Clinical trial finds blood-plasma infusions for Alzheimer’s safe, promising
med.stanford.edu
med.stanford.edu
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/ ), 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).
And what about targeting the level of cytokines? The immune system is sometimes running on free wheels (aging, autoimmune, etc)
Let the body regulates itself.
Senescent cells are one of the root cause of aging. Signaling changes in old blood are downstream of the root causes of aging - secondary and later consequences.
Senescent cells are created by the operation of normal processes of healthy, youthful metabolism, and if their numbers can be periodically culled, then their contribution to aging will be removed.
If your car is flagging, you repair the engine by replacing a damaged part, not by pressing the accelerator harder. Removing senescent cells is replacing a damaged part. Overriding signaling changes is pressing harder on the accelerator, while ignoring the damage.
Removing != replacing. What are you replacing the senescent cells with?
Replication from where though? The tissue stem cell that has already divided too many times?
In that case your plan would be treating the symptom, not the cause (accumulated genetic errors and whatever other junk in the stem cells). I would also expect it to lead to cancer.
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).
That sounds interesting, but I can't find it. Can you quote the part of that paper you are talking about?
The speaker is one of the PI’s on the project so it is worth watching the whole thing. I can’t find the paper again where the delayed ageing is mentioned, but the speaker does talk about it - far more offhand than it should be for my liking.
It is pretty easy to ff through a scientific talk because of the slides, but if you are just interested in the Brazilian mutation then start from around 6 minutes.
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... ), and the SENS Research Foundation has been funding the necessary research to address ALT ( http://www.sens.org/research/introduction-to-sens-research/c... ), 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...
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.
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.
This approach is how evolution has solved the problem of cancer in large animals with long lifespans.
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"
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.
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...
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...