11 ms·
Since it seems like the upshot of all of this is that Katcher is claiming to have discovered a set of signalling molecules which, when injected, rejuvenate tiss
by maxander 6y ago
Since it seems like the upshot of all of this is that Katcher is claiming to have discovered a set of signalling molecules which, when injected, rejuvenate tissue and presumably lengthen life, it runs into one of the most fundamental objections that can be leveled at theory of aging (or cure thereof): of the billions of humans that have existed, how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment? In the case of this proposal this sort of objection is particularly strong, since (though the blog post is silent as to what the treatment is) it's given that they are fractions from blood, so they're substances which the body produces in some quantity anyway, and which are sufficiently non-dose-specific that Katcher, with limited resources, could devise a reasonably effective regimen.
Parabiosis is one of the most striking (and just weird) phenomena in aging research, so efforts to understand what's going on with it are liable to bear interesting fruit. I'm just pointing out that there's good reason to doubt that this particular "breakthrough" is the "cure."
- putlake 6y agoPeople who had this mutation could have died of causes other than aging.
- commandlinefan 6y agoMy first thought too - maybe it's just wishful thinking, but the bible does talk about people who lived for thousands of years. We're prone to dismiss this as hyperbole from uneducated ancients, but maybe they actually did exist and this sort of thing was why.
- jjoonathan 6y ago"Someone slipped up the distinction between years and generations and a legend was born" still seems enormously more probable than anomalous longevity existing but somehow never making it into the wider gene pool.
- pbhjpbhj 6y agoDo you (they) mean "distinction between years and months"? That would be between solar cycles and lunar cycles: seems enticing. That would make Methuselah 80yo when he reportedly died; but there are problems still as Seth (for example) became a father at 105, which if it were months would be 8¾ years. Another possibility is that when it says Methuselah it just means "Methuselah's blood line" or "Methuselah the tribe"; it's a Hebraic thing (elsewhere in the OT) to refer to a tribe as if referring to the founding person. Or, the person writing down the numbers used a different system, through error or otherwise.
- jjoonathan 6y agoYeah, they would both account for being off by a factor of 10-20. As would any of a dozen other simple mistakes or embellishments, in all likelihood. IIRC the Skeptic's Annotated Bible has a bunch of direct numerical self-inconsistencies if one needs proof that this sort of slipup is possible, which one shouldn't, because of course it is.
- holtalanm 6y ago> the bible does talk about people who lived for thousands of years I don't remember anyone mentioned living for _thousands_ of years. There are plenty of characters that live for hundreds, though. It is believed that Abraham lived to the age of 175, while I believe there was one character that lived into the 300's, but I do not recall their name. It has been a while since I delved into the old testament.
- lm28469 6y agohttps://en.wikipedia.org/wiki/Methuselah https://en.wikipedia.org/wiki/Methuselah > Said to have died at the age of 969, he lived the longest of all figures mentioned in the Bible.
- holtalanm 6y agothat name rings a bell now that I see it. thanks! edit: Found it on the wikipedia page you linked. I was thinking about Enoch, Methuselah's father, who lived to be 365 years old according to the bible.
- twodave 6y agoInterestingly, Methuselah died the same year that the Flood happened, so you might assume he would have lived longer had his grandson not been instructed to build a party boat that he wasn't invited to...
- Cactus2018 6y agoNota bene, lunar year vs solar year
- Unknown_Unknown 6y agoI believe in Islam Noah is believed to have lived 950 years. It took him a long time to build the arch. The other story mentioned in the Quran is about a group of people and their dog who slept in a cave for 309 years and woke up afterwards. I believe they died shortly after. There is an actual chapter in the quran about this called the cave[1]. [1] https://www.clearquran.com/018.html https://www.clearquran.com/018.html
- SketchySeaBeast 6y agoOn a long enough timeline, can't we assume that pretty much everyone is going to die of cancer?
- TheAdamAndChe 6y agoElephants are massive, and have a very large number of cells compared to humans, yet their rates of cancer aren't higher than ours. Research indicates that it may be due to TP53, a cancer suppression gene that is repeated a ton in the elephant. I could see anti-aging therapy eventually being used in conjunction with gene therapy to strengthen our own tumor suppression capacity.
- James_Henry 6y agoThe body, when it is healthy, generally kills cancerous cells on its own. This is, from what I understand why many cancers come with sickness/age, because your body doesn't react as robustly to broken cells as it did in health and youth. Something like "age reduction" could end up being a cure for many cancers, one could think.
- SketchySeaBeast 6y agoGiven that there are cancer's that strike the young as well, I don't know if that would actually work out.
- bovermyer 6y agoPeople who are immune to aging are not necessarily immune to a cannonball impacting their face.
- Nevermark 6y agoIf only we could subject enough people to cannonballs we might find one of the super humans I postulate exist. But train wrecks would allow for significantly higher populations per experiment. I must ponder this. They call me Mr...
- eganist 6y agoAt risk of sounding absolutely insane: There's probably no way to prove that this hasn't happened. Anyone who realizes they're not aging normally would likely have taken on a new identity elsewhere for fear of: 1. being burned at the stake 2. being trialed in repeated experiments 3. being deified, and then subsequently being burned at the stake. --- I realize my comment sounds like a joke, but I'm entirely serious. If you or I found out we're not aging normally and look e.g. 25 by the time we reach 40, or 30 by the time we reach 45, would either of us remain in our current lives?
- throwaway1777 6y agoThere are other things that can cause similar effects. Many people look “younger” than their age.
- throw_away 6y agohttps://en.wikipedia.org/wiki/The_Man_from_Earth https://en.wikipedia.org/wiki/The_Man_from_Earth
- parentheses 6y agoOne of the only movies that remains intriguing throughout despite being basically a single conversation.
- castlecrasher2 6y agoJust don't look up the sequel.
- fortran77 6y agoWhat about "My Dinner with Andre?" That's exactly a single conversation. And so is, mostly, "Rope."
- Supermancho 6y agoI happen to love certain niche movie genres, which happens to include "dinner party movies". Feel free to list some recommendations, if you like "people talk in a room" movies. Some of my favories: Coherence (scifi) Garden Party (sleazy young adult Los Angeles drama) Murder Party (low budget horror comedy) How English sounds to non-English speakers (youtube) Circle 2015 (scifi)
- waynecochran 6y agoEvolution may not select for long life? https://biology.stackexchange.com/questions/17077/why-does-evolution-not-make-our-life-longer https://biology.stackexchange.com/questions/17077/why-does-e...
- rantwasp 6y agothis is the right answer. once you reach reproduction age and you are able to reproduce, from an evolutionary point of view you're done.
- sterlind 6y agoEh that's too simple in humans. Hanging around longer to tend children and pass on knowledge benefits the survival of your grandchildren, who carry your genes too.
- rantwasp 6y agoyes. you need to reproduce and to ensure your offsprings reach sexual maturity. but humans are in no way special. we believe we have escaped our biology because of the cultural stratum we posses (ie exchanged memes for genes) but we are still basically animals.
- hammock 6y agoWhy couldn't it be true that we want to survive to ensure our grand-offspring and great-grandoffspring reach sexual maturity as well? That's a valid strategy (with tradeoffs, as there are with everything)
- rantwasp 6y agowe definitely want to survive, even with 0 offsprings. That was not the point. The point was the natural selection does not optimize for the longest surviving humans.
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- lm28469 6y agoIt all boils down to "is living longer an evolutionary advantage ?"
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- pelario 6y ago> how is it that none of them have possessed a mutation which (...) endogenously produced the signalling molecules which Katcher is proposing as treatment? Because evolution is a random-driven process. (in the same way that we carry a number of traits that made our survival harder)
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- gmaster 6y agoDeath and aging is a feature of evolution. These features evolved to further enable evolution and allow it to iterate more quickly. Species that iterated more quickly, and therefore evolved more quickly were more successful. Features that are deliberately evolved exist within many different genes as a mechanism to protect the feature, this is why dropout works so well on neural networks.
- pharke 6y agoI wouldn't say a feature of evolution. Perhaps it is an adaptation of sexually reproducing multicellular life but it certainly doesn't apply to all life.
- gmaster 6y agoJust like organisms evolve things such as vision, frontal lobes, etc, we have evolved aging because it ultimately positively impacts the survival of species. This makes it an evolved feature, wouldn't you say?
- glenstein 6y agoAre there any good articles or books that make this case in a form that's not a just so story? You're just kind of stipulating that it's beneficial. I think it's more likely that, as many others in this thread have observed, longevity is ignored while evolution optimizes for other things, which I would distinguish from something that specifically evolved like vision. Things can die perfectly well on their own without dying needing to be optimized. It would also be more plausible to me that death was evolved if it had some clear, functional, deliberate mechanism by which it was enacted, the way that eyes or lungs are clearly purposeful and functional. Death happens as an interference with function rather than as someone handled by an organ or internal system.
- gmaster 6y agoThe quantity of a particular species in an ecosystem has an equilibrium point. The optimal amount of a particular species is a number. If there's no death, this number will be pushed out of equilibrium, and the given species isn't dedicating its niche in the ecosystem to the most superior 'version' of itself, therefore not investing the niche resources in the best bet of progressing the species. This is more than speculation, how is this not beneficial?
- yohann305 6y agoLet's say someone possessed that mutation. You have to remember prior to 200 years ago, your chances of dying from a disease, an accident, hunger, race, religion would have killed you anyway.
- AnthonyMouse 6y agoEven today this is true, from different causes. If you eat too many cheeseburgers you die of coronary artery disease before you die of old age. Anybody can still get into a car accident or get cancer. Even minor injuries can result in infection or blood clots. Every meal is another chance to get food poisoning. Maybe the people who don't age just died of something else eventually.
- platz 6y agoSo you can live longer, but what about cancer?
- James_Henry 6y agoMaybe living longer means you don't get cancer. There are animals with extremely low or even zero rates of cancer.
- hackinthebochs 6y agoTo put it simply, a population with aging is more fit than a population without. The speed at which beneficial mutations in a population reach saturation in the gene pool is a function of the number of generations that have gone by. So we can expect some downward selective pressure on lifespan.
- CameronNemo 6y agoAt that point you are getting into some of the same reward dynamics that you see with honesty in intra-species signaling. Particularly that an organism in a population may wish to signal honestly even if it knows it is unfit so that the overall population health can improve. From what I recall, many evolutionary biologists disliked the hypothesis, instead preferring the costly signaling theory as an explanation of why signals remain honest. https://en.wikipedia.org/wiki/Signalling_theory https://en.wikipedia.org/wiki/Signalling_theory
- ativzzz 6y agoSo then, once a population reaches "ideal" mutations, if that is possible, then wouldn't the opposite start happening?
- downerending 6y agoThere is no static ideal. The total environment is incessantly changing, and organisms are constantly adapting.
- nardi 6y agoI'm not an evolutionary biologist, but why wouldn't the selection pressure be related to the speed at which offspring are produced, and not the age of the parent? And why wouldn't a parent that lives a long time and thus produces more offspring be evolutionarily fit?
- hackinthebochs 6y agoThere are a lot of factors involved in having viable offspring. For example, you need enough resources to sufficiently feed and nurture the children you already have. So having more offspring than some ideal amount for the environment can be detrimental. But parents also compete with their offspring for resources. Aging and dying is eventually the best thing a parent can do for their children.
- cbanek 6y agoMaybe because people tend to reproduce fairly early in life (usually half of lifespan) so living an extra X years doesn't really allow you to have more children, and therefore the mutation of longer life doesn't get a huge enough advantage in natural selection?
- glenstein 6y agoRight. And I suppose that the other side of the same coin is that we might want to deliberately delay having children as long as possible if we were actually trying to steer evolution toward optimising for longevity.
- entee 6y agoThere are tons of reasons this wouldn’t have happened. Lots of this is speculation but: Seems likely this is a gradient, not a binary thing, so perhaps someone with a beneficial mutation would just live a little longer. There’s not a ton of evolutionary pressure at the old age side of the spectrum, you’re not reproducing a lot, so it may not get picked up. Wilder speculation: it could be that indeed this has been happening and is why humans live about 2x as long as chimps and gorillas. Personally I think it’s quite unlikely that in humans single genes would have large deltas on age. There are maybe a few hints from supercentenarians (https://en.wikipedia.org/wiki/Research_into_centenarians https://en.wikipedia.org/wiki/Research_into_centenarians) that telomerase and other genes have some effect, but the “one gene for aging” in humans is elusive. As a result, it’s hard to predict how all this would play out evolutionarily.
- lalaland1125 6y agoI would be very careful about trusting research on supercentenarians. There is a substantial amount of evidence (https://statmodeling.stat.columbia.edu/2019/08/06/are-supercentenarians-mostly-superfrauds/ https://statmodeling.stat.columbia.edu/2019/08/06/are-superc...) that a significant number of "supercentenarians" are simply pension/tax frauds taking up the names of dead people to keep collecting pensions.
- entee 6y agoEntirely possible! Hadn’t heard that critique but makes sense and something to control for.
- CerealFounder 6y agoYup, your "hot take" is the core of "Lifespan" by Dr. David Sinclair.
- ken 6y agoWe don’t know it’s zero. What fraction of humans who have ever lived have died of old age? We could have age-proof people living among us today who happen to die in car accidents or any number of other causes.
- lkbm 6y agoSeems like having this mutation from the beginning might be very different from getting it when you're 20+. Would you simply fail to develop even to viable infant stage?
- tantalor 6y agohttps://www.bbc.com/future/article/20140520-the-girls-who-never-age https://www.bbc.com/future/article/20140520-the-girls-who-ne... > A handful of girls seem to defy one of the biggest certainties in life: ageing. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest. He suspects that the disease is caused by a glitch somewhere in the girls’ DNA. His quest for immortality depends on finding it.
- riggins 6y agoI'm sad this comment hasn't been upvoted higher. The comment explain how the mutation could be possible. The key is that the mutation would prevent reproduction. If you never age, you never reproduce. You can think about different cancers. A mutation that causes fatal childhood cancer doesn't get passed on. A mutation that causes prostate cancer can spread.
- James_Henry 6y agoAging/death and reproduction seem to be closely related. I suppose maxander would counter that some mutation, given the many people who have lived before, should preserve reproducibility and youthfulness if fractional plasma is able to, but I'd counter that maxander is measuring (or guessing really) the probabilities wrong.
- Supermancho 6y agoI met a child-like animator, who worked for Disney in Anaheim California (tiny hands). He appeared somewhere around age 9 at his mid 20s, due to a pituitary dysfunction from a car accident.
- strbean 6y agoFor a high-profile example, see Andy Milonakis[1]. He is ~40 in this video. https://www.youtube.com/watch?v=hb9UgsVDwI0 https://www.youtube.com/watch?v=hb9UgsVDwI0
- entee 6y agoImportant caveat for one of the patients mentioned in the article: “Her telomeres were considerably shorter than those of healthy teenagers, suggesting that her cells were ageing at an accelerated rate.“ Aging is weird. Maybe there’s something to be learned from these cases, but it’s very unlikely to be straightforward. Unless you’re a roundworm. We can make those live hundreds of human-relative years. But in those cases it’s a tiny number of genes involved, we have near zero evidence that the same is the case for higher organisms.
- ben_w 6y agoIt has happened, and there are multiple documented cases. At least, the effect has happened — I don’t understand biology well enough to know if any have the cause described in the article. https://en.m.wikipedia.org/wiki/Brooke_Greenberg https://en.m.wikipedia.org/wiki/Brooke_Greenberg
- chubot 6y agoI think Jared Diamond had a similar argument that seems valid. Roughly speaking, it boils down to the fact that you need 90 out of 100 subsystems in your body to be working. Your lungs, your heart, your skin, your brain, etc. They interact, but each part also needs to work on its own for you to live. Every one of those systems can fail and leave you dead. Since evolution only "cares" about you to the point where you bear children and raise them, what are the chances that it engineered ALL those systems to last FOREVER? And then it created a single hormone to control every system and make them stop decaying? Such a fantastic over-engineering can't occur purely by chance, 100 times over. ----- In fact ANY mutation that decreased life expectancy but increased fitness during the reproductive years would be selected FOR. So it seems possible you have multiple mutations that prevent you from living much longer than "expected". (I'd even conjecture there's a sexual selection effect going on in the "live hard die young" people, like rock stars, athletes, etc. Their hormones are selected for "living on the edge", and that strategy has proven useful over millenia... i.e. a tendency toward self-destruction is not necessarily something that gets weeded out by evolution) ----- That said I think it's definitely possible for some treatment to make someone who would have lived 60 years last until 70, or even 100. It's harder to imagine going from 100 to 200 (especially with productive life).
- restalis 6y ago"Every one of those systems can fail and leave you dead. Since evolution only «cares» about you to the point where you bear children and raise them, what are the chances that it engineered ALL those systems to last FOREVER?" Evolution works in small steps, over long periods of time (given the humans slow grow up process). Mutations in any of those systems may increase or lower the chances of such failure. Evolution takes care of both, albeit by a small margin. Currently, cause of death number one worldwide is the ischemic heart disease¹ (i.e. the famous "coronary"). Now guess what, there are genetic mutations that work on this out there already, one of them being the Gilbert's syndrome². Yes, forever is unattainable, but (humanity scale speaking) I'm glad having lived past twenty four and willing to take any blessing coming after. "I'd even conjecture there's a sexual selection effect going on in the «live hard die young» people, like rock stars, athletes, etc." I hope you're aware of survivor's bias here. Assume a lot more of those to be weeded out. Also, the stars made it not only because they were risk inclined but also because they they have that value they were recognized for. I find the gradual improvement that one may gain having a bit of time to be a very useful edge over the young and inexperienced, in the game of life. Especially for a male (that is not that restricted by an inherent fertility age limit), this edge fits perfectly in the reproductive selection window you mention. ¹ https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death https://www.who.int/news-room/fact-sheets/detail/the-top-10-... ² https://en.wikipedia.org/wiki/Gilbert%27s_syndrome#Cardiovascular_effects https://en.wikipedia.org/wiki/Gilbert%27s_syndrome#Cardiovas...
- etrautmann 6y agoIt would have to confer benefits before reproductive age in order to be a trait for which there's evolutionary pressure (to first order). Something that makes you more likely to live an extra decade almost certainly won't make you have more kids or make your kids more likely to survive, so there's no selection pressure for those genes.
- epicureanideal 6y agoUntil recently, I assume even a human with an anti-aging mutation would've been killed by something else within a typical lifespan. War, disease, lung damage from wood burning stoves or coal, injuries while working, and so on. Also, if it takes 4 different mutations (assuming each of 4 injections is a different substance), it might be very unlikely for all 4 to happen in one individual, and any 1 mutation may not give that individual any particular reproductive advantage.
- all_blue_chucks 6y agoEvolution only cares about whether you have viable offspring. Beyond that longevity could be a harmful feature because the long-lived would be competing with the fertile individuals for resources.
- kbenson 6y ago> of the billions of humans that have existed, how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment? How would we know? What fraction of people in the past actually dies from old age and complications of old age, and not disease, infection, or strife such as wars or other conflict? In the past, I imagine not degrading due to age would be at best an extra few decades of time until you got a bad flu, or pneumonia, or an infection, or were killed on a battlefield, or if you were female, died from complications of giving birth.
- cgiles 6y agotl;dr: this is not an "age reduction breakthrough", it is both A) a confirmation of what we already knew, which is that parabiosis makes old mice healthier, and B) a finding that virtually proves the mAge clock has nothing useful to say about lifespan Parabiosis does not substantially extend lifespan (possibly not at all), based on the experiments done so far. Even if it did, it definitely does not double it, which is what would be predicted by naively looking at the halved DNA mAge on the clock. This paper is very likely intended as another validation of Horvath's mAge clock. The clock shows that there is a strong association between epigenetic state and both chronological age and morbidity risk. Exactly why that is, and what it means, is highly controversial. Mainstream aging field does not really care about lifespan much anymore. Increasing amount of focus is on so-called "healthspan" - approximately the duration of healthy life, or incidence of morbidity. You would think that you could not affect one without the other, but in fact you can, to a frustrating and surprising degree. Therefore when you read about "rejuvenation", we are increasingly finding that you can find treatments which improve a broad spectrum of unrelated health markers, that these treatments will affect epigenetic loci predictive of age, and all of this without any substantial effect on lifespan. (From a public policy perspective, this is considered highly desirable, as for public expenditures it would be ideal if people lived perfectly healthy until the moment they keel over, even if we cannot extend the time until they do) One possibility to keep in mind is that rodents die almost entirely of cancer. So it is possible that some treatment which improves "everything except cancer" would not show any lifespan effect in rodents. This would be one way of reconciling this paper with Horvath's earlier finding that the clock predicts all-cause mortality in humans.
- lend000 6y agoWhile the article mentions the current paradigm (accumulated DNA damage as the prevailing view of why our cells slow down), it doesn't address how it is wrong. In which case, cells with the right signals will behave more actively, but this could also lead to faster onset of cancer. A more interesting approach to me seems almost feasible with current technology, assuming CRISPR will soon be able to replace DNA without causing more side effect DNA damage than it fixes. Take a healthy human blastocyst, derived from healthy young relatives of the patient (likely to have compatible mitochondrial DNA). Now, determine the patient's original DNA structure. This would occur by sampling various cell lineages and using a statistical model to estimate the original DNA of the patient as a baby. Now, take some stem cells from the blastocyst and replace the DNA with the patient's DNA. Generate a culture of different stem cells and inject them throughout the patient's body. The patient now has cell lineages with fresh telomeres that will be actively dividing for another 6 decades. Perhaps additional signaling regulation would be necessary to prevent types of growth that would be unwanted in adults. Any experts want to poke holes at this idea? I have no formal training in biotech but I always thought this seemed like the cure to non-structural age related diseases. The harder part seems like cleaning and regrowing new veins and arteries, and brain repair.
- nikanj 6y agoNot aging doesn’t mean not mortal. Until very recently, old age did not make it high on the top causes of death. Not aging doesn’t really help against hunger, illness, and accidents
- ignorantguy 6y ago"The man from the earth" movie comes to mind reading this. Should have ctrl+f 'ed before commenting. It's a great movie.
- busyant 6y ago> how is it that none of them have possessed a mutation which (in this case) endogenously produced the signalling molecules which Katcher is proposing as treatment? FWIW, I'm pretty skeptical of this announcement, but (assuming it's correct), it's possible that you need multiple signalling factors to achieve the age-reduction and that one single mutation might not do the trick. Let's say that you needed four precise mutations to achieve the age reduction, then the probability of getting all of them in a single individual would be quite low. But like I said, this announcement has a bad smell to me. In particular, the fact that they are not revealing the "rejuvenating factors" as well as the fact that they have not demonstrated age prolongation. Finally, the complaint about the aging field being focused on cellular damage feels a little "straw-man-y" to me. I'm certainly not an expert in the field, but I imagine there are numerous researchers hunting for age-related signalling molecules.
- kerkeslager 6y agoWell, the obvious explanation to me is that that did happen, and then the person died of some cause unrelated to these specific signalling molecules. Possibly another cause of aging. In 1850 the leading cause of death in the US census was "zymotic diseases" and cancer caused death in the triple digits. In 2020, almost none of the diseases in the "zymotic" category are significant in the US, but we're still dying. We've cured croup and scarlet fever, so we don't die of those much any more--instead we live long enough to die of heart disease and cancer. Cancer didn't kill many people in 1850, but that's only because "zymotic diseases" killed them before they could develop cancers.[1] I think it's likely that there are many causes of aging, and they will behave the same way: as we eliminate some causes of aging we'll live long enough to die of other causes of aging that take longer to potentiate. Given most people who reproduce do so before the age of 50, there's not really an evolutionary pressure to not age--in fact, there may actually be evolutionary pressure to age so you die off and leave more resources for more efficient (younger) organisms carrying your DNA. Ghengis Khan, the most evolutionarily successful person in history, died at 64 or 65. So if a person did produce these signaling molecules, they wouldn't necessarily gain any evolutionary benefit from them. [1] Obviously "zymotic diseases" is a nonsense category in modern medicine--most were bacterial infections, some other forms of infections, some completely misattributed to infection. The point here is that most of them weren't cancers or heart disease--the things that kill Americans today.
- ajuc 6y agoSome people could have had that molecule, but it might have been undesirable for long-term survival of their tribe.
- erikpukinskis 6y agoLiving a long time could be advantageous for the individual but disadvantageous for the society. Evolution happens at all scales, not just the creature scale.
- JoeAltmaier 6y agoBecause, immortal creatures are counter-adaptive. They become a load on their population as they accumulate injuries and disease damage, until they are an ancient hulking parasite on their line?