I agree that brain rejuvenation should be a priority (but alas we live in a world where rejuvenation of any kind is not a mainstream priority). But I feel like all your examples miss the mark? Head transplants just move the brain to a new body, they don't do anything to reverse the brain's own aging. The other examples in part II are about trying to migrate the mind out of the brain entirely. What about just trying to rejuvenate the actual neurons?
If you look up brain rejuvenation, the most effective thing known seems to be young blood; so I guess Peter Thiel was on to something. But for those of us who can't or don't want to do that, well, this article has a list of "twelve hallmarks of mammalian ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis". Logically, we need something like Aubrey de Grey's SENS, tackling each of these processes, specifically in the context of the human brain. And I would start by browsing the articles on the brain at fightaging.org.
I think the point is being missed here, I'm saying if you solve aging at the level of a head now body-transplant becomes viable, otherwise you're indeed just stuck with an old mind.
As for parabiosis approaches, the sens take, etc -- My personal take is that it's hogwashy, biology is a faulty paradigm that hasn't yielded relevant results in 80+ years, primary gains in solving diseases come from diagnosis criteria being shifted, gains in mortality reduction are solving at the mean not at the edges (e.g. removing pollution, better ERs, broader vaccine and antibiotic distribution, reduction in youths dying, reduced childhood mortality -- stuff that is a distribution and production problem as of 100 years ago, not a scientific venture)
I don’t know if author will even see this comment, but beyond the mainstream theories of antagonistic pleiotropy and damage accumulation, the reader may find it interesting to explore the concept of programmed aging as an adaptation to combat pathogens. IMHO, this is a better example to defend the position than thymic involution, because it makes a much stronger case for the existence of a 'program'.
A framing I quite like is that of germs vs soma, body vs eggs and cum, consciousness vs replicators.
My first foray into age reversal was a (successful) attempt to increase fluid IQ, the loss of which is among less than a handful of ubiquitous symptoms of aging.
At the time, I found it odd that most people working in biotech, medicine, and longevity were confused about why I did this.
In part, the issue here is one of people finding it hard to break out of existing paradigms, even as hypotheticals. The limits of my language mean the limits of my world. (I expand more on it in this talk)
In part, I believe the medical, biotech and even longevity community are misguided about what goals are worthwhile to achieve.
Reversing the aging process is one of the most lofty goals achievable within our century, and a necessary stepping stone for humanity. Very few people, if any, are interested in this issue; Most end up working on curing diseases or minimally prolonging life in old age. (More on this later)
I believe these two parts are linked and socially caused; We have a tendency to copy each other, and we have incentive chains pulling people towards patentable narrow-effect drugs and therapies. And when corrupt incentives pull people for long enough, we oft forget about the chain and think of it as "just the way the world is".
Let me stop with digressions: assuming you fall into neither of these pitfalls you might still be confused as to why reversing the mind's aging ought to be the most (only?) relevant problem in longevity.
When discussing eternal youth, a framing I quite like is that of germs vs soma, body vs eggs and cum, consciousness vs replicators.
Many things are desirable individual traits when it comes to natural selection giving rise to ape populations in and around the Congo. Such desirable features include proclivities to age, rape, die, murder, and go infertile.
Humans distinguish themselves among primates by being able to break to the "meta" level of the natural selection game using a "mesa" optimizer (big brain =>more food, less death, more kids).
It's only incidental that these brains allow us to contemplate our condition and give rise to the fundamental question "What the fuck is going on?". (We start caring about everything else)
All good people are concerned with this question at the level above one individual (Gods, AIs, societies, cultures, “the economy”, etc), why are the structures we exist in so suboptimal for the flourishing and happiness of individuals? Individuals are stuck in these replicating constructs dictating their movements and affecting their experience – These constructs are necessary, almost axiomatically so – but their self-generating and self-perpetuating nature makes them suboptimally designed with regards to human happiness.
However, few of these people realize that a similar runaway process is going on within them. For whatever reason our bodies are adapted to interact with the environment in ways that slowly kill us. This is desirable from a selection point of view, the processes of aging allow us to preserve resources (thymic involution, synaptic pruning), to gain efficiency; Genes optimize for spreading efficiently.
Yet, we are not the genes, we are the soma, the body, the electromagnetic processes ongoing within and on top of the CNS, giving rise to the experience in which the I is found, together with everything else.
But really, what I care about is this “experience” thing. My sensation of I (or whatever you chose to replace it with), the “outside world” (or rather, the simulation of it within my experience), my perceptions of the body, feelings, emotions, and sensations.
There is never any salience or experience around my sperm.
There’s a bit of it around various internal organs.
There’s a lot of it around my toes, forehead, genitals, hands, eyes, ears and nose.
And the way my brain “integrates” all of this into a “simulation” that seems to contain my body (even though it’s happening within its bounds) – oh boy, not only is there salience and experience there, salience and experience happens “within” that thing.
So another narrative can arise, similar to soma vs germs, body vs eggs and cum, and consciousness vs replicators, and it sounds something like “mind vs matter”. The ability of this cloud of experience, this complex electromagnetic process, to shape the material substrate running it to one more amiable to our well-being.
Rest assured I will not venture to postulate anything as naive as an ability to replace the brain with circuits neuron by neuron or to “upload” the mind onto any state-machine, be it quantum or classical. (If you are experiencing confusion as to why this is silly, I encourage you to read some of Michael Edward Johnson’s explanatory works)
Indeed, I am not sure what to do with this information, except to note that it seems pivotal in the quest for age reversal. It narrows down the things that we truly want to focus on.
There are several “mind-preserving” interventions that could reverse the process of aging. In brief, they are:
The ability to transplant heads onto clones lacking a central nervous system (e.g. human bodies developed in vitro without heads), while vulgar, is a pretty reliable way to reduce the complexity inherent to the problem of longevity.
Transplanting a head is relatively trivial, the biggest issue being spinal cord grafting. Happily, this is a problem that’s being worked on as part of addressing spinal injury.
By far the bigger issue is producing human clones without a central nervous system.
When most people talk about head transplants they refer to anencephalic clones, omitting to mention that “anencephalic” is one of those words we’ve suitably redefined to mean something else than its components. Sadly enough humans don’t develop without a central nervous system, not even without a brain, they can develop without a large part of the brain but that is insufficient to make mass-producing such clones ethically safe - a hill I’m sure I’ll have plenty of fun dying on later in life, together with the most repugnant of allies and a few good friends.
That being said, allowing a clone to grow to the size of a small child without a central nervous system, or at least without a brain and the upper part of the spine – seems like a solvable problem. It’s probably a “Manhanat project” problem in terms of scale, but it conveniently forces us to understand the brain a lot better in order to replicate its functions during development, thus killing two birds with one stone.
The interventions besides head grafting are pretty far-flung, and thinking about them won’t yield much. But, I believe it’s good to go through them in order to add some more meat to my previous claim, i.e. that you really only care about “yourself” as in “experience” as opposed to some abstract wholistic notion that includes your body exactly as it is now or as it was in the past.
In this paradigm, the only “open” problem for addressing longevity in our lifetime becomes preserving the head. Or rather, the bits of it that we can’t really replace; Eyes, lips, bones, and tonsils are not of importance; What really matters is the brain and the spine. To be more specific, the glia, the neurons, and the vasculature permeating the structure.
Now, I will grant you, this is a pretty hard problem. Indeed, vasculature and neural tissue are the trickiest of fuckers; And if we manage to understand how aging can be reversed in these tissues; We’d like to have the ability to maintain the rest of the body alive via techniques that are more akin to organ replacement.
Still, I think head transplants are a more “clear-cut” way to conceptualize the role of heads as the sole object of study the field of longevity should care about. If you are doing thymic regrowth, or bone marrow rejuvenation, or liver regeneration - good on you, and have fun - but you are not tackling the critical problem of aging.
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On the more “science fiction” side of things, understanding how the mind works would allow us to gradually transfer our bodies onto more suitable substrates.
I wrote about this idea when I was a kid, and I find no other suitable source to cite to give you a deep intuition here; Recommendations are welcome, I’m sure someone else has had this thought.
The gist of it is that one could slowly transfer various functions of the central nervous system onto materials that are external to the body, either linked to us or embedded within us, validating that something that feels “meaningfully like myself” is preserved each time.
This sidesteps the hard problem of consciousness, since both the valence and existence of experience are confirmed by the now 1% more cyborg individuals that were previously in a state where such a thing had been confirmed or axiomatic.
This approach doesn’t even require us to understand the brain, just how to interface with it well enough in order to allow it to offload function.
There are some tentative attempts at this underway, but they are slow, dangerous, and expensive – requiring the removal and grafting of neurons after a long period of suppression in order to allow an area’s functions to be remapped onto other areas, then mapped back onto the newly grafted tissue – it’s also a rather lossy approach. Furthermore, such an approach means that the underlying substrate remains the same, neuronal tissue, and thus it doesn’t do much to address aging.
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The wildest of approaches is transfering the entire contests of experience/consciousness via a bridge of sorts. This, in principle, doesn’t require us to know anything about the brain, but it does require us to know a lot about the mind (i.e. the dynamic process running “as” or “on top of” the brain).
Such an approach is squarely in the realm of fiction novels, and even so, I can think of only one semi-realistic portrayal of it.
You can imagine something akin to a neuronal bridge, implanted in various parts of your brain, through which you “access” and “configure” neuronal tissue external to you (think of it as clumps of neurons in a vat) into “shapes” that allow your mind to move onto it and abandon your current brain.
I’m giving this example since I wanted to demonstrate the full axis of head to mind.
An approach that requires us to understand nothing about the mind, just how to keep the head young (transplant).
An approach that requires some knowledge of the brain and some knowledge of the mind (gradual transfer).
And an approach that is hypothetically doable by treating our head as a black box, but likely requires a very good understanding of minds and the kind of substrates that can host them.
Maybe “something something AI” comes about and human cognition becomes irrelevant, but I think there are ample worlds in which this doesn’t happen, and fascets of human cognition that are critical to doing science are not easy to fully replicate, let alone surpass, and AIs are collaborators or tools that still require humans. This is certainly the case now, and I think most people agree it will be the case in a decade or two, so let’s focus on that.
In such a world, the fact that fluid intelligence decreases with age, starting in one’s teens or early 20s. “Fluid intelligence” is a humorous word we invented to refer to anything and everything that doesn’t involve memorizing words and relations between words - Thus it would encompass the ability to spot patterns, move your body, react to events, solve mathematical problems, and do any sort of complex modeling that is impossible or slow in the verbal realm.
We observe this as becoming increasingly “specialized” as we age, closed off to new ideas, unmotivated, guarded with regards to what we are willing to pursue and entertain, preferring known security to explore the unknown, and “not understanding the kids these days” while the kids these days seem to perfectly understand us (at least sufficiently to build the mind-control algorithms dictating the moves of their parents and grandparents via social and networked media).
An economy that’s built around having young people “prove themselves” in their 20s, to provide them with more and more resources as they age is counterproductive to solving any new problem - and age reversal is certainly new, there are no agreed-upon paradigms or even clues around how it could be done.
You could try fixing economics, but I tend to agree that society is fixed and biology is mutable. In aggregate, we should try fixing the economy, as individuals and small groups we should focus on what might be doable: Giving people more runway to be smart by reversing or stopping brain aging.
I’m not certain that reversing the brain’s aging is doable, but it certainly seems like a much better candidate than any other system that comprises the body, if one is allowed to use this fuzzy separation.
My own experience with this has been that a trivial approach (get more blood to the brain, when tissue has more blood tissue grow when the brain has blood-brain grow), yielded pretty good results. This approach likely has very fast diminishing returns, and I doubt the results are very permanent; But it showcased the amount of low-hanging fruit that people are oblivious to.
The fact that low-hanging fruit exists and that there is a lot of money to be made from understanding the mind, both in terms of enhancing existing humans and treating cognitive decline - makes this field rather juicy.
Doubly so since the typical “RCT validated drug” approach continues failing miserably at putting even a dent in diseases associated with brain aging - probably because the disease<->aging link is too strong in order to address the former without doing so for the latter.
Thus, solving brain-related “medical” issues might forever remain a free money-printer for whoever figures out age reversal in this organ.
More important than that, is the fact that brains are particularly prone to a fast-feedback-loop approach to understanding them. It is relatively trivial to act upon the brain and ask “What did this intervention do”, because, to a frist approximation, the mind is rather aware of what’s going on with the brain.
We certainly have some awareness of the rest of our bodies, but the density of sensing-capable cells in the brain and surrounding structures is a thousandfold that of any other parts of the body.
We don’t take advantage of this because we haven’t started trying to understand how various states our brain is in “feel like” - but there’s certainly a possibility we could be conscious of things as fine-grained as “right now my hippocampus is producing a lot of progenitor cells” or “there’s a lot of activity in my Broca”. After all, our fingers can sense 13-nanometer-tall bumps, so I see no reason why our brains couldn’t detect things as fine-grained as the movements of a single axon.
Of course, “I feel this is working” is no ultimate proof for any intervention, but it’s a great sieve to figure out what doesn’t work, and an intuition builder for what might be going on before we engage in any expensive imaging.
We do ultimately need wholistic imaging, which is slow and expensive, like MRIs or MEGs; However, being able to “feel” various changes in the brain would make it easier to validate things and also allow for the training of much faster imaging devices, much like the fNIRs or CETI devices we have at present.
The other side of this coin is that delivering “free energy” to a small area of the brain and seeing how it reacts is also a relatively trivial issue; After all, neurons are capable of commanding a vast array of cells to do their bidding (both inside and outside the brain) so we need only learn how to speak the language of neurons, how to convince these cells to do what we tell them, and they will handle coordinating everything else that needs to happen.
The way we command neurons might look like using focused ultrasound, near-infrared laser interference, or specifically shaped low-intensity electromagnetic fields.
But combining these approaches can result in very fast feedback loops, where we test 1001 shapes of particular interventions in a live subject in minutes or hours - Moving at a pace of iteration dozens of thousands of times faster than current medical science - With result validation via slow imaging techniques and physical engineering work as the only bottlenecks.