for hormesis and longevity.

Hormesis works because some forms of damage - such as mild oxidative stress -
trigger repair responses that last long enough and are proficient enough to
produce a net benefit in cell health throughout tissues. There is a dose-
response curve to all of this of course. This is may be how you get a variety
longevity mutants in nematode worms wherein they live longer if you either
reduce or increase the flux of reactive oxygen species emitted from the
mitochondria. Less means less damage and more means less damage because it
produces more aggressive repair.

There are plenty of ways to damage tissue that will cause incremental damage
over time, but are not hormetic, and will not produce benefits. It all depends
on how the repair mechanisms handle the specific case in question.

------
jmnicolas
I had a friend who was telling everybody : "what doesn't kill you makes you
stronger ... or paraplegic" and it made him laugh every time.

This title made me think of him, I automatically appended "or paraplegic" to
the title.

RIP M.

~~~
ta75757
I used to say something similar until I read an even better version:

"What doesn't kill me makes me stronger."

"I hope a bus tries to make you stronger."

(source:
[http://thelastpsychiatrist.com/2013/09/how_does_the_shutdown...](http://thelastpsychiatrist.com/2013/09/how_does_the_shutdown_relate_t.html))

------
george_ciobanu
I'm sure your sources are correct but the view and sample data are biased.
Cancer rates, as you note, go up with radiation and also withUV exposure. You
make a dangerous point that some people who don't read carefully might buy
into fast and make poor decision. A warning at the top of the post or another
analysis of the effects of these exposures, on a large sample that also
presents the downsides would be more balanced.

------
cnlwsu
Hormesis as a general concept reeks of me of the "like cures like" of
Homeopathy. This is mentioned in the article even. "A little snake venom is a
cure to snake venom" is commonly used when explaining homeopathy. There may be
some scenarios that exhibit this behavior but it still means your relaying on
a fallacy of composition to turn it into something that can be sold as a life
style.

Why do we have to simplify things and try to apply sweeping generalizations?
The universe is complex. Things that apply one way to somethings do not apply
that way to others.

~~~
titanomachy
Yeah but this concept isn't nearly as hard to stomach for me. "Fighting off
disease makes you better at fighting off disease" is a little more believable
than "these overpriced water molecules can learn the shape of toxins and help
eliminate them in your body".

------
abandonliberty
A lot of this makes sense in the new deterministic model of aging.

It argues that aging is not a collection of mutations, the old/popular model,
but instead a programmed outcome of our genes that never experienced selective
pressure.

We are like a building, but the builders never know when they are done and
eventually start doing counterproductive work that destroys us.

Kicking in a response to injury or pathogen may cause cells to run programs
that are less detrimental to our continued survival.

Edit: Let me clarify that this in no way should be taken as an endorsement of
the author's claims. I have proposed a possible model that would make the
claims reasonable, but haven't examined them closely. There is a lot of
quackery out there.

~~~
scotty79
The only reason why we are here and not rotting are our immune systems. Take
it away and we dissolve in matter of days.

Recently research on very old lady showed that all of her immune cells came
from just a handful of stem cells.

It made me think that the only reason we live that long is because, that's how
long our immune system lives. As we grow old it becomes less and less
versatile as stem cells die out and less effective as the most effective
randomly die out. Then the old age diseases kick in as there's less and less
competence in cleaning up this pile of bio-matter that we are.

Excising and eating a little is not because it almost kills us and therefore
it makes us stronger, just because our cleaning crew was optimized for much
less food and much more movement.

Stress is not good for you. When you see pair of identical twins you can tell
which one lived life of more stress. He/she looks older and by various
measurements is older.

------
lkrubner
I think aging, in vertebrates, is mostly driven by the need to preserve what
data has been encoded in the nervous system.

Ask yourself these questions. Would you rather have old bones or young bones?
Would you rather have an old cardio-vascular system or a young cardio-vascular
system? Would you rather have old muscles or young muscles?

In every case, the answer is "young".

But would you rather have an old nervous system or a young nervous system? The
old nervous system is trained, the young one lacks all skills (skills range
from the basics, like control of urination and defecation, to knowing how to
hunt down an antelope).

Creatures that do not have a trainable nervous system (trees, coral, insects)
experience a very different aging process.

Among vertebrates, those creatures that demonstrate negligible senescence
(tortoises) also demonstrate a lack of learning. The price of immortality is
perpetual immaturity of one's nervous system.

------
noonespecial
Sounds like a wind up for one of Garry Trudeau's characters from back in the
day...

[http://en.wikipedia.org/wiki/Mr._Butts](http://en.wikipedia.org/wiki/Mr._Butts)

------
rdlecler1
To quote Dobzhansky, this is all becomes obvious in the light of evolution. A
challenging environment removes those cells that accumulate mutations. (i) In
challenging or resource constrained environments mutated cells tend to behave
more aberrantly and our immune system responds by attacking them (this is why
radiation therapy works). (ii) Mutated cells will be more prone to pathogenic
infection. In either case, we use the external world as a kind of extended
immune system or to police our bodies against cellular mutiny.

~~~
mitteldorf
There is no "natural selection" within an individual body, within an
individual lifetime. Yes, there are some cells that continue to live and
others that continue to die. But the cells are not competing, with the fittest
winning out. Rather the whole scheme is orchestrated centrally for the good of
the genome (which is the same in every cell).

~~~
rdlecler1
Actually it's called somatic evolution. And there is no central orchestration.
When cells start to mutate they no longer share the same genome and it's
typically in the organism's interest to remove those cells because they can
lead to mutation.

------
ytturbed
>If animals eat all the food that is available to them and reproduce as fast
is they are physically capable, then the environment will be denuded, the next
generation will starve, and the species will face extinction. All animal
species are evolved to avoid this

Isn't this a Tragedy of the Commons? Won't genes that cause individuals to eat
more and reproduce more quickly than fellow members of their species confer a
relative advantage causing those genes to spread through the gene pool?

~~~
mitteldorf
Tragedy of the Commons is exactly right. Yes, the genes spread through the
gene pool, but then the population goes extinct very quickly because there's a
huge population and nothing to eat. This is the most powerful form of group
selection, and it was first described by Michael Gilpin,
[http://press.princeton.edu/titles/663.html](http://press.princeton.edu/titles/663.html)

------
ajcarpy2005
This is all based on the ability of the organism to strongly adapt. In order
to do this, they need enough energy (calories) and micronutrients. I assume
the organisms studied in labs for the ability to adapt to these stressors, are
(outside of calorie restriction or related studies) well-fed...

Humans are often not so well-fed, at least not nutritionally.

------
deepakjc
A very interesting concept, will definitely need to read more on this!

But what about the kind of research that talks about the dangers of living in
cities... like "living in a polluted city is like smoking X cigarettes a day"?

------
scriptman
This sounds a lot like Taleb's Antifragile:
[http://en.wikipedia.org/wiki/Antifragile](http://en.wikipedia.org/wiki/Antifragile)

~~~
Udo
In reality it's the other way around: Antifragile sounds like a lot of
principles in nature, or rather: observations about nature that have been made
a long time ago. However, this article sounds scientific but really isn't, as
others in this thread have already pointed out.

------
deepakjc
If this is true... then I need to rethink a lot of my life choices... what is
actually good for me?

Would love to hear the opinion of doctors/scientists on this...

~~~
Qwertious
I would be very, VERY sceptical - the moment he brought in evolution, he
argued a theory based on (and nigh-identical to) group selectionism. Except
group selectionism has been thoroughly debunked, to the point where he might
as well have been spouting Lamarckism - read "The Selfish Gene", by Richard
Dawkins.

Put simply, you can't just jump from looking at individual survival to looking
at a group's survival, because any individual could just be a free-rider. More
importantly, what's actually been _observed_ is that group selectionism simply
doesn't happen in the real world.

So while anything I said about the rest would be mere opinion, there is at
least one multi-paragraph section of his argument that is a GIANT heap of
shit.

~~~
mitteldorf
The Selfish Gene was a phase in our understanding of evolution. The mainstream
now agrees that evolution is a whole lot more complicated than that. It's
still true that "group selection" is a dirty word to a majority of
evolutionary scientists, but this is shifting pretty fast - much less true
than it was 10 years ago. Take a look at the works of David Sloan Wilson. I
recommend his book, Unto Others.
[http://www.hup.harvard.edu/catalog.php?isbn=9780674930476](http://www.hup.harvard.edu/catalog.php?isbn=9780674930476)

------
Madmallard
Yeah... what about bacteriocidal antibiotics that cause mitochondrial DNA
damage? The people affected by that stuff don't seem to just like recover and
get stronger.

~~~
fasteo
Mitochondrial damaged human speaking (genetic cause, not antibiotics)

Hormesis is about dose. In these cases, the dose is just too high and our body
is unable to cope with it.

In my case the damage is just below this threshold and my body has created a
powerful antioxidant machinery [1] that is keeping me alive. In other cases of
my disease, the burden - % of mutant mitochondria - is just too high [2] and
sadly, the kids die when they are 3-4 years old.

[1]
[http://www.sciencedirect.com/science/article/pii/S1096719203...](http://www.sciencedirect.com/science/article/pii/S1096719203001677)

[2] [http://ghr.nlm.nih.gov/condition/leigh-
syndrome](http://ghr.nlm.nih.gov/condition/leigh-syndrome)

------
pdkl95
Trevor Goodchild (AEon Flux) had a far better version: "That which does not
kill us, makes us _stranger_."

------
michaelochurch
I'm very skeptical.

Aging isn't there because our genes "need" it. It's there because our genes
_don 't need_ long lifespans. The gain in reproductive viability that we'd get
with a >60 year natural lifespan just isn't enough to justify the constraint
that a much longer (or indefinite) lifespan would impose on our genetic
"search space". We can live forever and be simple, or we can be complex and
get a job done and die.

There probably is some anti-fragility in us. I don't buy the LNT threshold of
radiation, for example. All that said, I'm not sure that hormesis is useful as
a general concept. There are mild stressors (such as cold, when prepared and
for short duration) that turn out to have positive effects, but there are a
great number of stressors that seem to have no positive effects, whether
you're talking about biological agents (e.g. cadmium, lead) or psychological
experiences (e.g. rape, war).

~~~
dvanduzer
Can you translate that for someone who skimmed to "weight on belly versus
weight in backpack" ?

~~~
thret
Natural selection only molds us up to the point where we procreate and ensure
the survival of our offspring. After that (say age 50), we're winging it.

Mild stressors that would occur naturally - physical exertion, exposure,
hunger; it is perfectly logical that natural selection would favour those who
handle these circumstances well.

~~~
ak39
I like that ... "winging it" after 50. :-) Made me chuckle. I agree with it.

I have a (an emotional) problem with that number though, being acutely aware
and sensitive to ageism or age-related relegation of human functions and roles
in society. I have a problem with any number for that matter. 50 is too low,
and any number will always be too low, the way I see it if you incorporate
Dawkins' idea of the Selfish Gene into the mix. I would argue that sticking
around "to ensure the survival of our offspring" (as you put it) for the human
species is significantly more important than any other species on the planet.

Turtles don't need this survival strategy. Lay eggs (procreate) and chuck -
that form of hormesis aggressively weeds out the weak members of the species
from the ones laying eggs for the next generation. While chimps, elephants and
whales may also need to "stick around longer" for their young - relatively,
the human is by far an incredible outlier in this regard. Not only do adults
have to stick around for their kids well into the young's teen years, but
elders too have to stick around for the group or for the clan. This last point
is important to understand the relationship between the survival success of
the species and an imagined age cutoff for "usefulness" (that contributes to
the success of the species) of any one member of the species. The individual
has extended roles beyond just his/her offspring. His/her role in the clan's
survival success mattered too.

Recent discoveries of hominid fossils suggest that as early as Erectus,
"humans" have been keeping their elders alive! :-) Evidence of a toothless
skulls suggest that able members of the group may have been keeping the elder
alive by chewing for her. But for what?? Could it be to access knowledge of
poisoned berries to avoid, or hunting methods to teach or ... stay at home
creche for the kids while able-bodied adults went out for hunting??

Again, I don't think I needed to respond to your point necessarily ... you're
right for the most part.

~~~
pavel_lishin
> 50 is too low, and any number will always be too low, the way I see it if
> you incorporate Dawkins' idea of the Selfish Gene into the mix. I would
> argue that sticking around "to ensure the survival of our offspring" (as you
> put it) for the human species is significantly more important than any other
> species on the planet.

I see what you mean, but with every generation of your offspring, you're less
and less vital to their survival - your children and grandchildren can care
for your great-grandchildren as well; there's more redundancy there, so no
individual is as crucial.

------
tokenadult
Searching for articles with the keyword "hormesis" (a word I first learned in
the latest book by Nassim Nicholas Taleb, who is not a person with medical
training or experience) on the Science-Based Medicine website is
instructive.[1] The concept of "hormesis" is not well thought out enough or
well validated enough with careful measurements to be your guide to your
personal health practices. There is better health advice in some of the
earlier comments here.

Thank you to the several commenters who have already politely pointed out
factual and logical mistakes in this submission. We can do better for reading
matter to be submitted to Hacker News. "Essentially there are two rules here:
don't post or upvote crap links, and don't be rude or dumb in comment
threads."[2]

[1]
[http://www.sciencebasedmedicine.org/?s=hormesis](http://www.sciencebasedmedicine.org/?s=hormesis)

[2]
[https://news.ycombinator.com/newswelcome.html](https://news.ycombinator.com/newswelcome.html)

~~~
Multics
> Searching for articles with the keyword "hormesis" (a word I first learned
> in the latest book by Nassim Nicholas Taleb, who is not a person with
> medical training or experience) on the Science-Based Medicine website is
> instructive.

No it's not! 3 out of the 7 links relate to homeopathy, which the article
_explicitly_ states is problematic:

'Association with the problematic science of homeopathy. In the early 20th
Century, people who promoted homeopathic medicine were prominent supporters of
the concepts of hormesis.'

Your stance is based on an _argumentum ab auctoritate_. How about constructing
an argument, rather than spewing meta-trash talk?

> a word I first learned in the latest book by Nassim Nicholas Taleb, who is
> not a person with medical training or experience

Ergo, hormesis does not exist? _Non sequitur_.

> The concept of "hormesis" is not well thought out enough or well validated
> enough with careful measurements to be your guide to your personal health
> practices. There is better health advice in some of the earlier comments
> here.

The only _prescription_ of the article was to eat less & exercise more!

> Thank you to the several commenters who have already politely pointed out
> factual and logical mistakes in this submission.

Agreed. It's called 'discussion'.

> "Essentially there are two rules here: don't post or upvote crap links, and
> don't be rude or dumb in comment threads."

I don't see how this quote is relevant.

