A research group at the Max Planck Institute for Biology of Aging in Cologne, Germany, has now shown in laboratory animals that brief exposure to rapamycin has the same positive effects as lifelong treatment opening new doors for a potential application in humans.
Rapamycin, known for its positive effects on life and health span in experimental studies with laboratory animals. To obtain the maximum beneficial effects of the drug, it is often given lifelong.
The scientists have tested different time windows of short-term drug administration in fruit flies and found that a brief window of 2 weeks of rapamycin treatment in young, adult flies protected them against age-related pathology in the intestine and extended their lives. A corresponding short time window, 3 months of treatment starting at 3 months of age in young, adult mice, had similar beneficial effects on the health of the intestine when they were middle-aged.
Abstract
The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side effects from continuous dosing. Here we show that geroprotective effects of chronic rapamycin treatment can be obtained with a brief pulse of the drug in early adulthood in female Drosophila and mice. In Drosophila, a brief, early rapamycin treatment of adults extended lifespan and attenuated age-related decline in the intestine to the same degree as lifelong dosing. Lasting memory of earlier treatment was mediated by elevated autophagy in intestinal enterocytes, accompanied by increased levels of intestinal LManV and lysozyme. Brief elevation of autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, a 3-month, early treatment also induced a memory effect, with maintenance similar to chronic treatment, of lysozyme distribution, Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn.
The study is not without limitations. Aging phenotypes are often collected from very old mice (>18 months). However, aging phenotypes already appear in middle-aged mice39,40 and, indeed, evolutionary analysis indicates that aging is expected to commence with the onset of reproduction and adulthood41. In this study, we first assessed at what ages age-related gut phenotypes appear. Having found that they appear already at middle age (12 months old), we investigated the effects of short-term rapamycin treatment in early adulthood on middle-aged mice. Since these phenotypes are further exacerbated at older ages, it will be important to test in future the extent of protection that earlier-life, short-term rapamycin treatment confers in very old mice. Aging research is often limited by the need for long-term experiments, and the findings from our and other laboratories that age-related phenotypes appear and can be studied already at middle age, are of general utility for the field. Any importance of BCAT as a potential mediator of ‘rapamycin memory’ for gut dysplasia and lifespan in Drosophila should be assessed with a larger sample. A further challenge in this study was the measurement of autophagy in mice.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
Known for identifying cutting edge technologies, he is currently a Co-Founder of a startup and fundraiser for high potential early-stage companies. He is the Head of Research for Allocations for deep technology investments and an Angel Investor at Space Angels.
A frequent speaker at corporations, he has been a TEDx speaker, a Singularity University speaker and guest at numerous interviews for radio and podcasts. He is open to public speaking and advising engagements.
Rapamycin and drugs like rapamycin are out of Patton and too cheap for the major drug companies to produce. thus no use to their bottom line. Rapamycin drugs such as sirolimas modulate the immune system and have 25 years use to prevent kidney transplant patients from rejecting a donated kidney and are used on a daily basis – these patients hav a 2 % cancer rat vs the prior drugs rate of 5%. the colone Germany experiment is of enormous importance as poor autophagy leads to the diseases of old age and early death or poor health span. I am part of a 600 patient study at the u of Washington of side effects of rapamycin if used once a week. no serious side effects have been found so far. I am 87 and am starting my 5th year of 6mg SIROLIMAS (RAPAMYCIN)- AND HAVE+ effects on my cardiovascular system. M.
Blagosklonny in a paper in 2006 discovered that cellular(and the lifeforms) is programmed- thus can be slowed down with raoamycin. GBest MD
What about as an old man?
If you read the linked paper, they tried the obvious: What if you take it when you’re old?
Fruit flies: As the flies were dosed at older and older ages, the net improvement got smaller and smaller. Eventually it had very little effect.
Mice: They did one small batch of old mice, and it seemed to help a fair bit! But not as much as if they were dosed when young. Numbers weren’t enough to get solid data, or work out why the older mice didn’t do as well.
Has anyone else noticed that Rapamycin is a youth extending drug extracted from a lichin from a remote island which is EXACTLY the plot of the old John Wynham novel “Trouble with Lichen”? Except in his book, everyone got extremely excited by the news, rather than our own lack of interest.
Got excited for a moment, and was considering persuading my son to take it. Then I read “fruit flies”.
OK, mice too. Maybe I still will, but about 99% of things that extend lifespan in mice don’t work in humans. That’s always been the problem with testing anti-aging treatments in short lived lab animals: You get results fast, but we’re not a short lived species.
The shocking news that has not been yet revealed to the people is that humanity can get immortality now. Just build enough cryorefrigerators with solar panels in Nevada and there will be more than enough place to accommodate every human brain currently living or going to live in the next century. Less than 1 sq. meters of panels and 80 liters of cryovolume per person sum to 10×10 km square of some desert in Nevada for the annual number of the dead people from the entire Earth. Just use the right freezing procedure for brains that Kenneth Hayworth says about on his Twitter: glutaraldehyde perfusion and then ethylene glycol.
And there is no need to build those cryostorages for a whole century. The progress made by in nanoimprint lithography for the cheap production of flash memory, the progress made by in magnetic tape memory, etc. give us the opportunity to get a digitized human mind before the end of this century.
Anyway the electric power which is needed to keep those brains at -130°С is ridiculously small: something about 3 W per person. As my calculation shows:
https://docs.google.com/spreadsheets/d/1OGVRgsyds_YHD5Vfn7aj46kZDM9vl93o9fRAiTjs0us
So you get a cost of $ 1000 per person for a ten years storage. I.e. about $ 30 000 total for a chance to see year 2122:
– $ 5 000 an extraction,
– $ 10 000 a century long storage,
– $ 5 000 a scanning procedure,
– $ 5 000 a mind simulator and
– $ 5 000 for one chosen family who will manage all of that for groups of several thousand people joining annually.
Unfortunately we don’t have many companies similar to that. Who will contact Elon?
Yes, I’m familiar with the concept, I used to know Bob Ettinger, and was a member of Alcor for years, until I money got tight and I had to drop that to support my family.
It has always amazed me how little traction cryonics got with the general population. I think because almost everybody prefers to avoid thinking about the fact that they ARE eventually going to die. It’s somewhat easier to get people interested in fighting aging, because that’s only death adjacent, and even that didn’t get much traction until very recently.
I think that the problem with cryonics is that there is little point in freezing yourself for an indefinite amount of time if you cannot be assured that in the future aging will be so completely solved that you will be able to be thawed and *then* live a full life, rather than just *existing* in an unconscious state waiting for someone to solve your actual health problem, and not decide instead that it costs too much energy to keep random strangers from decaying and simply pull the plug on you (or they simply skimp on regular maintenance and you’re the poor devil whose refrigeration fails).
This goes times seven billion if you’re planning on freezing absolutely everybody. Who will be left to get actual immortality for everyone if the whole world is on the freezer? Who will make sure that the machines work into the far future?
“there is little point…” To me, if I do not freeze, I will have zero probability of life in the future. If I do freeze, the probability is greater than zero. A probability greater than zero is more than a “little point” to me.
Oh, damn… We had already discussed that. My fault 🙂
Cryofreezing everyone hoping that all diseases will be solved is one thing, but mind simulation is an actual scam.
I do have a twin brother (a natural clone), and I know this: my clone is not me, and a computer simulation of me is not me. Would you be able to implant the memories of my virtual self when I am eventually thawed so I will remember having “lived” that time? Very probably not. So what is the point of running a simulation of me, as opposed to some AI dedicated to simulated medical research?
Or if you can implant them, then you’re much better off implanting memories of learning useful skills instead (the old SF trope of instant automated learning). Simply pretend that everyone was getting a PHD in medicine, engineering and law while they were asleep, and start afresh when they are thawed. The thawing process has been perfected so far, hasn’t it? Several decades ago, the last I heard, it was rather hit-or-miss.
> Very probably not.
Why not? That is the point of a “scanning procedure”. Hypothetically they will cut a brain in many small pieces to allow many simultaneous work flows and then will scan each of those pieces by electronic microscope or something peeling at each scan a thin layer of molecules from the piece (the current techique for that is called “FIB-SEM”). Thus they will have the structure (connectome) of the brain and, if biological neuron models are developed well enough, they will be able to wake up a virtual copy of the person.
Kenneth Hayworth writes about all that stuff in more detail on his Twitter.
This is actually a popular topic of discussion among cryonicists; Repair the brain, or treat it as a high fidelity recording medium for the consciousness?
You can’t say that it’s just down to continuity of consciousness, because if that were the case, anybody who underwent deep anesthesia could be said to have died.
You can’t say that it’s continuity of structure, because the actual substance of the brain gets replaced over time, much of it, and it’s widely agreed that the Ship of Theseus is still the “same” ship, so long as they’re small parts, to the point where the ship could sail the whole while.
I think we look at this too simply. If at T1 you were subjected to some process that instantly duplicated you without any destructive analysis phase, at T2 there would be two beings that had equal claim to being the you of T1. Both of them would realistically fear death, but if one of them did die, the you of T1 would still be alive.
I think it’s a matter of causal connections: Post anesthesia you is causally connected to pre-anesthesia you, and so is a legitimate successor you. Likewise in the ship of Theseus. But T2a and T2b are not causally connected to each other, so neither is a successor state to the other, even if both are successor states to T1.
In the destructive analysis and simulation scenario, the simulation IS causally connected to the original you. So I think it really comes down to how good a simulation it is. Cell by cell? A chat bot that’s read your blog posts?
Hans Moravec combined simulation and Ship of Theseus in his Mind Children, in what I think was an effective way of thinking of these things.
We see questions like this in science fiction, too. In the popular Altered Carbon novels, and cable series, the people have chips in their necks that record their minds almost constantly.
They frequently upload their minds and download them to a different body, terminating the old one or releasing it to another upload. They mostly travel between stars by transmitting recordings of their minds to bodies around other stars, If they want to stay conscious enroute then they take up residence in a VR as bodiless simulations in extremely small starships (maybe the size of a can of soda).
If they actually need to go in an organic body, they do so by cryogenically preserving it. You and I might think that is preferable to becoming recordings, and copies of recordings as we seldom have a problem, mentally, with the idea of someone being frozen and thawing out and, because of this, never actually dying. But think about it.
With sufficient genetic modification it might be possible to make humans achieve a state of cryobiosis by other methods, such as drying themselves out completely, the way water bears (and most plant seeds) do. It’s called anhydrobiosis.
We accept frozen, but how about dessicated (just add water and a dried up mummy returns to life)??? It’s certainly biologically possible; we have examples. But it really shakes our understanding of just what death is and, therefore, what life is.
The elephant in the room in these kinds of stories is: What makes them so convinced that they aren’t simply dying and being replaced by copies? While some people might be okay with it, most of us would not be terribly blasé’ about casually dying and having a perfect copy inherit all our stuff.
Unless, and here is the big one, the branching world-lines of your consciousness, your state of awareness, are never really severed and can even remerge, when they become indistinguishable from each other. But that presupposes certain advances in cosmology that may not be attainable, conforming to a specific hypothesis, that may or may not be correct, or provable.
> What makes them so convinced that they aren’t simply dying and being replaced by copies?
What makes us convinced that falling asleep and waking up isn’t simply dying and being replaced by copies (from a continuity of consciousness point-of-view, at least)? From the consciousness point-of-view, it’s not too different to hybernating your PC, and then reloading on the next boot. For the PC, the data is the same, but it’s a new copy. Is it not the same for our consciousness?
The answer is the repeated experience of the person at the other end. The “us” in the morning has went to sleep and woken up so many times, and every time it felt like the same “us” as the evening before. So we grow to believe the same will be the next night. And the night after that. And after that.
By the same token, someone who underwent many mind uploads and copies, and every time, in retrospect, it feels like it’s still them – they’d be a lot less apprehensive than someone who has never gone to sleep yet.
“What makes us convinced that falling asleep and waking up isn’t simply dying and being replaced by copies ”
Would explain how some people treat their marriage oaths “till death do us part”
If you want to take this further, we’re currently biased by our daily experience since the day we were born, that there can only be one “me” running around. But if mind copying was possible, then there could be more than one. More so if you could sync back the experiences from each of the copies, and between them. Why must we be limited to a single body, a single brain, and a single copy of consciousness?
Your copies would have the same personality, the same responses, the same motivations. They’d be extensions of you, acting on your behalf in the same way you would. Yes, the longer you spend exposed to divergent stimuli, the more you will diverge. At some point, it may be fair to call them “not me anymore”. But if experiences are re-synced every so often (or even continuously), then parity is restored.
As for the twin argument presented by Wtrmute, the twin’s brain developed separately, grew separately, experienced separately. They were divergent from the very start, never a true copy.
If thinking along those lines, we can learn to accept copies of us separated by space, and think of them as “still us”, then why not copies separated by time? They will diverge, sure, but no different than the “you” of today have diverged from the “you” of a decade ago. Surely, many of us have looked back at ourselves some many years ago, and realized we’re not quite the same person anymore.
I think the relatively low cost of cryonic freezing is what makes it perfect for people that are so mentally twisted that they can never be returned to society. Someday it may be possible to cure whatever turned a person into a serial killer, or whatever, but that day is not this day. While the medical profession grows increasingly capable of making accurate diagnoses, there are few cures, only treatments, and those aren’t terribly efficacious.
The humane thing would be to cryonically freeze them until such time as anyone with severe enough mental problems such that they lead to behavior that gets them sentenced to execution, or life imprisonment without parole, can be cured, not just treated, but cured.
It might also have a chilling effect on the cost of the criminal justice system as it would have the added bonus of being far less expensive than state-mandated executions, or maintaining people in prison for the remainder of their lives.
There have been limited trials on humans. Dr Brad Stanfield, youtube channel with same name, is trying to raise money to fund a large doubleblind study on rapamycin but is having little success in raising fund. For some mysterious reason Big Pharma is not showing much interest in studying the benefits of an off-patent drug.