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... (read more)
100% agree the messaging should focus on health rather than lifespan - not only because it's far less controversial (most people want to be healthy), but because it's true: we work directly on health, of which longevity is but a side effect. Glad you picked up on the multi-morbidity part too, tackling age-related sickness as a whole by focusing on fundamental ageing damage rather than treating diseases separately is crucial. Probably we'll be talking about morbidity compression for a while yet; this is a crux that allows us to discuss medicine that actually works without having to acknowledge the Biblical-scale consequences of it. At some point though, laboratory results will become so compelling that the delusion collapses, and then all hell will break loose.
If it turns out healthspan aligns well with longevity
It can't not. People don't die because they get old, they die because they get sick.
It's both prevention and cure - prevent disease by reversing damage before it gets bad enough to cause problems, but if you already have a chronic disease, then reversing the damage that causes it will be the only way to cure it (though prevention is better of course).
I agree the preventative medicine angle is a good one that people will buy easily, but you can make the same argument against it - that we've always been trying to prevent disease just as we've always been trying to fix damage.
It's important to note that statins, blood thinners and rapamycin are not damage repair - they're not useless, but I think damage repair will... (read more)
Always glad to see Greg Egan referenced. The important thing to me is that although population growth could be exponential (for the reasons cousin_it gave), it's going to be very slow relative to the rate of technological progress. Unless fertility rises significantly, it's likely to be hundreds of years before population would grow by 10x, by which point we're well into Greg Egan territory and all bets are off anyway. So population could be a concern, but we'll have plenty of time to address it via methods that don't involve literally everyone dying.
Yes we've always been trying to fix damage - anything that restores function must fix damage somehow - but it's a matter of what we consider to be damage, i.e. "bad stuff that we should try to fix because it would restore function". Historically we've focused on trauma, infection and cancer, and although we've known about age-related changes like lipofuscin accumulation for a long time, it's only recently that we started thinking of them as potential targets. Gerontology has historically been a field of basic science, with few gerontologists willing to venture that we could even in principle do something about age-related changes until very recently. They were too afraid to challenge... (read 419 more words →)
If we define damage as material defects, which I think is closer to your original intent, then maladaptative memories (of the affective system in PTSD, of the pain system in CRPS, of the immune system….) can cause a loss of function without a lasting role for material damages
"Material"? I don't think it's useful to distinguish between material and immaterial change, the point is that the change is maladaptive. If your hard drive gets corrupted preventing your computer from booting then we still call that damage, even though it seems less material than, say, shooting the PSU. And ultimately, data and code are material anyway, whether they're represented by patterns of magnetic polarisation or changes to neuronal sensitivity or connectivity or whatever.
You may well turn out to be correct - biology is indeed fiendishly complex and still very poorly understood, and it may turn out that clearing the damage types identified by the SENS platform is insufficient for comprehensive rejuvenation. However, I've tried to separate that particular claim from a different, more defensible, more immediately relevant one: that damage repair should become our main approach to medical research in a world where infectious disease is largely conquered, and most suffering is due to (mostly age related) chronic illnesses. Most bodily disorders these days are caused not by infection by an external pathogen, but by damage to the body itself, most of which is... (read more)
The one that always come to mind is: how will we spare space for the youths?
I'm unusually chill when it comes to population, both over and under. I'm not enormously concerned by how many people there are, I'm more concerned by how healthy the existing people are, and how healthy the environment is, both of which are mostly orthogonal to population and depend primarily on technological development. It's important to note that fertility rates are generally declining worldwide, seemingly in tandem with economic development. The most economically developed countries generally have below-replacement fertility rates, and are facing depopulation plus highly inverted population pyramids (high ratio of sick, dependent, aged people) if something... (read 672 more words →)
There are papers showing senescent cells in humans with signs of shortened telomeres and replicative stress (e.g. [1,2]), so I wouldn't say the Hayflick limit is nonsense or irrelevant in humans. But there is perhaps a broader point that the Hayflick limit / telomere erosion has been over-hyped as the fundamental driver of ageing. Case in point, I once talked to a guy who told me "Immortality is impossible, because: telomeres".
The problem is that telomere erosion tells a simple and compelling story about what ageing is, like every cell has a built-in clock that prevents us living too long. From skimming the article, the point Ray Peat seems to be making, in... (read more)
I’d like to live in a world where age really is just a number. For the last ~3 years or so, I’ve been nerding out with increasing fervour about longevity biotech, having originally been inspired by one of Aubrey de Grey's many interviews. I want to explain how and why I've become optimistic about the short-term prospects of indefinite healthy life extension, in terms of how I've come to think about ageing, disease, medicine and rejuvenation.
A revolution is underway in how people think about health and medicine. Worst case scenario, it will unlock a whole new generation of therapies that can actually cure chronic age-related diseases, instead of just moderately slowing their progression... (read 12109 more words →)
- 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
... (read more)