
There's no limit to longevity, says study that revives human lifespan debate - mrfusion
https://www.nature.com/articles/d41586-018-05582-3
======
WhompingWindows
The Italian study argues after a certain threshold age, lets say 105, Italians
hit a constant, "mortality plateau, which was 50:50 odds of living to your
next birthday, and thus since mortality is not increasing year on year,
theoretically there is no upper bound on the age of a person. This may be true
theoretically, but mathematical reasoning clarifies this somewhat. Even if you
have 1 million humans aged 105 right now, which is probably a vast
overstatement, they would diminish to 100,000 humans in less than 4 years,
then diminishing to 1,000 humans aged 115 in 10 years' time. After this point,
it's basically a question of statistics, as we keep halving the population
yearly and get into statistically unsubstantial cohorts of humans. So, while
it may be that some humans could live to 130-140 naturally, without fountain-
of-youth innovations, the VAST majority of us will die much, much earlier.

The low-hanging fruits of obesity, heart disease, and diabetes are calling to
public health far more urgently than this pie in the sky limitless life.

~~~
EamonnMR
Humans have a 1/3 lifetime cancer risk, and I suspect it will go up if we
extend lifetimes. It's a wall to longevity. If we get past that wall, there's
still proteopathys. There's no real approach to curing those yet (at least not
that I'm aware of.)

~~~
JamesBarney
Why do you think cancer is undefeatable? The risk of cancer rises
substantially with age, and much of the increase in risk is probably due to
the immune system malfunctioning.

~~~
EamonnMR
We aren't there yet.

~~~
ethbro
[http://www.latimes.com/science/sciencenow/la-sci-sn-
breast-c...](http://www.latimes.com/science/sciencenow/la-sci-sn-breast-
cancer-immunotherapy-20180604-story.html)

Oncology + new genetic tools (just sequencing, not even CRISPR/CAS9) is making
amazing progress.

Things that would have been a death sentence 20 years ago now have reasonably
hopeful mortality rates.

------
codingdave
So biologists say there is a limit. But if you only look at the statistics
from extreme examples of people over 105, mortality looks flat for a few
years, so statisticians say we can live forever.

Is it just me, or is this just bad logic?

~~~
bcheung
It's bad logic and bad journalism.

People have a 50% chance of dying each year over 105 translates to there is no
limit to longevity?

Also, the critic in me makes me want to see the actual distribution because I
would think there is a tail effect going on and a small group of people are
just genetically living much longer.

~~~
bthornbury
My interpretation:

Death rates increase every year due to naturally occurring mechanisms in the
body. Consider those mechanisms as a function with the body as a parameter and
the output as a more aged body (or rather a body with higher probability of
failure).

If the body reaches a point where the death rate ceases to increase year per
year, it would suggest that those same naturally occuring mechanisms, thought
of as a function, approaches some asymptote.

Note this doesn't necessarily mean you stop aging (in appearance), just that
your body's rate of failure no longer increases. This suggests that if the
reasons for failure can be treated properly, perhaps the body can remain in
that equilibrium state indefinitely.

This study provides some preliminary evidence that such an asymptote may exist
in the body's natural mechanisms. Both controversial and exciting. Worth
exploring further.

~~~
ethbro
Exactly. And the really cool thing is "Why?"

Because there are essentially two things that kill you. Either you die of
something you get, or you die because your body wears out (as others have
pointed out, we know body systems wear and become less effective with aging).

Therefore, _if_ mortality stops _increasing_ with respect to age at a certain
point, but we know the body is accumulating additional wear that makes it less
resilient, there must also be a corresponding _decrease_ in mortality risk
with respect to random things killing you.

So essentially, if you're 100 already... you might have a statistically
smaller risk to die from heart disease, cancer, etc than someone who is only
92.

~~~
Guest9812398
> Therefore, if mortality stops increasing with respect to age at a certain
> point, but we know the body is accumulating additional wear that makes it
> less resilient, there must also be a corresponding decrease in mortality
> risk with respect to random things killing you.

Agreed. I assume older people are receiving higher levels of care, and
therefore have a lower risk of dying from random things.

For example, someone age 100 has a small chance of falling and receiving a
life threatening injury when they go to get a glass of water from the kitchen.
Someone age 115 might have a smaller risk, because they're more likely to be
in a wheelchair, and therefore will not stumble and fall. Do they need to
change a light bulb? The 100 year old might try to stand on a chair and risk
falling. The 115 year old will probably have full-time care, and push a button
to alert someone else about the light bulb. Older people usually travel less
often, so their chance of dying in a car crash starts to decrease. They're no
longer diving with sharks, so shark attack deaths decrease. They're less
likely to be outside in a thunderstorm, so lightning related deaths decrease.

Some of those examples are a little silly, but I think the idea is right. When
you go from 100 to 115, you decrease your risk of dying from random things
(usually because you're no longer doing those things), but you increase your
risk of dying from age related factors. These two cancel each other out, and
the chance of dying on any given year appears equal. This would mean the study
is wrong, and there is a limit to longevity.

------
jkingsbery
A 50% mortality rate per year translates into there being a <0.1% chance of
living for 10 years. How does that translate into there being "no limit to
longevity?" I seriously don't get the claim.

~~~
tpeo
It means that mortality rate doesn't approach 100% around some given age,
which would be the hypothetical biological limit. I don't see the issue.

~~~
repsilat
Right. "You don't get worse at living after a certain point." Sounds like big
news to me even if the "half life" was shorter.

------
visarga
As we live, we forget stuff, we change, the situation around us changes. So
it's as if we gradually die every day, to be replaced with a new self. The day
we physically die is just the last time we die. Not to mention that we
experience nothingness and coming back every night.

By analogy, is a continually trained neural net the same as a previous version
of itself? Is it a different one, especially after a long time? Did the old
version end/die by continuous accumulation of changes?

~~~
newman8r
Reminds me of the ship of Theseus
[https://en.wikipedia.org/wiki/Ship_of_Theseus](https://en.wikipedia.org/wiki/Ship_of_Theseus)

------
bloak
I would have thought it's intuitively obvious that there's "no fixed limit on
human longevity", and it's therefore obvious that mortality "flattens out":
how else could it avoid going over 100%? It presumably is possible to say
something interesting and non-trivial about the shape of the curve but it
seems to be beyond the mathematical competence of the people writing these
journalistic reports to do so.

Looking at the Wikipedia list of longest-lived people
([https://en.wikipedia.org/wiki/List_of_the_verified_oldest_pe...](https://en.wikipedia.org/wiki/List_of_the_verified_oldest_people))
I get the impression that the top two (Jeanne Calment and Sarah Knauss) don't
fit, though I know that the case of Jeanne Calment is very well documented.

~~~
tathougies
It's not intuitively obvious at all, since each replication of our cells leads
to our chromosomes getting ever smaller until presumably it starts eating into
genes that do useful things. Unless it's intuitively obvious to you that you
could live without genetic material at all, it seems quite obvious that --
given current biological processes -- there is a limit, even if that limit is
longer than where we've gone before.

~~~
bloak
Even if it were the case that each replication made the chromosomes smaller
(personally I would guess that there is a non-zero probability of them not
getting smaller and even a non-zero probability of them getting larger thanks
to a mutation) that would still only imply a hard limit on the number of
replications. You would also need to find a hard limit for how long a cell can
survive without replicating. Good luck with that.

I content that there are no limits: however old you are, you have a non-zero
chance of surviving another picosecond. The product of a finite number of non-
zero real numbers is non-zero, therefore...

Some people may wish to retort that at some point these numbers become so
small that they are no different from zero in practice. Those people are
probably not mathematicians. They're not wrong, either, of course, but they're
not making a valid argument for there being a limit.

There's no limit for the number of successive heads you can get when tossing a
coin, either, though you won't in practice see more than a hundred if it's a
reasonably fair coin. If there's no limit in that simplified, mathematical
situation, does it make sense to hypothesise that "there is a limit" in the
case of highly complex biochemical processes?

This is all very philosophical. It doesn't help us to estimate the chances of
a given person who is alive and 115 years old today (there seem to be about
five of them) one day breaking Jeanne Calment's record of 122. Are any
bookmakers taking bets?

~~~
Declanomous
>Even if it were the case that each replication made the chromosomes smaller
(personally I would guess that there is a non-zero probability of them not
getting smaller and even a non-zero probability of them getting larger thanks
to a mutation) that would still only imply a hard limit on the number of
replications.

The fact that chromosomes get shorter during DNA replication is a scientific
fact. Chromosomes have padding at the end called telomeres that provide a
buffer from the 'useful' DNA. There is an enzyme that can lengthen telomeres,
and its of great interest to scientists interested in extending human life.

There is almost no chance that mutations:

a) regularly occur in such a way that makes the chromosomal DNA longer,
especially in a way that offsets the base pairs lost during every
transcription.

and b) occur in the telomere area of the genetic code, after all the useful
bits of DNA.

If mutations did occur at a rate that would counteract the shortening of the
telomeres, the rest of your genome would be mutating so quickly you would
almost certainly die rather quickly.

There are a whole host of other reasons why what you wrote is nonsense, and I
don't have the time or the space to address them all. There is literally no
fact to what you have written. It is clear you don't have even a rudimentary
understand the biology of genetics. An understanding of math doesn't preclude
the need for understanding the actual mechanism of how things work.

The following articles are a useful primer to understanding the flaws in your
reasoning:

Okazaki Fragments:
[https://en.wikipedia.org/wiki/Okazaki_fragments](https://en.wikipedia.org/wiki/Okazaki_fragments)

Telomeres:
[https://en.wikipedia.org/wiki/Telomere](https://en.wikipedia.org/wiki/Telomere)

Telomerase:
[https://en.wikipedia.org/wiki/Telomerase](https://en.wikipedia.org/wiki/Telomerase)

DNA Polymerase:
[https://en.wikipedia.org/wiki/DNA_polymerase](https://en.wikipedia.org/wiki/DNA_polymerase)

DNA Replication:
[https://en.wikipedia.org/wiki/DNA_replication](https://en.wikipedia.org/wiki/DNA_replication)

~~~
bloak
That's all very interesting, but...

> almost no chance

That's my point, really. It might not be a terribly interesting point, but
you're conceding it, not refuting it.

Does genetics actually provide a useful estimate of the probability of someone
reaching the age of 123 years? I mean: something a bookmaker could use? Is
there any evidence that telomeres are practically relevant to the longevity of
humans in particular, as opposed to organisms in general, some of which live
very much longer than humans?

I humbly suggest that you turn down the pomposity a tiny bit. Read what you
wrote there:

> There are a whole host of other reasons why what you wrote is nonsense, and
> I don't have the time or the space to address them all.

What kind of impression do you think you're making?

~~~
Declanomous
I majored in Biology, with a focus in genetics and computer science because I
wanted to go into bioinformatics. I could literally write 30 pages about why
what you wrote is incorrect, and it would take several orders of magnitude
more time than it took you to write out your hypothesis.

I provided resources for you to educate yourself. If you believe that it isn't
a good use of your time, that's exactly how I feel about addressing the points
you made beyond broadly saying 'this won't work, here are resources that
address this on a level which you can understand.'

In this case 'almost no chance' is somewhat analogous to shuffling a deck of
cards and finding them in order by suit and value, and then shuffling them
again and finding them in _reverse_ order by suit and value, and repeating
that feat 10 times over.

The length of a human's telomeres when they are born is about 11k base pairs.
Chromosome 21 is the shortest chromosome, and has 46.7 _million_ base pairs.
That means with random chance a mutation is 4200 times more likely to occur in
the coding region of the chromosome than in the telomere.

Due to the way DNA Polymerase works, you will lose 20 base pairs of DNA on
every replication. Ignoring everything about rate of mutations and the
likelihood of insertion mutation, this means your chance of lengthening your
chromosome through mutations is (1/4200)^20, or 1 in 2.6x10^72.

The odds of shuffling a deck of cards and having it come out in suit and value
order is somewhere around 1x10^68.

That's using a best-case scenario as an example. Chromosome 1 has more than 5
times as many base pairs as chromosome 21, and you'd literally need to have
this happen on every single chromosome every single time you had cell
division.

~~~
Declanomous
A quick follow-up to this point. The exome, or coding region of the DNA is
approximately 1% of the genome, so arguably the chances of a mutation randomly
occurring in a coding region are 1/100 as probable as I suggested here.

There are a few caveats:

1) The non-coding region appears to be less useless than previously assumed.
There are still 'highly preserved' areas in non-coding regions. If a section
of the genome is highly preserved, it means that a mutation in that region
probably results in death/non-viability of the organism.

2) We know the rate of mutation of the genome. If random mutations were really
adding enough base pairs in the telomere region to lengthen it, the genome
would be growing at an incredible rate.

There are a lot of reasons why it's also implausible, but they have to do with
the amount of energy in a bond, etc. and other biochemistry stuff that I'm not
qualified to comment on.

------
nabla9
If I understand this correctly,

In the terms of probability aging distribution becomes memoryless for very old
people. This would mean that the remaining lifespan for really old people
would follow exponential distribution. Just like with radioactive decay, you
could determine their half life. The half life could be as short as one year.

>At that point, the researchers say, the odds of someone dying from one
birthday to the next are roughly 50:50

~~~
fjsolwmv
This could also be a subtle variation of the classic fallacy of confusing
exponential functions with sigmoids

------
reasonattlm
This really has nothing to do with limits to longevity in any practical sense.
That's just the publicity machine at work, the first line in mangling and
misrepresenting the relevance of research. This paper is to do with a long-
running debate over whether or not mortality risk reaches a high, flat plateau
in extreme old age. The difference between limit and high flat plateau is
academic for those involved. The outcome is much the same.

It does in flies, and there is very clear evidence for that. The evidence in
humans to date is very sparse, and where people have done good work on the
numbers, they have not seen signs of a plateau. So in that sense, that people
have found a larger data set that shows it, that is fuel for the fire.

No-one has the slightest idea as to how you can balance the fundamentals of
reliability theory with a late life mortality plateau. If damage is
accumulating, and no-one really believes it stops accumulating, then your risk
of mortality should keep on going up. What sort of mechanisms in a highly
damaged biology could buffer that underlying reality? And why in very late
life versus other times?

None of this, of course, has anything to do with efforts to treat aging or
extend human life. It is an academic debate that will likely fade out before
answers are found, made irrelevant by the advent of ways to treat aging and
its causes. Methods of extending life will work by putting off or repairing
the very damaged state. There will likely never be a large multiple of the
present count of exceptionally physiologically aged individuals. Rejuvenation
therapies are just around the corner.

------
sixdimensional
I wonder if there is something like the study I heard of once that said, if an
electronic or mechanical device lasts at least X years, it will almost always
last X + Y years where Y is a much longer period of time. I heard that related
to design, manufacturing process and material selection.

If it's true for things, it makes sense it might be true for humans.

~~~
elihu
It depends on the device, but there's also the phenomenon where failures go up
after a certain amount of time just because parts wear out.

[https://en.wikipedia.org/wiki/Bathtub_curve](https://en.wikipedia.org/wiki/Bathtub_curve)

------
mrfusion
If this is true shouldn’t we see the maximum lifespan increasing as population
has doubled several times?

~~~
olavk
Yes, but not much. Since mortality is about 50% for people over 100 (according
to the article), doubling the population of humans should only see an increase
of one year.

------
davesque
I'm sorry to say it, but I always feel incredibly cynical about longevity
tech. If we had a treatment that could extend people's lives indefinitely,
what would that do? It would essentially put a price tag on life in a more
direct way than we've seen before. It's hard to imagine that the powers that
be would want everyone to have fair access to it.

Obviously, this kind of treatment wouldn't at first be widely available even
if it worked. So how do we decide who gets it?

~~~
vagab0nd
May I ask, why you don't feel the same way for any other medical research that
saves lives? What's so different about curing aging?

~~~
davesque
Why do you assume I don't feel the same way about the things you mention?

In general, I think the economic incentives for medical tech are fucked up.

~~~
vagab0nd
Well, you mentioned you "feel incredibly cynical about longevity tech", which
seems to suggest that you feel differently on this particular type of research
compared to others.

------
qwerty456127
Who wants to live long without staying young? I'd rather choose to die in my
40-es if I would get 25-yr-old body until the end of the life in exchange.
Body/health (skin, brain, immune system, muscles etc.) anti-aging is the thing
we need first, not longevity/immortality.

~~~
grepthisab
Out of curiosity, how old are you now?

~~~
qwerty456127
I'm in my early 30-ies. I'm alright generally (I also look rather young and
the doctor says my health is great) but I already feel loss of vitality,
stamina, flexibility and regeneration. I felt like an invincible superhuman
when I was 24 and now, despite maintaining fairly healthy lifestyle, my knee
and back hurt occasionally, I can't f-ck without making a pause every couple
of minutes (used to do it for hours contiguously and vigorously until 28), I
have to eat healthy to maintain satisfyingly low weight (no wildly bad diet
could cause a fluctuation in my weight until 24) etc. I also feel very
satisfied by the life I have lived and occasionally think I wouldn't mind to
die happily at any time the G-d would decide my time on Earth to end (yet I
absolutely do mind to live long enough to get Alzheimer's, cancer etc, I don't
fear death yet I do fear senility). I have started to work-out vigorously to
revitalize and develop my body and mind recently so perhaps everything is
going to change as I achieve the results yet I doubt things like my knee are
going to regenerate (this has been scientifically proven impossible in 2017 or
2016 as far as I can remember although I can't find a link to the paper now).
It seems it's a fact that 30+-yr-old bodies are generally more fragile and
less powerful than 20-yr-old ones.

------
SketchySeaBeast
It's a 50/50 change once 105, and given that the odds of 32 coin tosses all
coming up heads is 1 in 4,294,967,296 does that mean there's a 137 year old
person running around somewhere?

~~~
vinceguidry
Methuselah lived 969 years, so there's that data point. _ducks_

~~~
SketchySeaBeast
I'm only in my early 30's and I am already considering myself 35, at 969 you'd
think you'd round up to an even thousand. I'll only believe that exact time if
someone counts the rings.

~~~
vinceguidry
The Hebrews took from the Egyptians a great love of numbers and numerology.
969 probably rolled off the tongue really well in their language. It was all
originally passed orally in verse.

~~~
stan_rogers
I once took up the Ussher chronology thing, wading through the begats, just to
see if there was any sort of basis on which a person could legitimately
convince themselves they _were_ doing a proper chronology. Turns out that 969
means ol' Meth drowned in the Flood his grandson was known for - or at least
kicked off in the few months preceding it. I'm thinking "drowned in the Flood"
is something you're supposed to carry away from the tale, in much the same way
as he's listed as somebody's son and somebody's father, without any
accomplishments worth mentioning, nor any notable piety. There's probably
another part of the tale, now lost, that folks were originally supposed to
know.

------
unit91
Given that theory, we never see people over about 120 because...?

~~~
meiraleal
Some speculations:

1\. there are few, as the world has 7billion++ people today and 120 years ago
it was around 1 billion. You certainly are not going to meet them.

2\. Someone that is still sane past 100 years will not care about bragging his
age to us younglings.

3\. Finally, we don't ask these people their age. And when we do, we don't
believe the answer.

There are some histories of people with more than a hundred year. Li Ching
Yuen[1] was a Chinese herbalist that lived more than 250 years.

1\. [https://en.wikipedia.org/wiki/Li_Ching-
Yuen](https://en.wikipedia.org/wiki/Li_Ching-Yuen)

~~~
tomrod
Any time I see these kinds of claims, I like to take a step back and think
through a few points. Does it happen frequently? How much evidence would I
need to shift my prior from unlikely to likely? Is someone trying to sell me
something, literally or metaphorically?

This skepticism is borne from living a life of being gaslighted and conned in
a high-demand religion, and breaking away. I don't doubt there are
occasionally a few long-tail events that skepticism causes one to miss its
reality, but as far as seeking mysticism or a hidden reality (hidden by
whatever underlying power, be it gods or billionaires, pick your poison) I
find life much less stressful and more fulfilling with a healthy dose of
skepticism.

~~~
JTbane
>This skepticism is borne from living a life of being gaslighted and conned in
a high-demand religion, and breaking away.

That kind of statement begs for a story.

~~~
tomrod
I don't want to threadjack, just will point out many of these stories can be
found in Reddit's EX communities: exjw, exmuslim, exmormon, and similar. The
evolution of these communities into support groups over time has been
fascinating.

------
ilaksh
I always link to [http://www.sens.org](http://www.sens.org) when aging comes
up because their approach makes the most sense to me.

~~~
jz_
I've donated 300 USD to them this month.

------
yazaddaruvala
I'm so excited! Every time I read an article about longevity, its like
Christmas morning.

Everlasting youth is going to be humanity's greatest accomplishment, and its
biggest weakness.

~~~
gldalmaso
It always comes to mind how many fictional immortal characters and creatures
just basically choose to go into an eternal slumber. There seems to be a de
facto consensus that it is actually pretty boring stuff.

~~~
tzs
Perhaps it is a way to deal with limitations of their brains. They usually
have finite brains, which presumably have a limit on how much information they
can store and organize and process.

Suppose you are an immortal working on some long term goal, some plan that
will take a few hundred years to complete. It is a complicated plan and you
will need to keep it all in your mind, along with its history as it
progresses, in order to guide it to success.

If you try to lead an active life throughout all this, perhaps your brain will
acquire too much irrelevant information, interfering with your ability to
carry out your plan.

So you sleep for decades at a time, just waking up long enough to check on the
plan, learn about changes to the world since your lest check, and make
adjustments. Then back to sleep.

