
Why We Age - Mitchhhs
http://mitchkirby.com/2015/05/19/why-we-age/
======
reasonattlm
You might also see the great short introduction to the conservative scientific
view on aging here:

[http://senescence.info/aging_theories.html](http://senescence.info/aging_theories.html)

You'll also find a good introduction to the modern "aging is damage" viewpoint
in the SENS distillation of consensus positions from various per-disease
research fields:

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

That is one synthesis of which damage is primary and important. Another is the
Hallmarks of Aging:

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/)

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the_kingsley
It would be great to stay young.

I'm happy to report that scientists have been seriously testing if stuff
actually works for over a century (Slonaker, 1912).

They typically try an intervention, like diet or exercise, on lab animals, and
then see how long they live.

For what it's worth, I maintain the world's biggest spread sheet of these life
span experiments.

It summarizes over 14,000.

One column is the intervention (diet, exercise, etc..) another is the change
in lifespan (+10%, -2%, etc...) another is the species (human, mice, etc...)
and so on.

It's interesting to see what works.

More info is at

[http://morse.kiwi.nz/kingsley/doku.php?id=science:start](http://morse.kiwi.nz/kingsley/doku.php?id=science:start)

~~~
gavazzy
You want $1,000,000 to get the report of life span experiments?

~~~
themartorana
Also he has stripped electromagnetic waves to just get magnetic waves and he
doesn't know about man-made climate change because of correlations.

~~~
gavazzy
Whoa, he should submit his results to Nature!

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evo_9
Interesting and thorough article, very good read.

I've posted about some of the interesting stuff going on regarding stem cells,
particularly around hockey legend Gordie Howe's rather miraculous recover from
a stroke earlier this year. I'm really not sure why this isn't getting more
news nationally, or even why on HN it isn't getting any traction/discussion:

[http://www.freep.com/story/sports/nhl/red-
wings/2015/05/18/g...](http://www.freep.com/story/sports/nhl/red-
wings/2015/05/18/gordie-howe-stem-cells-detroit/27536175/)

~~~
mrfusion
[https://news.ycombinator.com/item?id=9566335](https://news.ycombinator.com/item?id=9566335)

~~~
evo_9
That's my original post yesterday for this story. No discussion or
interest/upvote.

So is it simply that the average HN'er is around 28 years old and just doesn't
care about aging or stem cell research that is mostly aimed at fixing 'old
people'? Is everyone just assuming this stuff will get sorted out in the next
20 years by time the average HN'er actually needs to worry about it?

Or is it because the stem cell medical centers that provided Mr. Howe with the
treatments are outside the US? Aka, not invented here so must be BS?

It's puzzling, I mean we all have parents that are aging and having gone
through watching a parent lose a lot of their capabilities from a stroke last
year (and eventually dying from the strokes fallout a few months later), all I
can say is this stuff can become front and center to your personal interest
very rapidly when it hits home.

~~~
bootload
_" That's my original post yesterday for this story. No discussion or
interest/upvote."_

The surface area of HN is so broad, the number of readers interested in pretty
low. This is a observable problem. I often see lots of votes and zero
responses for interesting posts.

Interesting enough to click, glance over, but not enough to think about and
comment.

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farresito
The more I read about aging, the more interested I become about the subject,
especially after Google created Calico and after watching some talks by Aubrey
de Grey.

Reversing aging seems like such a science fiction thing, but then you take a
look at how things were 50 years ago and how things are right now and you
realize that a lot of the things that seem impossible right now might very
well be possible in 20, 30 or 50 years.

~~~
reasonattlm
We are living in the midst of the early phases of a biotechnology revolution
every bit as profound and transformative as the computing revolution from the
1970s on. It is less apparent than it might be to the average person in the
street because (a) next to no-one really spends much time thinking about
medical research unless they have to, which is a whole massive issue with our
society in and of itself, (b) regulatory burdens on medical technology ensures
that the clinic is 10-20 years behind the bounds of the possible in the labs.
Medical tourism does its part to help keep that delay lower than it might, but
it's still a huge burden, and a huge cost in life - especially now that the
upward curve of progress is potentially so steep.

The potential to be able to treat aging and begin to bring it under medical
control within the next 20 years - IF the right research fields begin to
dominate the mainstream, IF the funding arises, IF the public wakes up and
regards aging research in the same was as they regard cancer research - is
very real. That is why people like me spend time and effort to bang the drum,
conduct grassroots fundraisers, and support progress in SENS-like rejuvenation
research focused on repair of the cellular and tissue damage thought to cause
aging. For example, clearance of senescent cells, an approach which has just
now reached the point of credible demonstrations in normal mice, but needs
much more support to make it into the mainstream. Is Calico funding this? No,
not yet, and they won't until it gets more support:

[http://www.scripps.edu/news/press/2015/20150309agingcell.htm...](http://www.scripps.edu/news/press/2015/20150309agingcell.html)

Advocates and the research community are making progress, great progress when
you look at 2015 in comparison to the state of things in 2005, but we need
more people to take the step, become philanthropists, and materially support
this and other early-stage research with the aim of bringing medicine under
medical control. That support really does make a difference.

~~~
farresito
Thank you for your answer and for supporting this research! I know it's very
hard to do, especially with things in such a young state, but do you think you
could provide any more information of where we might be in 10, 20 or 50 years?

~~~
reasonattlm
A toolkit for producing true rejuvenation in humans will require a range of
different therapies, each of which can repair or reverse one of the varied
root causes of degenerative aging. Research is underway for all of these
classes of therapy, but very slowly and with very little funding in some
cases. The funding situation spans the gamut from that of the stem cell
research community, where researchers are afloat in money and interest, to the
search for ways to break down advanced glycation endproducts (AGEs), which is
a funding desert by comparison, little known or appreciated outside the small
scientific community that works in that field.

While bearing in mind that progress in projects with little funding is
unpredictable in comparison to that of well-funded projects, I think that we
can still take a stab at a likely order of arrival for various important
therapies needed to reverse aging. Thus an incomplete list follows, running
from the earliest to the latest arrival, with the caveat that it is based on
the present funding and publicity situation. If any one of the weakly funded
and unappreciated lines of research suddenly became popular and awash with
resources, it would probably move up in the ordering:

1) Destruction of Senescent Cells

Destroying specific cells without harming surrounding cells is a well-funded
line of research thanks to the cancer community, and the technology platforms
under development can be adapted to target any type of cell once it is
understood how to target its distinctive features.

The research community has already demonstrated benefits from senescent cell
destruction, and there are research groups working on this problem from a
number of angles. A method of targeting senescent cells for destruction was
recently published, and we can expect to see more diverse attempts at this in
the next few years. As soon as one of these can be shown to produce benefits
in mice that are similar to the early demonstrations, then senescent cell
clearance becomes a going concern: something to be lifted from the deadlocked
US regulatory process and hopefully developed quickly into a therapy in Asia,
accessed via medical tourism.

2) Selective Pruning and Support of the Immune System

One of the reasons for immune system decline is crowding out of useful immune
cells by memory immune cells that serve little useful purpose. Here, targeted
cell destruction can also produce benefits, and early technology
demonstrations support this view. Again, the vital component is the array of
mechanisms needed to target the various forms of immune cell that must be
pruned. I expect the same rising tide of technology and knowledge that enables
senescent cell targeting will lead to the arrival of immune cell targeting on
much the same schedule.

Culling the immune system will likely have to be supported with some form of
repopulation of cells. It is already possible to repopulate a patient's immune
system with immune cells cultivated from their own tissues, as demonstrated by
the limited number of full immune system reboots carried out to cure
autoimmune disorders. Alternatives to this process include some form of tissue
engineering to recreate the dynamic, youthful thymus as a source of immune
cells - or more adventurous processes such as cultivating thymic cells in a
patient's lymph nodes.

3) Mitochondrial Repair

Our mitochondria sabotage us. There's a flaw in their structure and operation
that causes a small but steadily increasing fraction of our cells to descend
into a malfunctioning state that is destructive to bodily tissues and systems.

There are any number of proposed methods for dealing with this component of
the aging process - either repairing or making it irrelevant - and a couple
are in that precarious state of being just a little more solidity and work
away from the point at which they could begin clinical development. The
diversity of potential approaches in increasing too. Practical methods are now
showing up for ways to put new mitochondria into cells, or target arbitrary
therapies to the interior or mitochondria. It all looks very promising.

Further, the study of mitochondria is very broad and energetic, and has a
strong presence in many areas of medicine and life science research. While few
groups in the field are currently engaged in work on mitochondrial repair,
there is an enormous reservoir of potential funding and workers awaiting any
method of repair shown to produce solid results.

~~~
mrfusion
Thanks for the detailed write-up. Very interesting reading!

I don't understand what you're saying about pruning the immune system. What is
that trying to fix? What goes wrong with the immune system as it ages?

~~~
reasonattlm
The immune system operates more or less as a limited capacity system. It has
low levels of replacement of immune cells in old age. For reasons that may
have to do with exposure to persistent herpesviruses there is an expansion of
memory cells and related types at the expense of the naive T cells needed to
deal with new threats.

So the quick and dirty solution to this, which has some support from animal
studies in the past few years, is to selectively kill off the undesirable
excess memory cells. Perhaps via one of the targeted cell killing technologies
developed in the cancer research community. This should free up capacity and
spur the generation of more naive T cells to replace the lost numbers. It
isn't a reality yet, but all the pieces are more or less in place. Someone
just needs to do it.

A similar thing was demonstrated for B cell destruction in mice (innate
immunity, not adaptive immunity): the bad cells were stripped out, and fresh
new cells were generated as a result, and the innate immune response improved.

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pseud0r
For anyone interested in why we age and what research needs to be done to cure
it, I'd recommend this article

[http://protein.bio.msu.ru/biokhimiya/contents/v78/pdf/bcm_10...](http://protein.bio.msu.ru/biokhimiya/contents/v78/pdf/bcm_1061.pdf)

The most interesting part is that a relatively simple medical procedure called
plasmapheresis or plasma exchange, might be used for rejuvenation. The process
would be to exchange the blood plasma of an old person with that of a young
person many times over a period of time.

The blood plasma contains signaling molecules and there is strong evidence
that some of them are used to synchronize the current age throughout the body,
perhaps to a master clock somewhere. This causes telomeres to be shortened,
DNA repair mechanisms to be turned off, stem cells to stop dividing etc. If
the clock could be reset with young plasma, the stem cells would be reset to a
young state and can start dividing again to regenerate tissue. Experiments on
rats suggests this is indeed happening and a number of academic labs and even
a startup called alkahest is now working on getting this tested in humans.

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markbnj
I find the life expectancy vs. heart rate graph very interesting. The human
point is the only one that lies well off the line of correlation, and it's
tempting to see the distance as a result of our technological achievements. In
other words, we're the only animal to have pushed ourselves to the right of
that line by being able to fix at least some of what goes wrong.

~~~
Qantourisc
There is another theory about this: older humans are not 100% useless, they
provide wisdom and skills to the younger people. As such communities with (not
a burden) elder people have an advantage. And this removes some of the
selection shadow.

~~~
kaybe
Humans are not the only species for which this is true though.

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shenanigoat
This article was very well presented, clear, and informative. Thank you. I
look forward to your next one(s).

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jostmey
I love this article! The author points out that as lifespan goes up the effect
of aging on fitness goes down. So provided that an organism lives long enough,
aging is not penalized by Natural Selection.

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ExpiredLink
> _If you think about it, nearly all things age. Your car. Wine. Cheese. The
> electronic device you’re reading this on._

Actually, no. Those things don't 'age' like you age.

BTW, trying to answer existentialist questions with biological theories is
futile.

~~~
Florin_Andrei
At the bottom, it's all an increase in entropy. That's my standard answer,
probably informed by my college studies (Physics, not CS).

The layers on top might be different, but at the very bottom of things, it's
always entropy "trying" to increase. That's why computers eventually break,
that's why living things age and die.

To counteract this tendency, you'd have to somehow prevent the entropic
increase within each system. Technically doable, but the devil is in the
details. Life itself fights entropy, the problem is that whatever anti-
entropic mechanisms it employs, they're not stable long-term, at least not for
pluricellular organisms as separate systems. The biosphere as a whole has
actually been remarkably resilient so far.

