"lifespan, not just healthspan, has to stay central to aging research" - @aubreydegrey

In science-fiction post-human civilizations - such as the Culture or the Forerunners from *Halo* - discussions about the economy seem to have nothing to do with the amount of value an individual contributes to that economy. Quite the opposite. The focus is on how much the economy is willing to spend to protect a person and their life - sums that are astronomical compared to the value that individual actually contributes. In those settings, the economy exists to preserve life and expand the capabilities of conscious beings. A rough formula: Value = Resources / Output. Value = the value of a life Resources = the amount of resources the civilization is willing to spend Output = the benefit derived from the individual Below 1: utilitarian civilizations. Lives are expendable resources for capital. Above 1: post-utilitarian civilizations. Capital is an expendable resource for lives. We are here together because we want to tip the scales.

AI excels at maths because it excels at brute-force methods, allowing it to receive rapid feedback. This opens up a new frontier - extending beyond "wet labs" - to frame problems in physics, chemistry, biology, and materials science as maths challenges that can be empirically verified. Beyond cryopreservation, I believe we should look at reformulating problems in mathematical terms and searching for biocompatible materials. Incidentally, the my company in spinal cord reconnection project is essentially a form of wound reprogramming - a process that is also conceptually amenable to mathematical modeling. Same for “how to find the ideal candidate” in my TalentRiver. Transforming poorly defined problems with long feedback loops into tasks where the quality of the solution can be evaluated at low cost - that’s the profession of the new age.

The whole work on simulation of fullbody reversible cryopreservation for humans can cost less then a single round of the company focused on animal experiments. And it can also give way more insights in what can and can’t work. And also can simplify and better direct each next step. We literally can solve 10 yrs of work in 1 year and start asking way better questions to biology.

You won’t believe it, but here is the solution space for the problem from the previous post. 1. Cryoprotectant loading has basically turned into a race between two rates: the delivery rate - how quickly it reaches all cells; the damage rate - how quickly the body deteriorates without normal circulation. Both slow down as temperature drops, and we actually don’t know which one slows down faster. What we do know is that at 4°C, we need roughly 135 hours for loading to reach avascular tissues. 2. While replacing the blood, we will need to load the body with some kind of Sacred Fluid capable of sustaining metabolism. This fluid would need to: - carry oxygen and useful metabolic substrates at normal temperature; - protect against cold injury; - carry the cryoprotectant at its working concentration; - remain fluid and mutually compatible throughout the entire loading range. Ideally, the cryoprotectant itself would be non-toxic at normothermia. Alternatively, the fluid would need to remain low-viscosity for a very long time. No existing solution currently does more than two of these things at once. It is possible that instead of one universal fluid, the answer is a continuous, compatible sequence of different fluids. 3. What needs to appear in the world? Normothermic organ perfusion using a fully synthetic, cell-free perfusate, sustained for days without significant damage. Cell-permeating cryoprotectants that are non-toxic at normal body temperature. Today, we essentially have the opposite. We need to determine actual damage thresholds. Right now, these are known mostly for transplant organs and, occasionally, for specific vessels after infarction or stroke. Most cryobiology literature tells us “how much survived” rather than “where exactly it breaks.” 4. Caveats The entire hypothesis may still be killed by the vasculature. If the vascular network fails, reversibility fails with it. Intervertebral discs may not actually be the worst-case tissue for loading. Some functions of the perfusate may be transferable to other systems. Our requirement of 95% coverage cannot yet be declared necessary - but neither can we simply replace it with 80%. Overall, we are not particularly happy about this route. Our goal was to prove impossibility, and at this point we have only pushed the impossibility boundary further away. Or maybe we are quietly happy about it. Just so nobody notices.

Here is an example of a set of constraints for reversible cryopreservation that I find *very* promising (in terms of closing / resolving). To preserve you, we need to perform a "loading" process - saturating your entire body and cells with a cryoprotectant solution - which requires a significant amount of time. However, there are strict limitations: - We cannot load too quickly; if the volume of the cells changes too rapidly as they take up the cryoprotectant, it will kill them. - We cannot raise the pressure too high, or we risk damaging the blood vessels or their lining. - We cannot take too long with the loading process, or the lack of metabolic activity will cause irreversible damage to the body. - While lowering the temperature might seem like a way to buy time, we cannot drop it below the point where fluid viscosity begins to rise, as that would make the loading process take even longer. Liquid Load Lock 🤪 Let’s see what i’ll do with it

Essentially, the reversible preservation modeling pipeline: - Experimental data (both external and one's own) are needed to validate the simulation. - Simulations generate data for the theorem. - The theorem defines requirements for the protocol, liquid, and tools. - The cryoprotectant selection funnel matches the liquid to the protocol.

You are protected from death only as good as cryopreservation well and reliably established where you live. That is the baseline. Everything else is essentially quality of life.

In essence, reversible cryopreservation comes down to the following questions: Does there exist a delivery schedule under which the target concentration of solution and particles is reached at every point in the body, while intracellular fluid loading, shear stresses at vessel walls and tissue-environment interfaces, and pressure remain below damage thresholds? Does there exist a cooling trajectory under which every point in the body vitrifies at the achieved local concentration and does not fracture during cooling? Does there exist a storage regime under which, throughout the entire storage period, no point in the body fractures, undergoes flow or structural relaxation beyond acceptable limits, or develops ice? Does there exist a method of warming to the point at which a liquid phase reappears such that, at every point in the body-including regions distant from blood vessels or containing gas-tensile stress remains below the local failure strength? Does there exist a warming method that allows every point in the body to pass through the onset of liquid-phase formation without generating damaging tensile stress? Does there exist a subsequent warming trajectory under which, at no point in the body, the ice fraction exceeds the allowable limit, while the warming rate and spatial nonuniformity also remain below thresholds that would cause irreversible damage? Does there exist an intermediate state at which the process can be paused and accumulated damage can be compensated for or repaired using available interventions? Does there exist a solution that satisfies all of the above requirements, including eventual removal from the body, such that residual concentrations remain below acceptable toxicity thresholds? Does there exist a complete protocol in which the combination of all preceding requirements - and the body passing through all of these states - does not introduce additional forms of damage?

@theseusbio rising soon breaking your spinal cord should not be the end

So, regarding the reversible cryopreservation. First, we need to prove that reversible human cryopreservation doesn't violate any physical, chemical, engineering, or biological limitations. To do this, we'll put together a proposed procedure plan and draw a computational graph based on it. The graph should answer just one question: "Is it possible?" with three answers: YES, NO, I DON'T KNOW. And we'll calculate in 2 versions: if the graph is optimistic: "IF I'M LUCKY, IS IT POSSIBLE?" And if the graph is pessimistic: "EVEN IF I'M UNLUCKY, IS IT POSSIBLE?" Optimism is cheaper to calculate than pessimism, but if even optimism fails, then calculating pessimism is pointless. I already have a plan and partially a graph. Considering that it will contain 10^3 - 10^6 points, the AI ​​will do everything. To protect against AI laziness, each formula must have a reference, a citation from it, and a hash as proof of its validity. The graph's connectivity and quality is calculated by the validator. The runnet gives back the result. Ideally, reference values ​​should be concentrated as much as possible in the graph's inputs. Meanwhile in the graph's inner layers, the reference values ​​can serve as a reference (but it's important to indicate the conditions that occurred). If the calculation diverges from the reference values, that's great - it means we've stitched something together somewhere in physics, chemistry, or biology and can unstitch it. Any "no" kills the graph version, and the procedure needs to be improved. A side effect of the graph is that I'll know under what conditions the answer is "YES." But I'll likely lack the numbers for the minimum synapse integrity, the minimum water content in cells, and the acceptable cytoskeletal injury.

Our preprint is out 🚀 In mice, sequential VEGF-A165 plasmid + AAV9-follistatin produced stronger local muscle hypertrophy than AAV-FST alone, with ~2× more capillaries and no treatment-related safety findings through Day

the scientists are scared to work on it the influencers are claiming they already solved it the biotechs are optimizing everything around it the investors are funding anything that avoids confronting it the supplement companies are selling distractions from it the conferences have stopped talking about it the entire field has surrendered to it it is death few are left trying to defeat it

My dad died, and I'm not ready to talk about him. What I can say is: FUCK DEATH. FUCK AGING. FUCK CANCER. FUCK ALL DISEASES. Why do y'all (99.99999%+ of people) just sit there and pretend the situation is ok? Yes, I know you might have been programmed to accept it. To see the "beauty". Bullshit. Classic Stockholm syndrome. We DO NOT have to accept involuntary death, aging, diseases, suffering. Do not go gently into that good night. Rage, rage, rage against the dying of the light. Fight, fight, fight aging & disease. With science. Medicine. Yes, we can. Youth. Limitless health & life. And it's worth trying. Don't be afraid to get your hopes up. If it doesn't work out in our lifetime, we at least will have tried, and we will have advanced medicine for the next generation to be free from disease. Btw: there's no true freedom without freedom from disease.

Euthanasia program might reduce suicide rates among those aged 70+. Sweden doesn't have one; the Netherlands does. But even in the Netherlands, where euthanasia is most widespread, in 2024, people aged 80-84 committed more suicides than any other age group per 100k people. Surprisingly, in most Western countries, older people have similar or higher rates of suicide compared to younger people.

Death should be optional. If you want to do something about it, check out my new book Radical Life Extension: Technological Strategies to Defeat Aging. ❄️🫀🧬