
Clinical trial finds blood-plasma infusions for Alzheimer’s safe, promising - monort
https://med.stanford.edu/news/all-news/2017/11/clinical-trial-finds-blood-plasma-infusions-for-alzheimers-safe.html
======
reasonattlm
Safe, yes, but I think "promising" is more aimed at the investors than a
reflection of reality. Both Alkahest and Ambrosia's results are essentially
ambiguous, which reflects the equally ambiguous animal data for plasma
transfusion.

This isn't going to stop other people from trying analogous things.

The Conboys are trying apheresis to strip out harmful factors from old blood (
[https://www.leafscience.org/conboy-
interview/](https://www.leafscience.org/conboy-interview/) ), which seems to
me unlikely to move the needle either, and other groups are trying to identify
and deliver signals from young blood.

What all of these things have in common is that they are failing to address
root causes. Why does signaling change in old blood and tissues? Because the
cells that generate that signaling are either damaged or reacting to damage.
Trying to force the signaling to be more youthful has very definite limits -
it might compensate a little for one consequence of the damage, but that
damage is still there, still producing all of the other problems that it
causes. The "change the signaling" approach requires the research community to
map every single one of potentially hundreds or thousands of individual
changes, then understand which are relevant, and then run individual projects
for each one. It just won't happen - look at the cancer research community for
a guide as to how slowly that sort of scenario progresses.

The plausible outer limits of signaling adjustment are probably indicated by
the effects of first generation stem cell therapies, which largely work
through the signals introduced by the transplanted cells. Assume that
something somewhat better than that can be achieved: meaning temporarily
improved regeneration, less increased cancer risk than was originally
suspected, but not much of an impact on aging and age-related disease, when
considered in the context of the bigger picture of what is possible.

(What is possible if people would just stop tinkering with downstream
consequences and start repairing the root cause damage. At least the flurry of
interest in senolytics is a start in that direction, and should hopefully
prove the point by being so very much better and more cost-effective than just
about everything else on the market when it comes to treating age-related
conditions).

~~~
danieltillett
All of these approaches are going to run into the reason why ageing is
happening in the first place - to prevent cancer. Ageing is one of the
original anti-oncogenic systems and anything that messes with the rate of
aging without doing something about cancer is doomed to failure.

Interesting there are some human mutations that slow down the ageing rate [1].
These all cause an increased cancer rate, but if you manage to make it to old
age you are physiologically much younger (20-30 years in the case of the
Brazilian p53 mutation).

1\.
[https://www.ncbi.nlm.nih.gov/pubmed/27663983](https://www.ncbi.nlm.nih.gov/pubmed/27663983)

~~~
reasonattlm
Which is why the SENS portfolio includes a universal cure for cancer.

This is not as hard as people have been made to think it is. The present
mainstream approach of the past few decades is just not a good one. It is
picking strategies that are very expensive to implement, and that attack
vulnerabilities that are peculiar to tiny subtypes of cancer. There are
hundreds of subtypes of cancer, most of which are cheerfully capable of
evolving their way around many of the existing attacks on their biochemical
vulnerabilities. There are only so many scientists, only so much funding. If
it takes twenty man-years to produce a therapy to tackle transient
vulnerability A in subtype 1 of 1000, we'll never see the end of it. Yet this
is largely what is happening.

What should be happening instead is the whole-hearted pursuit of
vulnerabilities that are common to many, many types of cancer, or all cancers
for preference.

There is one very good one, which is that cancers must lengthen their
telomeres, and there are only two ways for that to happen, neither of which
should really be operating in somatic cells. So block telomerase, block ALT,
and get that hooked up to some kind of cancer-cell-targeting-mechanism of the
sort that has been under development for the past decade, and that will work
to kill any cancer. A number of high profile groups are working on telomerase
sabotage ( [https://www.eurekalert.org/pub_releases/2015-01/usmc-
rtt1231...](https://www.eurekalert.org/pub_releases/2015-01/usmc-
rtt123114.php) ), and the SENS Research Foundation has been funding the
necessary research to address ALT (
[http://www.sens.org/research/introduction-to-sens-
research/c...](http://www.sens.org/research/introduction-to-sens-
research/cancerous-cells) ), still at comparatively early stages.

There are other, prospective targets. The comparative biology crowd is reverse
engineering naked mole rats to figure out what it is that makes them next to
immune to cancer. There are a few leads there; p21, ARF, hyaluronan,
alpha2-macroglobulin, etc. Another recent discovery relates to re-engaging the
limitation on processing nutrients; apparently all cells have a food limiter,
and all cancers abuse that limiter in order to enable rampant replication. Re-
enable the limiter and cancers wither: [https://www.salk.edu/news-
release/salk-scientists-curb-growt...](https://www.salk.edu/news-release/salk-
scientists-curb-growth-cancer-cells-blocking-access-key-nutrients/)

So there is no shortage of possibilities for people who want to kill all
cancer. There is no excuse for continuing the wasteful business as usual of
the past decades. This is an age of revolutionary progress in biotechnology -
we should act like it and aim high.

~~~
nonbel
>"there is no shortage of possibilities for people who want to kill all
cancer."

Your posts in this thread make me think you have a different view of what is
going on regarding aging and cancer than I do...

As mentioned below, it seems that after each division more and more "genetic
errors and other junk" accumulate in tissue stem cells. After a certain number
of these divisions the stem cell needs to stop replenishing the tissue because
the risk of generating a cancer cell is too high. Thus the turnover of
terminal cells must slow and eventually stop as each tissue stem cell becomes
"exhausted".

So the options upon exhaustion (of safe divisions) of the stem cells are
either:

1) Continue replenishing the tissue at a high risk of cancer. Even the non-
tumorgenic new terminal cells are also becoming less and less functional due
to the accumulated erros/junk.

\- high cancer risk, slow organ failure

2) Stop replenishing the tissue and let whatever cells are there survive as
long as possible (these are the senescent cells).

\- low cancer risk, slow/intermediate rate organ failure

3) Stop replenishing the tissue _and_ remove the senescent cells, replacing
the space with connective tissue. In this case the tissue will become less and
less functional eventually leading to organ failure.

\- low cancer risk, fast organ failure

All of your ideas proposed here seem to be #1 or #3. Nature's solution is #2,
and probably for good reason.

Also, obviously the ultimate solution needs to be either reducing the number
of cell divisions or the rate of junk/error accumulation per division. This
all seems to follow very easily from the premise that errors/junk accumulate
after each division, so I would be interested to know what you are reading
that makes you think it is incorrect.

~~~
danieltillett
The other solution is as suggested which is increase the robustness of the
anti-oncogene systems. This way the stem cells will still accumulate mutations
(hard to solve this problem), but they won’t progress to cancer.

This approach is how evolution has solved the problem of cancer in large
animals with long lifespans.

~~~
nonbel
What do you mean by "anti-oncogene systems? That makes me think of stuff like
this:
[https://en.wikipedia.org/wiki/Tumor_suppressor_gene#Function...](https://en.wikipedia.org/wiki/Tumor_suppressor_gene#Functions)

Those functions are pretty much the same as what I mentioned above (adhesion
isn't included in my list):

"obviously the ultimate solution needs to be either reducing the number of
cell divisions or the rate of junk/error accumulation per division"

~~~
danieltillett
Tumor suppressor is a synonym for anti-oncogene. The systems present in each
species is not the same and the large long lived animals of more and better
systems. Unfortunately, we don't know too much about them.

~~~
nonbel
That is called Peto's paradox:
[https://en.wikipedia.org/wiki/Peto%27s_paradox](https://en.wikipedia.org/wiki/Peto%27s_paradox).
Afaik the idea that larger animals have more robust tumor suppression systems
is an assumption required due to a possibly incorrect understanding of the
stem cell division scheme:
[https://www.ncbi.nlm.nih.gov/pubmed/25459141](https://www.ncbi.nlm.nih.gov/pubmed/25459141)

If you look close enough at this topic you will realize that we don't have
good data on how many divisions are actually happening in each tissue. Our
understanding is very rudimentary so it is extremely dangerous to take
anything as fact on this topic. As a science, cancer research is not even yet
at the point of astronomy when people began estimating the number of stars...

It is in a pre-astrology stage where all sorts of wild speculations and fads
reign supreme.

EDIT:

Note that in the Morris 2014 paper I linked he calls Peto's paradox the "man-
mouse paradox" and uses 'Peto's paradox' to mean something else.

~~~
danieltillett
We actually know that elephants have extra systems for controlling cancer and
we haven't really looked carefully [1]. We have also learned a little about
these systems in bowhead whales [2].

I think we are a bit further along with understanding cancer (we haven't found
a major oncogene in a while), but I do agree we still have a way to go,
especially on the treatment/prevention front.

1\. [https://www.nature.com/news/how-elephants-avoid-
cancer-1.185...](https://www.nature.com/news/how-elephants-avoid-
cancer-1.18534)

2\.
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536333/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536333/)

~~~
nonbel
This is still wild speculation. "Elephants live a long time and have multiple
copies of p53" (these retrotransposed copies so they are under different
promoters, missing introns, etc ...) does not equate to what you said. Look at
all the functions for p53 on the right of this page:
[https://en.wikipedia.org/wiki/TP53](https://en.wikipedia.org/wiki/TP53)

It is not difficult at all to look at a genome and find some pattern that you
can weave a plausible story around.

Also, here are the conclusions of your two papers:

> _" To our knowledge, this study offers the first supporting evidence based
> on empirical data that larger animals with longer life spans may develop
> less cancer, especially elephants.

[...]

Compared with other mammalian species, elephants appeared to have a lower-
than-expected rate of cancer, potentially related to multiple copies of
TP53."_

> _" The genetic and molecular mechanisms by which longevity evolves remain
> largely unexplained"_

Now consider how simplistic the idea behind these studies is:
"Elephants/whales live a long time and are rarely observed to get cancer
relative to humans, we should look into why". Investigation of the most basic
aspects of the problem has only begun a few years ago...

------
obeone
When these findings came out in November, SciMag felt the results were less
promising. [https://www.sciencemag.org/news/2017/11/blood-young-
people-d...](https://www.sciencemag.org/news/2017/11/blood-young-people-does-
little-reverse-alzheimer-s-first-test)

