Drug Reverses Age-Related Mental Decline Within Days (ucsf.edu) 98
The University of California San Francisco issued this glowing announcement of some new research:
Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, according to a new study by UC San Francisco scientists. The drug, called ISRIB, has already been shown in laboratory studies to restore memory function months after traumatic brain injury, reverse cognitive impairments in Down Syndrome, prevent noise-related hearing loss, fight certain types of prostate cancer, and even enhance cognition in healthy animals.
In the new study, published Dec. 1, 2020, in the open-access journal eLife, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.
"ISRIB's extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological "blockage" rather than more permanent degradation," said Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science.
"The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress," added Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. "Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time...."
"We've seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline," said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. "It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step."
Forbes also reports that "In all studies, the researchers have observed no serious side effects."
In the new study, published Dec. 1, 2020, in the open-access journal eLife, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function.
"ISRIB's extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological "blockage" rather than more permanent degradation," said Susanna Rosi, PhD, Lewis and Ruth Cozen Chair II and professor in the departments of Neurological Surgery and of Physical Therapy and Rehabilitation Science.
"The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress," added Peter Walter, PhD, a professor in the UCSF Department of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator. "Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time...."
"We've seen how ISRIB restores cognition in animals with traumatic brain injury, which in many ways is like a sped-up version of age-related cognitive decline," said Rosi, who is director of neurocognitive research in the UCSF Brain and Spinal Injury Center and a member of the UCSF Weill Institute for Neurosciences. "It may seem like a crazy idea, but asking whether the drug could reverse symptoms of aging itself was just a logical next step."
Forbes also reports that "In all studies, the researchers have observed no serious side effects."
I Will Take Two (Score:3)
Hope I can remember to take it.
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Come on, rodent up! What are you, a man or a mouse? I bet you wish you were a mouse *now*, you primate!
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This is not a reputable research article. It's more like an ad for a miracle cure. How do I know? The article does not identify the small molecular weight component that has these wonderful properties. That guarantees that no other lab can repeat the studies. I suggest ignoring this article.
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I believe this "ISRIB" drug is proprietary.
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Doesn't matter how proprietary it is. The GP is correct: it ain't a scientific publication unless you provide enough information for someone else to repeat the experiment.
The way you do this kind of thing is you patent the drug, release complete details, *then* write the paper. Filing for a provisional patent costs $25 and takes about ten minutes on the interweb.
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The GP is correct: it ain't a scientific publication unless you provide enough information for someone else to repeat the experiment.
Indeed. It is a press release, not a scientific paper. Unfortunately, all its references are to other press releases. The focus is on marketing, not science.
The personal page for Dr. Rossi has this publication listed: Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury [nih.gov].
There is also a Wikipedia page for ISRIB [wikipedia.org]
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It looks like ISRIB might be a pretty decent drug for improving memory function. Most of the other claims are a bit iffy.
Mice don't get Down Syndrome. But if you mess up their genes in an analogous way, ISRIB seems to cause them to engage in normal behaviours, like exploring their environment, more frequently. That's consistent with improving their memory, but "reversing" the syndrome is going too far.
Mice lacking a certain gene experience hair cell and hearing loss when exposed to normal sounds. Giving the
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The GP is correct: it ain't a scientific publication unless you provide enough information for someone else to repeat the experiment.
Just like we do with all other medicines, like the new Corona vaccines? Har har har.
If you want to repeat the experiments: simply order the drug from them. (* facepalm *)
No idea if you can patent a drug without prove it is working and without mentioning its structural formula.
Re:I Will Take Two (Score:5, Informative)
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I think they call it freedom. What little of it is left.
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Shut up and take my money
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You can buy all sorts of chemicals that if you ingest will have all sorts of undesirable outcomes, people can get high snorting petrol fumes. You can buy all sorts of complex chemicals which are not regulated until they need to be regulated due to abuse. What you want a licence to go to the bottle shop to buy a bottle of beer, one at a time because safe dose and you must be licensed to prove you can use it safely and without a licence you can not buy it else you might drink yourself to death or operate a mo
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I'm frankly surprised it has not been.
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I'm less concerned about the price and more about the fact you can just straight up by experimental medical drugs that easy.
In many countries around the world, medicine is far more accessible than in America. Yet the sky hasn't fallen and the world continues to turn.
Perhaps using the medical establishment as an extremely expensive gateway to accessible medicine isn't as critically important as you have been told.
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Uh, side effects? Allergic reactions?
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The main problem is that chemical grade ISRIB is not necessarily medical grade.
While the chemical purity might be pretty high as a percentage, toxic (unless it's also food grade) or infectious agents might be present.
Infectious agents in particular are hard to eliminate, a few years back hospitals were running out of medical grade baking soda. While they could run down to the corner store, they risked giving their patents horrifying infections from the way they were using the baking soda, unless it was comp
Re:I Will Take Two (Score:5, Informative)
Typical logical fallacy. (Score:3)
Uuum, there are countless things that are not as simple as a single molecule. Yet we trust in them all day every day.
It is false to extrapolate from that, that we cannot replicate it *AT ALL*.
Certainly, the method can be replicated. And if the effects then cannot, then clearly the study was bad. And if it can, it was good. Because that's what peer review is. Unlike your single thing you did latch onto.
Now imagine if it was good, and nobody decided to repeat the experiment, and it got lost and forgotten, onl
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I think I've seen a movie about this... (Score:1)
Re: I think I've seen a movie about this... (Score:4, Insightful)
Re: I think I've seen a movie about this... (Score:2)
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Frequently. Mouse brains aren't really very much like ours.
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I beg to differ with you. I have met many mouse brained fools.
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Don't mistake similarities in behaviour for similarities in structure and biochemistry. There are many roads to foolishness, and observing the fool is often not sufficient to determine which one they took.
Rush order (Score:2, Funny)
1600 Pennsylvania Ave NW, Washington, DC.
Please schedule delivery for January 20, 2021 or as soon as practical thereafter.
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If only he could remember to take it. But it's easy to tell when he's forgotten his meds. He runs around calling people Dog faced pony soldiers.
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But what if they ARE dog-faced pony soldiers?!?
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1600 Pennsylvania Ave NW, Washington, DC.
Please schedule delivery for January 20, 2021 or as soon as practical thereafter.
Why bother? By that day, it will be too late.
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Pretty much. And President Trump didn't always do that. Look at his speeches from the 1980s, and look at his speeches recently. That's not a small amount of cognitive decline. It's Yuge. Not trolling here. The difference is dramatic.
If he had been at his mental best for the last year, I think the coronavirus death toll would have been a whole lot lower. But I don't blame President Trump for those deaths. Rather, I blame every single senator who refused to do his or her constitutional duty to find h
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I'm in no way defending Trump here, but if you think Joe hasn't gotten much worse over the last few years, you haven't been paying attention. Castro even dinged him on it during the Dem debates "Are you forgetting what you said two minutes ago?". He is on video saying he's a candidate for US Senate, instead of President...really??? Sorry no, Joe isn't all there anymore, and he'll be gone before his four years are up.
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ISRIB vs. McRib (Score:1)
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The United States Food and Drug Administration has not evaluated the statements made in this advertisement about MCRIB.
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I'm sorry, but ISrib is not available to infidels. ;)
Don't worry (Score:2)
You can't afford it.
Think carefully before you take this. (Score:1, Insightful)
Re: Think carefully before you take this. (Score:3)
You can take something else for that.
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Some people swear by intoxicating drugs.
great news (Score:5, Funny)
Great news for aged mice!
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I know. The amazing things we can do for mice at this point are mind blowing. We can extend their lifespans by more than double, make them ripped and have no need of exercise to get all the benefits, and now improve their cognitive ability. Who knows what else that I'm not familiar with.
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(For those of you that remember SNL when it was funny.)
Flowers for Algernon (Score:5, Informative)
I read that story, it was pretty good.
The Molecule In Question (Score:5, Informative)
ISRIB is trans-N,N-(Cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide, [sigmaaldrich.com] a small molecule discovered (in this application) by semi-automatic screening of a large library of small molecules. So someone had to have bothered to make it for some prior reason.
Re:The Molecule In Question (Score:5, Informative)
... a small molecule discovered (in this application) by semi-automatic screening of a large library of small molecules. So someone had to have bothered to make it for some prior reason.
Not necessarily. Other computational chemistry programs can enumerate the possible small compounds with various combinations of atoms and bonds and compute the stability and properties. Doing it from scratch is one possible (though large) approach that would include new molecules, filling in the blanks in existing tables of known molecules is another.
(Having said that, I must admit that I have no idea whether the library this group used is one of known-to-exist molecules with known syntheses or if it includes other possible molecules and, if so, how they came to be included.)
One reason the computational drug chemists search small molecules for useful drug activity is that many small molecules can make it through cell membranes to do things in the cell, while most large molecules can't, so their effects are limited to the cell surface and environment. But another reason is that computational requirements blow up quickly as the molecules get larger. So a given amount of crunch farm can process a LOT of small molecules or far fewer large ones.
Fortunately there are a LOT of possibe small molecules and they have very diverse properties.
There's nothing worse than ... (Score:2)
... people who believe something that great can never happen and blindly dismiss it outright.
That's what I think.
But even I would like to see some peer review on this.
Not just an open access journal and a glowing review by a uni.
I'd like to be that peer, please. ;)
Lucky! (Score:5, Funny)
Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice,
Those mice are lucky bastards because scientists make all the cool new drugs for them. It's like an obsession, always making breakthrough for mice. I'm beginning to think that scientists are trying to supermice soldiers that are going to replace us all. Why scientists, why can't you make some cool stuff for humans? ;)
Re:Lucky! (not) (Score:3)
The mice were not lucky in the end.... "All mice were lethally overdosed using a mixture of ketamine (10 mg/ml) and xylaxine (1 mg/ml). Once animals were completely anesthetized, blood was extracted by cardiac puncture and animals were perfused with 1X phosphate buffer solution..." So none will make it to the rank of supermouse.
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Re:Lucky! (not) (Score:4, Interesting)
Probably preparation for dissection - you don't want any trauma or blood obscuring any details while you examine the drug's pysiological impacts.
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Is that really how lab nice are disposed of? Seems a little elaborate.
No, they juse use the Polytron [zork.net]. It reduces an entire mouse to a soup-like homogenate in 30 seconds!
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They can't take over the world? LOL
Pinky and the Brain brain brain brain.... Narf.
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Damn mice get all the breaks! New experimental drugs, genetic modifications, cyborg implants... all at no charge!
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Well, no charge aside from a wee slice of their neck... (metaphorically speaking)
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Slashdotters usually downplay these kind of storie (Score:5, Informative)
Slashdotters usually downplay these kind of stories, but it is at least possible that a huge breakthrough has been made.
ISRIB has been licensed to Calico, which is owned by Alphabet - better known as Google.
Calico LLC is an American research and development biotech company founded on September 18, 2013 by Bill Maris and backed by Google with the goal of combating aging and associated diseases. In Google's 2013 Founders Letter, Larry Page described Calico as a company focused on "health, well-being, and longevity". The company's name is an acronym for "California Life Company".
https://en.wikipedia.org/wiki/... [wikipedia.org]
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Slashdotters usually downplay these kind of stories, but it is at least possible that a huge breakthrough has been made.
Possibly. But we better check some things out first. Let's hope it isn't like those Alzheimer's drugs that just make the dying process all that much longer. Instead of spending the last 2 years of your life brainless, you can spend 5 or 6 years brainless. The nursing homes love it though
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I was under the impression that existing Alzheimer's drugs were ineffective. I don't think that they significantly increase people's lifespan:
https://www.ncbi.nlm.nih.gov/p... [nih.gov]
ISRIB was initially seen as a drug to treat traumatic brain injury, but further studies have widened the potential scope of the drug. In all likelihood, the potential seen in the mice study won't transfer across to humans - but it would be a game-changer if it did.
No retiring at 65 (Score:2)
With this drug you can keep 'em in the cubicles 'till 80+!
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They also have a 50/50 collaboration with AbbVie where they do the early stage stuff, Abbvie does the late stage work, and they split the cost and profits 50/50. So it looks like the two investment points for those interested might be AbbVie and Alphabet.
After reading the various research announcements, it does appear to me that this could be really huge. I see no indications of how much it costs to make, but it wouldn't matter much. My guess is that this would be something that everyone in the world over t
Re:Slashdotters usually downplay these kind of sto (Score:5, Informative)
It could be a breakthrough but the possible side effects must be determined first. From one of the linked articles:
ISRIB, discovered in 2013 in Walter’s lab, works by rebooting cells' protein production machinery after it gets throttled by one of these stress responses – a cellular quality control mechanism called the integrated stress response (ISR; ISRIB stands for ISR InhiBitor).
The ISR normally detects problems with protein production in a cell — a potential sign of viral infection or cancer-promoting gene mutations — and responds by putting the brakes on cell’s protein-synthesis machinery. This safety mechanism is critical for weeding out misbehaving cells, but if stuck in the on position in a tissue like the brain, it can lead to serious problems, as cells lose the ability to perform their normal activities, Walter and colleagues have found.
In particular, recent animal studies by Walter and Rosi, made possible by early philanthropic support from The Rogers Family Foundation, have implicated chronic ISR activation in the persistent cognitive and behavioral deficits seen in patients after TBI, by showing that, in mice, brief ISRIB treatment can reboot the ISR and restore normal brain function almost overnight.
So, the ISR plays a critical role for infections and cancer. If it is just a single use "reboot" of a system that somehow got stuck it could be great (just like how rebooting your Win95 made the machine feel new and fresh). The indication in the article is that it could be just a reboot.
But if you have to take the drug continuously it might inhibit otherwise important reactions to viruses and cancer. This complicates the cost/benefit analysis a lot. For example, cancer is rare and if you want to compare the cancer rate between a control group and an intervention group, you need a very large/long term study to accurately assess risks. If the trade-off is better cognitive performance vs increased cancer risk, you really need good data on both benefits and risks before making any decisions. I'm not sure if a doctor could recommend a drug with that trade off even if the patient might willingly take the risk.
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Old secret medicine (Score:2)
When my granddad got a beer, his mental decline disappeared within seconds.
Re: Old secret medicine (Score:3)
You think your making a joke, but Beer is actually the best food source of Uridine. Uridine Monophosphate is sold as a memory enhancing brain supplement. It makes sense, because I know a 90 year old who drinks âoeone and only oneâ beer every day, and has the best memory of anyone else that I know at that age.
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Yeah, and I know people who smoked until they were 100. Doesn't mean they weren't damaging themselves. Anecdotal evidence = not evidence.
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Anecdotal evidence = not evidence
Or course they are evidence. Everything that happens and is observed is evidence, every other attitude towards it is retarded.
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Yes, I had a poor choice of words. However...
https://www.scientificamerican... [scientificamerican.com]
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The article ha not to do anything with it :D
Point is: many americans use stereotype phrases like "anecdotes are not evidence" or "in this house we obey the laws of thermodynamics" - without knowing anything about it.
And drawing absurd conclusions from it.
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The point is that anecdotal evidence is next to useless. It's like my friend who only survived a collision because he was not wearing his seat belt. Drawing a conclusion from that is pointless.
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No it is not. Why would it?
It is the same evidence as any other evidence.
What about your friend who died in a car crash but was belted? Hu?
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It wasn't a joke. If anything should the joke be that beer has the reverse effect on young people.
However alcohol is associated by many with a joyous experience. And when an old man, who really shouldn't be drinking much of it at all, is given one occasionally, then it brings back joy but also memories and happiness. It doesn't last forever, but it sure is wonderful to see an old man light up again.
Good (Score:1)
Hope the results are permanent and have no side-effects. It's about time we start working on curing another pandemic: aging.
Yea, And (Score:1)
Sounds a bit too good to be true (Score:2)
That very likely means it is.
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Re:Sounds way too good to be true (Score:2)
Checking... (Score:2)
I, for one (Score:2)
This can't possibly come quickly enough (Score:2)
My father, who just turned 90, has been experiencing a steady mental decline for much of the past year. It's been tragic witnessing the enormous change that has come over him in this time, not always understanding what is being said to him, despite apparently hearing it. Thankfully, there have been no cases of COVID19 in the care home where my parents currently live.
But honestly, I don't know if he will still be around next Christmas if this continues.
If I may be frank, I am a little sick and tired
If real, you can rest assured. (Score:2)
This will be priced well out of the hands of common people.
And I know how it will be named: "Inaprovaline" (Score:2)
https://memory-alpha.fandom.co... [fandom.com]
Really great news (Score:1)
This is really great news! ...for mice.
... in mice (Score:3)
https://twitter.com/justsaysin... [twitter.com]
nuff said.
2 please (Score:2)
I need a combo-shot of this stuff and the vaccine.