
Human age limit claim sparks debate - othello
http://www.nature.com/news/human-age-limit-claim-sparks-debate-1.20750
======
zargon
Medicine hasn't even attempted to extend human lifespan. To date it has only
adressed causes of premature death. These conclusions have this baked-in as a
(quite probably unconscious) assumption. Medicine needs to grow beyond this
short-sightedness.

~~~
Iv
Also, medicine is only concerned about bringing people with problems back to
the "average normal" health state. What if I want to improve on the average?

~~~
toomuchtodo
[https://en.wikipedia.org/wiki/CRISPR#Cas9](https://en.wikipedia.org/wiki/CRISPR#Cas9)

~~~
Iv
Sorry, I fail to see the connection?

~~~
toomuchtodo
CRISPR allows for the in place editing of your genome, which is going to be
necessary to extend your life significantly or make you an above average
human.

------
bsder
The big issue is that mortality seems to not fit any of the normal statistical
distribution models. If it did, we would have a few stragglers at 150+ years
old. That never happens.

So, the question becomes: "What is inherent in the human body that causes
mortality to not be statistically distributed?" That's the _real_ argument.

~~~
samatman
We know of at least one such thing: telomeres.

Cells have a definite amount of time before they undergo mitosis, and
telomeres always shorten with each mitosis.

This puts at least one limit on longevity; there are likely to be others.
Evolution exerts little-to-no selection pressure for organisms to survive past
the caretaker period; in humans, that's grandparents at most.

~~~
nonbel
Not necessarily an issue:

"Approximately 7x10^15 mature cells are produced in a human lifetime and these
could be produced in 53 cell generations (2^53 = 9x10^15). In 60 cell
generations a total of 10^18 cells would be produced, enough for over 1000
years of human life. Thus it is possible that, even in extreme old age, the
mature cells of the body are fewer than 60 generations from the zygote."
[https://www.ncbi.nlm.nih.gov/pubmed/25459141](https://www.ncbi.nlm.nih.gov/pubmed/25459141)

It may be that rather than limiting lifespan, telomere length is a result of
other constraints on lifespan. There may be no point to making them longer.

~~~
Retric
This is not how the body operates, skin and gut cells reproduce far more often
than normal.

~~~
nonbel
According to the paper I linked to, as of 2014 that was a long-held
assumption, one that has lead to a number of "paradoxes" (ie, is in conflict
with observation). What evidence are you thinking of?

~~~
Retric
The most obvious is the response to heavy radiation poising or chemotherapy
show a range of responses consistent with various rates of cell division.

~~~
nonbel
I think the confusion is due to you thinking of the total number of cell
divisions, while I am thinking of the number of divisions separating a given
cell from the zygote.

This lead me to misunderstand the relationship you were claiming between "This
is not how the body operates" and "skin and gut cells reproduce far more often
than normal".

~~~
Retric
I think we where talking past each other.

Bone marrow for example needs to continuously create Blood cells with a short
lifespan. (Adult humans have roughly 20–30 × 1012 (20–30 trillion) red blood
cells at any given time, comprising approximately 70% of the total human body
cell number.)
[https://en.m.wikipedia.org/wiki/Red_blood_cell](https://en.m.wikipedia.org/wiki/Red_blood_cell)

Thus your bone marrow must create new cells at a much faster rate than
average, making the average a meaningless number.

Now you might think you could design bone marrow to minimize the number of
generations nessisary to produce that blood, but it does not operate with such
efficiency. In large part because fewer cell generations does not mean fewer
mutations.

~~~
nonbel
If you check the paper, you will see it describes a scheme that minimizes the
number of generations while maintaining the observed rate of cell division.
The average rate of division across tissues isn't really at issue here,
tissues that require fewer cells will just have a shallow hierarchy.

>"it does not operate with such efficiency"

Most likely it does not operate at max efficiency. However, since most
mutations seem to occur during mitosis, it would make a lot of sense for
natural selection to optimize (number of divisions)/(generations from zygote).

~~~
Retric
First, it's not the number of generations that are the direct risk. A cell
that does nothing will still mutate over time. It's large numbers cells that
share a few risky mutations that are the problem.

If you have a 1,000 cells that can do 30 generations without hitting
programmed cell death then a single mutation that kicks that off can form a
large mass without tripping your body's alarms which also share that mutation.
Even if they end up as a non cancerous mass that large mass is very likely to
cause problems.

On the other hand if you have 1 billion cells that can each do 10 generations
and they all formed young you still get the same 1 trillion cell potential,
but don't risk that single mutation as those 1 Billion cells showed up at a
young age. Further, when some of those 1 million cells start growing
uncontrollably they only grow to 1,000 cells before hitting programmed cell
death which is a lower cancer risk.

Now sure, the body can play around with these numbers to form a crazy number
of skin, gut, and blood cells from some relatively small cell pools. But, it's
already playing those games while minimizing cancer risk. So, we don't have
some pool of 'young' cells to solve problems late in life because it's to
dangerous to keep them around.

PS: People often thing of their body's as kind of a tub of undifferentiated
mass. But, cells a body structures are optimized for a huge number of problems
that only become obvious with deep investigation.

~~~
nonbel
>"First, it's not the number of generations that are the direct risk. A cell
that does nothing will still mutate over time. It's large numbers cells that
share a few risky mutations that are the problem."

If this is correct, I think you would likely be right. Do you have a
reference?

------
reasonattlm
It serves as a reminder that the research community actually knows very little
about the demographics of aging at very advanced age. The data is so sparse
past age 110 that the statistics of mortality, very reliable in earlier old
age, rapidly turn into a sludge of uncertainty. It is possible at this point
in time to argue either side of the position that there is or is not a limit
to longevity under present circumstances, though most of us probably think
that one or the other side is weak. On the one hand we can theorize that
maximum human life span is increasing, in a way analogous to the fact that
life expectancy at 60 is inching upward at a year every decade, but more
slowly, and we might suggest the data for extreme old age is so bad that the
ongoing change can't be identified. On the other hand we can instead theorize
that there is some limiting process that hasn't changed at all over the course
of recent human history, is not impacted meaningfully by modern medicine,
plays a very large role in supercentenarians in comparison to younger old
people, and renders mortality rates so very high at the extremes of human life
spans as to form a limit.

This is actually a point worth making twice: when limits to lifespan are
discussed, we're not talking about actual limits per se, but effective limits.
A very large mortality rate, possibly coupled with rapid growth in mortality
rate over time, looks a lot like a hard barrier to further progress in
practice, but there is still the chance that someone could beat the odds.
Where the data for supercentenarians is good enough to fill in tentative
mortality rates with large error bars, up to age 115, that rate is around 50%
annually [1]. The mortality rate may increase greatly after that point, and
that would be entirely expected given the absence of more than the one
certified example making it past 120, but it is very unclear from the limited
data. Mortality rates reflect actual physical processes, the accumulation of
forms of cell and tissue damage that cause the suffering, death, and disease
of old age. The damage is the same, but the proximate causes of death for
supercentenarians are quite differently distributed from those of younger old
people, prior to a century of age. The majority appear to be killed by
transthyretin amyloidosis [2] that clogs up the cardiovascular system, and
that is becoming known to play a much lesser - but still significant role - in
heart disease in earlier old age. Could this form of amyloidosis be the
candidate for a process that is not all that affected by the past century of
changes in medicine and lifestyle, and that becomes much more important in
extreme old age than early old age? Possibly. The only way to know for sure is
to build ways to clear this form of amyloid [3] and see what happens.

The natural state of aging is a function of damage and how medicine addresses
that damage - which is poorly and next to not at all at the present time.
Almost all medicine for age-related conditions fails to address their root
causes, the cell and tissue damage of aging [4], and takes the form of
patching over that damage in some way or coaxing biological machinery to cope
slightly better with running in a damaged environment. Predictably it is
expensive and only marginally effective in comparison to true repair. As above
in the comments on amyloidosis, find a way to repair that problem and life
span will increase, as the machinery of biology will be less damaged and less
worn down into high rates of failure. That is the point to take away from this
discussion. It has to be said that the lead of the study, Jan Vijg, comes
across as very pessimistic on aging in his comments here when considered in
comparison to past remarks and collaborations with SENS folk [5] that I've
seen from him. That is the case even granting that he is in the camp of
researchers who believe there is no alternative to a very slow and expensive
reengineering of human metabolism in order make incremental gains in life span
and slowing of the aging process.

[1]:
[http://dx.doi.org/10.1007/978-3-642-11520-2](http://dx.doi.org/10.1007/978-3-642-11520-2)

[2]: [http://dailybruin.com/2010/03/04/autopsy-115-year-old-
aids-r...](http://dailybruin.com/2010/03/04/autopsy-115-year-old-aids-
research/)

[3]: [http://www.uclb.com/news-and-events/news-post/potential-
new-...](http://www.uclb.com/news-and-events/news-post/potential-new-approach-
to-the-treatment-of-systemic-amyloidosis)

[4]: [http://www.sens.org/research/introduction-to-sens-
research](http://www.sens.org/research/introduction-to-sens-research)

[5]:
[http://dx.doi.org/10.1159/000357670](http://dx.doi.org/10.1159/000357670)

~~~
madebysquares
One of the best most thorough comments I've ever seen. Thank you for citing
all those sources.

------
tracker1
It looks like not many people died in the 70's, I think we need to bring back
disco, bell bottoms and pot smoking!

Seriously though... antibiotics and widely available and distributed
vaccinations have done more for human longevity on average than anything else.

~~~
oldmanjay
Disco-descendants and weed are perennially popular and I'm sure bell bottoms
will come back through the endless cycle of fashion repetition. Devise some
experiments now to test your hypothesis.

------
vorotato
I read the title and thought they were talking about a legal limit. Sir you
are 15 years older than the legal limit.

------
astaroth360
Yeah, except they don't include any sort of scientific advance. Who cares
about the natural age limit? We're mankind, the first species to be able to
guide our own evolution. Basically this article means nothing significant.

