#61

I actually think I’m more optimistic on how science, technology and medicine will evolve in both the next 10 years and decades thereafter and how that could enable longevity escape velocity scenarios than most people here on forum.

Below are some extracts from some recents posts by me.

At the same time, life is so incredibly important that I think the world needs to work on multiple paths - and there could definitely end up being massive road blocks to age reversal via molecules, partial reprogramming and other gene therapies.

Given that - and that value for most of all types of disease that leads to human suffering could be solved by replacement strategies - and while there are some big challenges to achieve full-blown, perfected replacement capabilities, the scientific risk there seems smaller than in solving most disease and aging via other paths, I think the world should work to enable replacement strategies as fast possible.

Partially because I think it might be the only way to save people who are decades older than me, partially because of diversification and that it’s smart to invest in things that are likely to work.

I’m not sure I would call replacement a back-up plan though. Rather it might be the stepping stone that gives people some extra 3-4 decades to then be able to access other types of rejuvenation that might take longer time to get there.

(Biostatis I would call a back-up, but a crucial one to perfect as fast as possible so people in my partners generations might have a path to avoid oblivion)

Examples of me arguing that there is a real probability for outcomes ahead of with rapidly accelerating progress and hence real scenarios where humanity can reach longevity escape velocity:

cannot reach the answer by [just] analyzing current or historical speed and progress rates of science, technology and medicine.

Rather we need to base the analysis on things such as what the world’s capabilities for scientific and technological learning and progress will look like…

Personally I think the evidence for scientific, technological and knowledge capabilities growing along exponential paths and along linear paths is quite strong. So the world’s technological and scientific progress during the decade from 2050-2060 might very well be an order of magnitude larger than all the process we have seen the last 50+ years from 1970-2023.

And

Btw - for someone who is less “hype focused” and has delivered quite massively scientifically to the world here is a perspective Prof George Church of Harvard and the Broad Institute yesterday

… quite amazing stuff

Helps one understand why he thinks that longevity escape velocity night not be that far off.

He was recently quoted as below

Professor George Church of Harvard Medical School echoes a similar timeframe.

According to Dr. Church, “The exponential technologies that have improved the speed and cost of reading, writing and editing of DNA and gene therapies, now apply to the category of aging reversal.”

*He adds: *“I think age-reversal advances could mean that we reach longevity escape velocity in a decade or two, within the range of the next one or two rounds of clinical trials.”

So, what does that mean?

Can we extend the healthy human lifespan past today’s record of 122? Can humans live past 200 years? Or even indefinitely?

And when “defending” Bryan Johnson

he is trying to answer the question:

  • what if control of aging already is possible - but with the totally of the knowledge needed spread out among many hundreds of thousands different papers and studies - but holistic protocols have just never been put together and tested for real to leverage that understanding to its full potential
  • (and the corollary - what if, even if we not are there yet, we are approaching the point where above will be true - eg in 5 or 10 or 15 years)

…believe there is some real probability that human kind might reach full longevity escape within either this or the next generation - and he’d really want to have a chance of being part of that.

In that context taking some risk that things in his protocol combined may shorten his life by say 5-10% (or do you think he is risking more than that?) might be worth it if he believes it might buy him even just a very, very small probability increase of intercepting longevity escape velocity and perhaps adding 100s or 1000s of % to his life span (and seeing a future that he seems to believe will be much better and have more powerful experiences than the present).

And again on how I optimize things to increase probability of reaching longevity escape velocity:

If one is instead is optimizing for longevity escape velocity and/or think one either has less risks of sarcopenia/osteoporosis and/or think that one is young enough that good interventions for frailty will come online in time before becoming frail (eg myostatin gene therapy type of things) then one may want to lean more towards the second path.

#62

I’ve mostly been saying

A. If you in steps provide new, young healthy brain tissue to a declining brain, there are reasons that that healthy brain tissue will integrate with the brain and overtime take onboard function and become part of the redundant storage of memory

B. If the world does not have to invest in treating most of the disease that occurred in the rest of the body because that has been solved by (brainless) clones replacement parts the resources and scientists that will focus on solving dementia and other brain aging and diseases will accelerate rapidly

C. Almost whatever the state of a brain, I will likely do better and decline slower in a young, new body than in an old body

Do you disagree with any of (A), (B) and/or (C) above? If so, would to hear what part(s) you disagree with and why

#63

None of A, B or C contradicts my point.

A is a separate process for brain repair. It may work.

B ia clearly wrong. Brainless clones and transplant is a massively resource intensive process as well as raising ethical questions. Just developing brainless clones is likely to be harder than solving aging.

C is probably true, but does not fix a demented brain.

I think i understand the basis of most of aging and how to mitigate that, but even if i didnt i think the whole body replacement strategy is not one i would spend time on.

2 Likes
#64

For anyone motivated to keep their brain young, other than the stuff that you already do, I highly recommend any kind of racket games: tennis, table tennis, badminton or pickle balls. Some studies said it may extend healthspan by 5 years.

Screenshot 2024-10-11 at 9.25.40 PM
Screenshot 2024-10-11 at 9.25.40 PM1704×526 200 KB

https://www.mayoclinicproceedings.org/article/S0025-6196(18)30538-X/abstract

3 Likes
#65

You’re right and I know that from following your posts. It was more a question of priorities.

There’s a certain area of longevity that I view as more “fringy” so when I talk to my friends about taking metformin or rapamycin for longevity, I avoid talking about the fringy things because I want them to take me seriously. As Pfleger said, “Backup strategies are CRYOpreservation, mind UPLOADing, & whole-body REPLACEment (brain transplant).” That’s what I consider fringy. Interesting, and I’m not against them in principal but they are still more like science fiction. Until it’s possible in mice (forget C Elegans), I just don’t have time for it, there are plenty of more practical solutions that I’m spending my time researching.
**Following your discussion of the brain with John, I agree that if you freed up resources from other research, it would progress faster. But why put body replacement 1st and then move the resources to the brain? Brain science actually seems to be accelerating now with new discoveries and understanding coming at a rapid clip. I wouldn’t want to divert any of that attention to body replacement.
My point is that it’s fine and good for the big thinkers to be talking about these “backup” strategies but as a practical matter we should focus the money where we can get results quicker.

1 Like
#66

Thanks @John_Hemming - I think I now see where we the areas of disagreements are (in category B and less in A and C).

I believe below may be less problematic that it seems you feel they are (notations in [] are mine).

I’ll reply to each. So I can do so in a good way can you clarify what ethical questions you might feel are problematic in this context?

#67

If we simply look at how you could develop brainless clones that is a good start. First to avoid the major ethical questions you would need to have a clone develop without a brain, but otherwise functional. There would still be more minor ethical questions as arguably a person’s identity is not just in the brain. Obviously developing a clone with a brain would raise a major ethical question. However, what about the CNS in the round is the CNS part of the clone’s identity and rights as a human.

However, lets for the moment leave the ethical issues and consider the practical ones.

a) Get a clone embryo,
b) grow the embryo in an artificial womb,
c) take the embryo out of the artificial womb and grow the clone to an adult state whilst keeping it in a living state as otherwise it would be no good for transplant.

There are so many technical challenges in that.

You then have the question as to how to transplant the brain. The eyes are part of the brain. There are nerves around the the body. They are arguably part of the CNS.

I think it is true that a clone embryo could be created. The rest is really difficult and resource intensive.

1 Like
#68

As long as you guys are talking about “replacement” and “rejuvenation” you should watch this short presentation by Omri Drory on Renewal Bio. I covered Omri’s presentation last December at the Longevity summit, see here: Highlights from the 2023 Longevity Summit - #8 by RapAdmin

4 Likes
#69

I think your first one here was one of the biggest scientific and technical barriers - that now to a large extent may be behind us

I 100% agree that this part is crucial - and for decades after cloning Dolly the Sheep there was a big question whether it would be possible to clone primates, including humans.

So the primate cloning breakthroughs in recent years totally changed the prospects for cloning enabled replacement strategies, see for example:

IMG_8942
IMG_89421179×1237 69.6 KB

IMG_8941
IMG_89411074×690 82.2 KB

https://www.science.org/content/article/these-monkey-twins-are-first-primate-clones-made-method-developed-dolly

and

IMG_8944
IMG_89441179×959 97.4 KB

IMG_8943
IMG_89431179×1045 86.2 KB

Medical researchers would find the genetic standardisation which cloning brings useful, especially if it could be applied to the two species of monkey—crab-eating and rhesus macaques—that are the mainstay of non-human-primate research. And if monkeys with clinically interesting genetic modifications could be mass-produced, it would be even better.

In 2018 Dr Sun made headlines by bringing to term and raising two cloned crab-eating macaques.

The following year, he and his group performed the same trick with five genetically engineered crab-eaters.

Now, they have managed it with a (non-genetically modified) rhesus macaque. As they reported on January 16th, in Nature Communications, they have in their institute a healthy, two-year-old cloned male rhesus.

And in creating him, they may have invented a better way of cloning monkeys in bulk.

And the scientific paper from January of this year:

https://www.nature.com/articles/s41467-023-43985-7

3 Likes
#70

The other two are less scientific or technical risk, and while would need logistics, actually would have solutions based on todays capabilities:

That could be one way of doing it. And there is some meaningfully investment into that for the purpose of saving human baby after preterm births.

See for example

IMG_8945
IMG_89451179×942 109 KB

IMG_8946
IMG_89461179×1012 82.6 KB

IMG_8947
IMG_89471179×1420 101 KB

There are several other ways also that seem inline with what bioethicist have felt is ok in somewhat similar contexts - for instance testing genedited pig organs in deceased brain dead human organ donors (so called decedents). Such donors could perhaps be the carriers of the first brainless clones. And then brainless clones could be the carriers of future brainless clones.

This would organizationally probably be not be that crazy complex. More careful care it’s done all around world with people in long term comas. And in some states in the US families have the right to keep a family member “breathing and heart beating” (for years and decades) even after medicine has determined the family member to have lost ability for future consciousness due to sever brain damage).

—

Not saying that things will be a walk in the park by any means.

There are a lot of things that need to fall in place, including new science and technology that needs to be developed.

But it does seem like this is more like going to the moon or mars - a big undertaking, that human civilization with very high probability could solve if we decided too. And less like curing all cancer or solving aging via molecules and gene therapy - the size of those challenges is more uncertain.

2 Likes
#71

A fascinating issue and discussion…I’m learning as I go along. Just as a good introduction, I looked at Wikipedia…

Somatic cell nuclear transfer

This technique is currently the basis for cloning animals (such as the famous Dolly the sheep),[30] and has been proposed as a possible way to clone humans. Using SCNT in reproductive cloning has proven difficult with limited success. High fetal and neonatal death make the process very inefficient. Resulting cloned offspring are also plagued with development and imprinting disorders in non-human species. For these reasons, along with moral and ethical objections, reproductive cloning in humans is proscribed in more than 30 countries.[31] Most researchers believe that in the foreseeable future it will not be possible to use the current cloning technique to produce a human clone that will develop to term. It remains a possibility, though critical adjustments will be required to overcome current limitations during early embryonic development in human SCNT.The biochemistry involved in reprogramming the differentiated somatic cell nucleus and activating the recipient egg was also far from understood.Epigenetic factors play an important role in the success or failure of SCNT attempts. The varying gene expression of a previously activated cell and its mRNAs may lead to overexpression, underexpression, or in some cases non functional genes which will affect the developing fetus.[44] One such example of epigenetic limitations to SCNT is regulating histone methylation. Differing regulation of these histone methylation genes can directly affect the transcription of the developing genome, causing failure of the SCNT.[45] Another contributing factor to failure of SCNT includes the X chromosome inactivation in early development of the embryo.

This was very interesting, but lacking any detail. Amazing, the mention of using CRISPR to manipulate the mouse embyo to develop without a head, would love to know how they did that.

#72

People are thinking about this already; its not as hard as you might think, and the cost is “only” $60 Million to $160 Million… see this video:

1 Like
#73

This is something where we disagree. There is nothing wrong with people disagreeing.

I would add the point, however, that

This inappropriate treatment of PVS patients costs around £90,000 per individual per year.

There is a resource question as well as lots of ethical and practical questions.

2 Likes
#74

Brain transplant might be indicated for many politicians-nobrainers (pun intended).

What about elaborating a bit more on mitochondrial transplants/mitochondrial transfusions:
Europe PMC and correction of one of the graphs:
Europe PMC

infused mitochondria seem to reach the CNS.

When produced from multiplied harvested stem cells this may actually rejuvenate this vital part of the cell. Correction of faulty parts of the mitochondrial DNA by crispr-cas or treatment with medication in vitro before infusion may be of additional value for some.

Cost and risk should be way less then a full stem cell transplant.

#75

There are quite a few mitochondrial transfer approaches as well as endogenous improvement systems eg Rapamycin

#76

This feels like a generic answer like: there are a lot of publications out there so go and find out yourself…

My guess would be that mitochondria are less immunogenic and may be there species other than human that can produces mitochondria on a massive scale that are biocompatible for large groups of the human population. Mitochondria that may be stored in DMSO ??% in liquid nitrogen.

Sofar treatment of dementia, ALS to name some has not been proven unequivocally successfull.

You might know a lot more than I am able to read and comprehend…

1 Like