The Senolytics section comes across a bit like all senescent cells are bad so if we could just kill them all we’d be doing a good thing. But my understanding is that they also play a role in healthy body functions. Is that also your understanding here?
From what I’ve read, the healthy roles they play are a) during early/embryonic development and b) in wound healing. So, don’t give senolytics to embryos or people healing from wounds I guess. Also, there’s a paper (summary here) showing that it’s possible to regain the wound-healing benefit of SCs in mice that are engineered not to create SCs, just by manually applying a single growth factor that SCs secrete into wounds. So it seems unlikely that the beneficial roles of SCs are a show-stopper, particularly because those beneficial effects are more associated with short-lived SCs rather than the ones that linger and accumulate.
Largely related to the above, the framing of the post seems that of body as a machine but I’m wondering if that is the best framing. Perhaps body as a ecosystem might be better. I don’t think it changes any of the main points you make (that I’ve read) but perhaps suggests following the machine metaphor might be limiting, and in some cases point in the wrong direction. Does that seem right to you?
I find it fascinating to think of the body as an ecosystem (e.g. cells competing for resources, occupying niches), but I use the machine analogy because it emphasizes that there’s an overall structure and function that can be degraded. What does it mean for an ecosystem to age or decline, how do you define the health of an ecosystem?
You can imagine an ecosystem <---> machine axis, where it’s more like an ecosystem when you have independent entities competing for their own survival, and more like a machine when they work more closely together to act as one. In this sense, I think metazoans are both ecosystem and machine. But much if not most of the damage that drives ageing is at the level of individual cells rather than whole organism, and it makes more sense to think of individual cells as machines.
One way in which the ecosystem view is helpful is that it emphasizes that dead or damaged cells (e.g. senescent cells) can be destroyed and replaced by the division of healthy cells. That’s something you couldn’t do in a non-ecosystem-like-machine, such as a car, and it’s a major benefit—replacement of old cells by new is really the best form of damage repair since you “repair” all the damage at once that way.
Indeed—people are finally thinking “what if ageing has something to do with all the age-related disease?” This is great, so long as you remember that “ageing” is not just one single root cause of age-related disease; rather, it’s a multitude of self-inflicted injuries the body slowly accumulates, which combine to make us frail and disease-prone.
Simulations of that fidelity level would indeed be ridiculously powerful tools, but I don’t know how long it’ll take to reach that level. Also, with a true full-body molecular simulation you’d have the ethical problem that a simulation at that level of detail is for all intents and purposes a human being, and may no longer be ethical to experiment on. The strength of damage repair as a medicinal paradigm is that it exposes a whole host of targets that we can safely go after, confident that doing so will improve function without having a full understanding of how the body works. Often we try to treat disease by changing the way the body works (e.g. statins), but this is very hard to do without side-effects because of how complex and inter-connected the body’s systems are. But the things I call “damage” are age-related changes that are unambiguously bad for you and can in principle be reversed. Doing so might not cure all age-related diseases, but it should prevent them all, since by definition they tend not to occur in people who don’t have a lifetime of age-related changes.
People are absolutely applying the centaur-intelligence thing to ageing already (e.g. Gero, Altos, In Silico), indeed I think all current applications of AI are working in synergy with human intelligence, and I hope it stays that way for as long as possible. It’s good that we are indeed able to benefit from (what currently passes for) AI long before it reaches the level where we can just ask ChatGPT “how do I cure ageing” and it just tells us.
What matters here is what we want. For now, I quite enjoy being made out of meat, and I think most other people do too. Our desires are what they are, and they don’t require justifying, to AGI or to anyone else. Of course, such transformative alterations/extensions to our selves will no doubt be unlocked one day, and I could happily live in a world where people modify themselves in all sorts of different ways, one step at a time, on their own terms, as and when they feel like it.
It’s almost certainly me that’s wrong here—there have been lots of different IFRs quoted so I picked 2% as the highest I could remember hearing, just to be conservative. Lower IFR would strengthen the argument I was making there, and indeed the true number is almost certainly much lower due to e.g. asymptomatic infections.