Age Reduction Breakthrough?
joshmitteldorf.scienceblog.com
joshmitteldorf.scienceblog.com
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."
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.
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.
> Said to have died at the age of 969, he lived the longest of all figures mentioned in the Bible.
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.
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].
But train wrecks would allow for significantly higher populations per experiment.
I must ponder this.
They call me Mr...
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?
And so is, mostly, "Rope."
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)There's some play adaptations which have few characters and mostly dialogue: Carnage, Who's Afraid of Virginia Woolf, Glengarry Glen Ross
Linklater's "Before" trilogy is also heavily dialogue-based, but the there are multiple locations.
"Perfect Strangers" (2017) [1].
Although I didn't realize until I commented that Jerome Bixby the author of The Man From Earth was also a Star Trek writer.
[0] https://twitter.com/synopsi/status/1188295183130955778?s=21
As for more extreme cases, I could believe that a few people discovered that they weren't aging and hid it, but not more than a few people, especially in modern times. Switching identities isn't exactly easy and the probability of every one of them successfully carrying it out gets exponentially suppressed as the number of people increases.
FWIW, it doesn't need to do this. It just need to result in more surviving children and grandchildren. Looking 5-10 years younger when you're a female between the ages of 25 and 40 could A) get you access to a higher status mate who can better provide for your children, and/or B) keep your mate more interested in you, reducing the likelihood that they will continue to provide for the children you have with them.
When the team went on an offsite morale event jet skiing, he was told by the proprietor that he couldn't participate because their policy requires you to be at least 16 years old. He was 27 at the time. He never lived that down with his peers. When he tries to go to a bar with friends, he's sometimes accused of trying to pass off a fake ID. These experiences are deeply embarrassing for him.
Imagine trying to get promoted to a senior director position at a company while looking like you are fresh out of college. In that case ageism takes a different meaning.
I recently worked on overhauling the reporting system for one of the largest police departments in the US, and every step along the way I was asked who was in charge, how did I enter the workforce so young, how I got an internship while attending high school (I had already graduated college), etc. I even got those types of comments from other employees at companies where I worked full-time. Of course, I don't really have the luxury of getting too offended by it all the time, otherwise I'd be really bitter, but the classic "Oh well you'll be glad you look young when you're older" gets tiring.
You have to be careful not to come across like "a suit" in the engineering circles, it's a tricky balance, but it's worth it.
My Dad is in his mid 80's and plays four hours of sports a day, or at least he was before the pandemic hit.
When I was in my mid-20's I had to impress the hell out of potential clients to get work, as I looked like I was 15, and girls my own age wouldn't look at me as I was too young. I never drank, so bars weren't an issue. When I was in my early forties, 15-20 year old girls were still coming on to me. I will be 50 next year, and I finally look like I'm in my 20s or 30s, and still get those looks from University-aged girls whenever I venture where they hang out.
A couple of years ago, my now 43 year old partner was mistaken for her teenage doppelganger and asked to the high school prom by three different boys while walking home from work.
It was annoying earlier, but now I look forward to turning out to be one of the immortals.
Pretty sure I saw this movie in the 80s.
In general I’ve seen a lot of people that look young for their age but when looking at their skin up close on their face, neck or hands it gives it away. Women are also at an obvious advantage through their use of makeup.
I've read that when Scott McNealy met his future wife (they married when he was 40) she thought that he was a Stanford undergraduate.
"You look so young."
"I have this portrait in my attic."
We did a Dexa scan a few months back and it put her age based on body composition at 14.
She gets annoyed about it sometimes as she feels people don't treat her seriously. Because of this she's quite conscious of what she wears, and how she presents herself.
For anyone curious you can find her on youtube - search "Good Paleo Life"
It was nice. I can't grow facial hair though so I have no choice. What worries me is when I'm 45, I'll look like the world's oldest 30 year old or something.
It's rather fun for me and I enjoy these kinds of interactions. Can't say it really ever hindered or embarrassed me in any way.
I suspect that if those people who feel embarrassed because they look young were looking older, they'd find something else to be embarrassed about. It's easy to find any number of shortcomings with yourself.
So, if you want to tell if someone is 25 or 40, maybe their skin will give it away?
There would almost certainly be a continuum, perhaps following a power law. The top quartile might be the "40 not looking a day over 25," while the top 0.1% might be true Dorian Greys.
I was routinely told I looked 25 at the age of 45, and can assure you I felt no need to start accumulating secret identities.
Go take a look at her photo.
https://www.washingtonpost.com/local/at-107-this-artist-just...
But yeah, wow.
I once met a 102 year old man who lived alone in a big patch of private forest in BC that he bought in the '20s. He was still driving a car and doing jumping jacks.
"The Ouroboros, an ancient symbol depicting a serpent or dragon eating its own tail, has been said to have a meaning of infinity by depicting the cycle of birth and death. The Ouroboros eats its own tail to sustain its life, in an eternal cycle of renewal."
Waiting for my deification now...
Not aging is as slow as aging, and by the time you realise and accept there is something special with you, everyone else around has already figured it out. Disappearing at that point might be a pretty conspicuous move "that guy [or woman, I wonder why all immortals must always be men... :)] who is 70 but actually looked thirty went missing".
It's about a very small number of people who are immortal, in the sense they stop ageing at 25 (iirc). They can be killed like anyone else, but smaller damages do heal faster. Also, they never get sick. Some are thousands of years old, some less. Some smart, some not so much. How they handle their immortality is very interesting though. I won't spoil it for you though.
[0]: https://en.wikipedia.org/wiki/The_Boat_of_a_Million_Years
Excessive smoking and UV light exposure can easily make a 25-year old look older than a healthy 50-year old who exercises regularly, uses sunscreen when they go out in the sun, and didn’t get scars from accidents.
The Man From Earth and its sequel are on Amazon Prime Video.
edit: I should have did a ctrl+f man from earth
It's a great show everyone seems to have seen it. I never knew about it until I saw it in my Amazon Prime Video suggestions.
https://en.wikipedia.org/wiki/List_of_people_executed_for_wi...
Quite a number were burned for (obviously alleged) witchcraft. (grep page for 'burn')
That's where I derived that first bullet.
Of course that was hard to prove or disprove, but we have examples of alleged witches accepting payment for harming/killing other people using whichcraft - like a contract killer. So at least the intention to cause harm was there in some cases.
There are numerous accounts of people having (alleged) supernatural abilities who was not persecuted, e.g ascetics surviving without eating for years and such. These were generally held in high regard, and could end up as saints.
Of course people could be accused for maleficium on really flimsy evidence so it could also hypothetically happen to the hypothetical slow-aging person just like it could happen to anybody else.
> Of course people could be accused for maleficium on really flimsy evidence so it could also hypothetically happen to the hypothetical slow-aging person just like it could happen to anybody else.
Yep, hence points 1 and 3.
Thanks!
My point was just that unusual aging patterns would not put you at any particular risk of being burned at the stake.
And the same argument applies to true magicians btw.
When you could summon real magic, why should you reveal that to others?
(or care to claim a million dollar
https://en.m.wikipedia.org/wiki/One_Million_Dollar_Paranorma...
)
But I doubt it.
From a perspective of evolution, aging and dying and new borns, make sense, because the environment changes. And youth is able to adopt better to new changes.
The socially desirable scenarios like this aren't really the interesting ones. How about looking 5 when you reach 25?
Let's assume the mutation happens when the person is in their 20s, which would be ideal. If this occurred any time in history up to the 1800s, would you not still be likely to die of disease, cancer, or other injury? Life expectancy hasn't increased because we are better at slowing aging, it has increased because we are better at not dying of the things that kill us.
If the mutation happened invitro, did the child survive birth? If it did survive but never grew, it wouldn't reproduce, and may have been abandoned if it were too much of a burden.
There are many scenarios where this mutation could have occurred but was never passed on.
Aside from that, it's only in the last millennium or so that we have record keeping that we could plausibly consider credible enough to prove the existence of such a person - in ages before that we have countless myths of immortality or unnatural longevity that we immediately disregard as fictional. So if Methuselah really had lived 969 years due to this mutation, we'd all be none the wiser!
>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?
1, 2 and 3 are very astute observations about human nature. ALL people who disagree on 1,2 and 3 are just naive in what they think human nature is. History repeats.
https://biology.stackexchange.com/questions/17077/why-does-e...
This will sound callous, but some older people really should be allowed to die. There's definitely points of diminishing returns for all involved; I hope that under certain conditions (eg dementia) I'll be allowed to die when I'm decrepit.
Because evolution is a random-driven process. (in the same way that we carry a number of traits that made our survival harder)
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.
This is more than speculation, how is this not beneficial?
Maybe the people who don't age just died of something else eventually.
Meanwhile if there was an entire community like this then the people living longer still wouldn't be at a disadvantage, the community would just have a different equilibrium. The surviving communities could e.g. have fewer children on average (you only have to replace people who die in accidents) or would expand their territory over time (expanding population can control more territory).
But if everyone lived longer than required, i.e. the minimum ideal for raising viable offspring, then this population stood to be out-competed by another population that aged at a more efficient rate. Individuals in a population aging at an optimal rate is an evolutionary advantage to the population.
Are you trying to provide an evolutionary justification for aging by using aging itself as a reason?
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) 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.
We could have age-proof people living among us today who happen to die in car accidents or any number of other causes.
> 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.
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.
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.
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.
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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)
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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).
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-...
² https://en.wikipedia.org/wiki/Gilbert%27s_syndrome#Cardiovas...
And Gilbert isn't "free" -- it comes at cost. The body is a machine, and engineering is full of tradeoffs.
People with high abilities in one area (geniuses) often have low abilities in others. Optimizing some protein for your heart isn't neutral for the rest of your body, etc.
The point about the stars is that evolution has "determined" that it can be optimal to take a ton of risks and die early than to live safely for 200 years (in some cases, of course evolution favors diversity too, which is why you see centenarians).
If you could get reward without risk, then it wouldn't work that way -- the "stars" would live forever creating great music and not drink themselves to death. But life is full of tradeoffs and reward involves risk.
Humans are highly social beings that naturally live in large kin groups. Knowledge and culture form a huge part of our survival strategy. Who among us have the most knowledge and experience to pass on? Elders.
Take a look at the role of elders in traditional hunter/gatherer cultures. Huge importance. Is it not implausible that natural selection would favour increased life expectancy so that elders can maintain and transmit the group's body of knowledge?
I'm more talking about people who want to raise life expectancy from 100 to 200, not go from 70 to 100 (not sure where the original article fell on this).
70 to 100 is clearly possible and we've already gotten a long way there in the 20th century (antibiotics, etc.) The "problem" now seems to be that not everyone actually cares if they live that long... i.e. there are plenty of people who don't want to live to 100, and might not even if they maintained the health of a 60 or 70 year old.
This sentence turn things into such an anthropomorphic way, to the point that the concept of evolution en engineering don't make sense anymore.
In the (scientific) evolution theories, evolution doesn't "engineer" life. It shapes life forms by environment constraints alone. And these constraints are in no appearing way optimized for fostering life, which appear more like an accidental byproduct. No conceptual framework nor any concern for conscious parsimony of implementation or sense of elegance are underlying evolution forces.
Indefinite youthfulness span would sure seems impressive. But it is nothing compared to other challenges that should be overcome to attain an exceptional life span: an unswerving immune system, not being killed by any domestic accident, human social violence or natural catastrophe, and not suicide yourself over psychological disorders.
There are scientific papers, BTW, which engineer solutions by evolutionary algorithms. Is that evolution or engineering? Clearly there's an engineering setup, made of all the constraints you speak about for the evolution process to take place, and that evolution process is also defined artificially, yet just like the real stuff, it follows a set of rules, so where's the divide? Why nature couldn't be engineering life with evolution, but humans could?
Your last point OTOH is quite relevant.
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.
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.
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.
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.
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.
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.
Evolution happens at all scales, not just the creature scale.
> But Katcher has no research grants or university lab or venture capital funding, no team of grad students mining databases and screening chemicals in the back room.
> One thing Katcher has going for him is the correct theory.
I start to suspect the author’s opinion is stronger than their evidence.
> In the race to effect substantial, system-wide rejuvenation, Harold Katcher is a dark horse. He has the right academic credentials and a solid history of research. In fact, in earlier life he was part of a team that discovered the breast cancer gene, brca1. I asked Harold for a biographical sketch, and have printed it in a box at the end of this posting.
And here's the bio sketch itself:
> So, you might consider me a late bloomer. While I have thousands of citations in the literature, with publications ranging from the discovery of the human ‘breast cancer gene’, to protein structure, bacteriology, biotechnology, bioinformatics, and biochemistry, there was no center or direction to my work as I had given up my personal goal of solving/curing aging when I learned that ‘wear and tear’ was the cause of it. Yet something happened in year 1985 when I was in California working with Michael Waterman and Temple Smith (fathers of bioinformatics) that is inexplicable: I found myself in Intensive Care with a tube inserted into my trachea and the knowledge that I might not live. And then I had a dream: I dreamed that somehow in the far future (and on another world), I was being feted for ‘bringing immortality to mankind’. Clearly, I survived that incident (started with an infected tooth). I lived a wonderful life – becoming a computer programmer (which I loved), leaving that for the University of Maryland’s Asian division, becoming a full professor and then the Academic Director for the Sciences, in Tokyo, Japan. By the time I left Japan in 2004, (my daughter Sasha was a fourth-grader, (yonensei), in the Japanese school system), I was teaching for U of M online – somewhat retired, and looking forwards to writing computer programs for fun and profit. Yet I never ever forgot that dream. It was clearly impossible; I had no lab – and really, there was no way to repair all damaged cells – it’d be like sweeping back the ocean. And then, in 2009, I read an old paper from 2005, a paper written by the Conboys, (Michael and Irina), Tom Rando and others, coming from Irv Weisman’s lab, that completely changed my life; that showed me that everything I believed about aging was wrong – that aging occurred at the organismic level, not at the cellular level and could be reversed. Well, the rest of the story is about persistence and the blessed intervention of Akshay Sanghvi who too saw there was another way and provided the structural, monetary, and emotional support (and some good ideas) that had me start a new career at age 72 in Mumbai, India. I feel twenty years younger than I did three years ago, I guess that’s another hint about aging. Now the ‘mystical’ dream? It wouldn’t be the first time in history that that happened – take that as a datum.
Let's consider the universe where Katcher has discovered the secret to aging. At some point in that universe, Katcher's work is going to be relatively unknown and unsponsored, and at a later point there will be trillions poured into it. The above quote you posted aligns just fine with the earlier part of that timeline so now you're just left to decide, given your priors about major scientific discoveries, how likely it is that a major scientific discovery can come from a "dark horse".
The vast vast majority of research discoveries happen within the system as part of large collaborations.
It's always healthy to have people going against the grain, but even they can find funding if they have ideas they can express coherently and that stand up to scrutiny.
Funding comes from calls from proposals which are within existing, established research fields. Funding outside of a current research field is nearly impossible to find. If your research isn't in an established field, there isn't an NSF/DARPA/etc. call to respond to, and there is no program officer who has any interest in your work.
Similar through the whole research pipeline. New areas of research don't have established venues where you can publish, people to cite your papers, or a community to write academic reference letters for you. People who work in new fields are usually doing so as nights and weekends projects, or are independently wealthy.
And although the vast majority of independent researchers are crackpots, a few are credible and do occasionally make major breakthroughs. Importantly, the majority of breakthroughs outside of established fields are made be people unsupported by NSF, and without good venues to publish (although quite often, those individuals are academics working in their spare time, so half within the system and half outside).
There are callouts in the article that try to calm down that viewpoint at least like: " Katcher thinks that the molecules involved will not be difficult to manufacture, so that when a product is eventually commercialized, it will not require extraction from the blood of live subjects, rodent or human. "
Perhaps for a good reason
2) The research in the blog post is not fully summarized. You know it's a weak blog post when they post results WITHOUT SAMPLE SIZE. This is a GLARING omission and highly unscientific. The actual paper shows n=593 rat tissues and n=850 human tissues, which is fine but the blog post should report on these details.
3) It's not that new to suggest that younger individuals' blood plasma might have a rejuvenating effect.
4) They look at certain tissue types, which wouldn't result in changes to all tissue types, like skin, hair, brain, etc.
5) This is very early stages, again, we need actual trials in humans, and then those trials probably need to be followed up for years and years, since aging is a long-run phenomenon. This is more like a cohort study where we enroll a huge number into a cohort of aging-treatments and controls who have some other placebo-treatment.
I know of one at least one company (Spring Discovery) that is following some of this work up to find some driver molecules that could have the same effect as parabiosis. If interested in the topic I’d look at the work from the labs mentioned in the article as well as Saul Villeda (former grad student of Wyss-Coray, full disclosure I know him socially) at UCSF.
TLDR: This article is a breathless take on active research, clearly the author is excited. There’s reason to keep investigating, but the conclusions in the article are stronger than what the research can say conclusively at the moment. Very early days.
This reminds me of plasma treatment for covid-19 which is actually proven. Perhaps someone will create a market for that.
Genes, good eating habits and healthy dose of exercise (rather low/medium effort that lasts long like gardening or foraging mushrooms in their case), coupled with obvious things like no addictions... and voila. They both had very good work ethics, on a level I can only envy (thanks to communists that didn't get them far professionally but that's another story and it didn't bother them).
Bad part is, all of their friends and colleagues are dead by now. They can only meet their kids' generation.
My mum says it gets weird when people your own age you know start dying in numbers but even weirder when people much younger start dying.
True but Hong Kong life expectancy for men is 81.3 years so one should still consider this evidence in favor of the man doing something that extends his lifespan. Doesn't need to be smoking-gun level but still: update your priors.
P(works|someone doing this is 91) > P(works). n is 1 here so the probability hasn't changed much at all.
Before you get too excited and wonder where you can buy these magic pills, remember that there are things you can do right now to improve both your longevity and your quality of life: 1) sleep properly 2) eat properly 3) exercise 4) reduce stress
That being said I think that the next 20-30 years are going to be really interesting in this space, and if we indeed have any sort of proven breakthrough this will force us to rethink how we think about our society and our mortality.
Experiments have show large increases in lifespan, across mammals.
I don't know if that's because I enjoy food and bodily activity too much to value a longer life without them or because I'm addicted to food. I've wondered.
What wouldn't you be willing to give up for a much longer life?
the best example I have in this bucket is sugar. If you depend on sugar you're basically a drug addict (i know, i know, but just because it's socially acceptable does not make it okay. there is research out there that show sugar is as bad as cocaine when it comes to how addictive it is and on the health effect).
if you could pick just one intervention you could do quitting sugar is what you want (maybe if you're smoking, quitting smoking, but after that sugar is the nastiest thing you can put into your system)
I understand how people can have fulfilling lives after losing the ability to do those things. Would I voluntarily give them up for a longer life? Probably not.
Not necessarily. There's some evidence that when you eat might matter more than what you eat (given essential nutrition):
>Increasing daily fasting times, without a reduction of calories and regardless of the type of diet consumed, resulted in overall improvements in health and survival in male mice [1]
[1] https://www.nih.gov/news-events/nih-research-matters/fasting...
Now if we would be 40-like in our 60s and so on, that's another story. But first thing that would probably change is retirement age.
If you enjoy bodily activity and experiences, why not try fasting too :)
also, you can reduce caloric intake all you want, if you eat crap and don't sleep properly you're still going to have a bad time
Permanently.
If not joking: Have you tried this? I lost 36% of my bodyweight by eating under TDEE. It requires huge amounts of effort to even hit 25% under TDEE consistently. A lot of that effort involves annoying your friends and family by not eating the way they do. We're social animals. It's hard. Plus when you get to a certain weight you will realize you have to regain muscle tissue, and the question of a bulk/cut cycle will come to mind. Goodbye 50% under TDEE.
see: https://en.wikipedia.org/wiki/Life_expectancy#Life_expectanc...
We'll get some sort of usable artificial intelligence (meaning robot slaves and autonomous rovers) at some point, but I think it's a mistake to underestimate human intelligence.
but if you have thousands or millions of years ahead I think artificial intelligence is going to become a thing. also we'll drop the artificial and call it what it is going to be: intelligence.
Everything is made of stardust - including the androids we'd construct. ...and while "complexity" is one word for our DNA - another more accurate term would be "complete fucking mess of code". It breaks frequently, is nearly impossible to model and predict, and can only be modified with agonizing inaccurate testing.
Your only reasonable argument here is that computing power isn't up to snuff. That's true - but that argument is rapidly dwindling.
That just tells me you didn't write it, but I guess I already suspected that.
See https://phys.org/news/2020-04-dna-life-bookjust-jumbled-ingr...
Also relevant XKCD https://xkcd.com/1605/
The second link is funny, but not an accurate comparison because when decompiled/deobfuscated, the google.com page resolves to well structured code. The human genome does not - there are interdependencies that have no logical purpose - pure happenstance.
...but that's not really my point anyway. My point is simply that it would be easier to build a better system from scratch. It might not be able to self-replicate from a single unit in the wild, but that no longer needs to be a requirement for us as a species.
I'm not even kidding. Almost every protein in the human body has multiple unrelated functions, just because evolution says "hey, this is here, let's use it for something new".
Every new human is an experiment in code chaos.
That is why the phrase "DNA is the blueprint of the cell" is terrible. In a blueprint, one can move a door 6" to the right without affecting the rest of the structure, add or remove a window, etc.
If you look at the methods section, here is what you get for a description of the magic plasma:
'We used a unique plasma fraction "Elixir" developed by Nugenics Research.'
This seems to run counter to the philosophy of reproducibility.
https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1....
So the SV execs with their fit young blood-bois were right all along?
I remember talking about recent news that a few of us had heard about promising "young blood rejuvenation" with a bunch of random hicks in the woods of central Maine in the spring of 2014.
A classic example of this is nasal steroids for seasonal allergies versus histamine blockers. Steroids will actually cause the genes that code for histamine/inflammatory proteins that are released by the cells to be downregulated. Whereas antihistamines bind to the histamine receptor at the penultimate step in the process. Steroids have a much stronger effect and are the current first line treatment for allergic rhinitis.
Wear and tear.
I worked outdoor physical labor through high school, and I have the moles and other skin issues related to excessive sun exposure. I also have several joints that were injured then that have caused problems my whole life. I lost much of my hearing to childhood illness before I was twelve (an misdiagnosed issue that would have been malpractice in today's environment) that I followed up with too much live music, operating heavy machinery, and shooting trap.
Wear and tear.
So maybe we can extend the healthy life of our organs, but that isn't going to magically make injuries go away.
And I am not suggesting that young people should ever listen to people in their sixties, I certainly never did, but if you can avoid damaging your skin, hearing, and joints while you are young, you will live to appreciate that.
Nevertheless, there are significant conflicts of interest going on, so confirmatory studies by independent bodies in animal models are required. Then there are the human studies. They obviously want to use the epigenetic clock as a surrogate endpoint in humans, so the trial can be completed in a short time frame. Not sure about that, this is a fairly complicated surrogate endpoint we are talking about. Some more relevant biomarkers of aging in humans which incorporate functional readouts would be required at the very least.
https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1....
Enammel reconstruction.
Batteries.
The three pillars of perpetual breakthroughs.
Both of these metrics are still improving too.
That said, breakthroughs that would be phenomenally beneficial and aren't prohibited by physics are worth throwing money at decade after decade due to the risk/reward ratio. It's like playing the lottery where the odds are a million to one against you, but he payout if you win is a billion times your ticket cost. You probably won't win but you would be stupid not to try.
>18 rats were divided into three groups. 6 young rats (30 weeks old), 6 old rats (109 weeks old) & 6 old rats (also 109 weeks old) treated with plasma fractions from the young rats.
>Plasma fraction treatment consists of two series of IV injections, four times on alternate days for 8 days. A 2nd series of injections were given 95 days later. In its entirety, the experiment lasted 155 days.
>Blood was drawn at regular intervals for analyses to monitor the impact and cognitive functions were assessed 4 times. DNA methylation profiles of several organs were generated and age was calculated using six epigenetic clocks.
>Using the final versions of their epigenetic clocks the reversal was: liver 75%, blood 66%, heart 57%, hypothalamus 19%. Average rejuvenation across four tissues was 54.2%.
Source some David Sinclair tweets (more in there) https://twitter.com/davidasinclair/status/125991292869585715...
The only way to actually make significant progress in an area this difficult is to constantly be looking for answers everywhere we can.
Seriously though, does putting Tom Hanks’ blood plasma into a young coronavirus nurse age them a little bit? Does the effect work in reverse?
(Just to explain the above Tom Hanks had Covid and gave plasma in a convalescent serum).
The hypothesis is that "clock molecules" in the bloodstream provide a global age-clock for about five other tissue-specific age-clocks in the body. Spoofing the global clock signal for a long enough period tricks the subsystem clocks into thinking they are younger than they really are, including the native global age-clock mechanism.
Completely replacing your own blood with a young person's blood, repeating if necessary, would also accomplish the same trick, more expensively.
The real question is whether old tissues can function like young tissues when tricked into trying.
The only way to actually cure aging would be to develop sophisticated enough outside mechanisms that would be able to intervene and replace these biological mechanisms as they fail. Macro level replacements won't cut it either. Replacing an organ might give you a few years here or there, but it doesn't address the issue that aging fundamentally happens at a molecular / atomic level.
Depending what you mean by "become young again," that's not true. See https://med.stanford.edu/news/all-news/2020/03/old-human-cel... The problem here is scaling this up beyond tissue cultures.
> I would caution you that while you're correct in that repair mechanisms do exist, it's important to remember that these mechanisms are themselves composed from the same components as the rest of your body, i.e. they too will age and begin to fail over time.
The process of nuclear reprogramming to induced pluripotent stem cells, which is the subject of your referenced paper, is something that I believe to be a great scientific breakthrough, but nevertheless fails to address the accumulated mutations that build up over time in your cells. All those mutations don't just magically disappear.
It's important to understand that renewed growth is synonymous with cancer. The older you are, the greater the risk you face as your fail safes and redundancies begin to fail from corruption due to accumulated mutation. It's often better to completely turn the thing off, which is exactly what your body does, after a certain point.
The older you get and the more you age, the more you should focus on preventing the development of cancer over anything else as that will likely have the greatest impact in determining your life expectancy, assuming you continue to stay active, eat properly, and get enough sleep.
It's actually multiplied! When you clone from a corrupted source, the resultant cells contain all the mutations the original one had along with any new errors introduced during the process of copying.
Granted I'm not completely sold on the supplements quite yet.
This article was jolly also https://www.bostonmagazine.com/health/2019/10/29/david-sincl...
- natural as well as stress-induced telomeres shortening
- oxidative molecular stress
- accumulative viral damage on body's DNA
- natural atrophy of thymus (thymic involution)
etc
I'm curious about the proposed mechanisms, if any.
https://www.haaretz.com/israel-news/.premium-holocaust-survi...
Since I spend a lot of money on this kind of stuff I figured I'd share. The use of platelet rich plasma (PRP) is rapidly growing in the beauty industry. My wife has had PRP used in various procedures that have indeed created a more youthful appearance (by like 10 years). Basically they can inject it anywhere through hundreds of tiny needles. Most often this is done to the face but you can even do this to the vagina (you'd be surprised how many women over 40 do this). That is, if you want hundreds of needles entering the labia and (horror of horrors) the clitorous too.
There's even a process for men where you can have PRP injected in your shaft and the results (I'm to terrified of needles in my dick to try it) are quite good (firmness, sensation, youthfullness) from what I hear.
The PRP procedures my wife has had, although expensive, have had impressive results.
I don't understand what the "rage" would come from, or why it's "pot". This is available today, and many people pay for it. The results speak for themselves. People who pay for this stuff don't make a habit of talking about it. I'm going to guess by your comment that you're not as beauty focused as some other people. For beauty focused individuals this is serious business. Ever wonder why your favorite actress over 50 "hasn't aged" past 35? It's not just plastic surgery or makeup. This is how many people make a living in industries where looking old is not rewarded.