Experimental drug reverses age-related memory and cognitive decline in mice | Hacker News Reader

Experimental drug reverses age-related memory and cognitive decline in mice

neurosciencenews.com

191 pointstartoran66 comments

This is a result on mice and as far as I know, attempts to reproduce similar findings in humans have failed. So there it is to be seen if in this case it will give similar results in humans. The mouse models that are being used, often genetically engineerd to have a certain deposition for cognitive decline, might not suffer from the same type of decline that we see in humans. The drug thus might simply be a treatment for the type of genetic disorder that the mouse model has and not have any effect of the decline see in humans.

True, though also my amateur understanding is that ageing-related illness is better modelled that’s e.g. cancer. This is because ageing is a natural thing in all species, whereas for specific diseases, indeed you genetically engineered “mice with cancer”, which behaves then very differently.

Could be wrong ofc!

> ageing is a natural thing in all species

Not all [1].

[1] https://en.m.wikipedia.org/wiki/Biological_immortality#Organ...

Words like "natural" can be tricky. Dying when struck by a bus is natural. That doesn't mean that busses are a natural feature of the world, or that you shouldn't look before crossing, or that an ER shouldn't make an effort to save the bus-stricken.

What do you make of the fact that connecting aged organs to young mice restores the organs? I think we should pursue drugs and treatments that improve function in aged populations, do you? Maybe ageing bodies just need to be occasionally cleaned out to restore healthy function.

Maybe it is "natural" to die, but unnecessary to suffer collapse along the way? Worst-case we have to compete in our careers and marathons with then healthy elderly and endure that same happy fate ourselves.

What I meant is, “cancer” mice are carefully bred / engineered to develop cancer. You can imagine their disease dynamics are very different from the normal population of mice who get cancer more rarely (and presumably are eaten first by something else).

Whereas aging, you just let the mice get old. They have “real”, “natural” old age, not an artificial one.

Age is not considered a disease because everyone does it. If we can learn to change things, such as reset the Horvath clock through epigenetic methylation hacks, or through other methods, then some day aging will be something that affects a minority of people and will be redefined as a disease.

Ha, I think I can read David Sinclair's words there! (not a bad thing at all IMHO)

@see https://en.wikipedia.org/wiki/Lifespan:_Why_We_Age_%E2%80%93...

I follow his work and Dr. Yamanaka's work very closely, along with several other scientists working in this area. They have made substantial progress and there are some promising side benefits that have come from their work, including nerve damage repair, which has massive potential.

I believe brain tumors and bone cancer are natural. Also being eaten alive by wolves is even more natural. The entire point of medicine is to get rid of nature’s influence on our vitality

Yes, but this is still progress. Baby steps add up to miles.

>I know, attempts to reproduce similar findings in humans have failed

Specifically with this drug? Source? Not snark; genuinely curious.

I followed research into medications for Alzheimer disease after my late wife was diagnosed with Early Onset Alzheimers Disease in 2006. Please have a look at the list of publications I have collected, including reports of promissing findings, most of which, to my knowledge, have not lead to any cure of the disease. https://www.iwriteiam.nl/AlzheimersDisease.html Search for 'mice'.

You're 100% right that no drugs have been recently approved by the FDA to help with Alzheimer's. But I think parent is right that they haven't tested ISRIB in people yet.

"Mice lie and monkeys exaggerate" is a well known truism in research.

"attempts to reproduce similar findings in humans have failed"

CPH treatment may be useful in dementias of medium level in quite old groups of patients, since 48% of the verum group displayed improvements in the memory functions against 28% of the placebo group.

https://pubmed.ncbi.nlm.nih.gov/2506844/

"The drug thus might simply be a treatment for the type of genetic disorder that the mouse model"

Got any experimental or observational evidence for this hypothesis?

Isn’t that cheating if the mice have to be engineered to display the experimental result? Like duh of course it’s going to work. News headline: engineered mouses exhibits characteristics it was engineered to exhibit also water is wet.

At this point, it seems the only ones reaching immortality are the mice.

I also recall seeing an article recently on mice on the ISS that get really strong from some genetic tweaks IIRC. It always seems we don't hear much about these "breakthroughs" after the mice results do the rounds through the news organizations.

That could also just mean I'm looking in the wrong places though.

You probably do, it's just that the lab test breakthroughs were 20 years ago and now it's just a treatment.

We already know how to make people strong using biotech: steroids.

Douglas Adams got it right. https://www.youtube.com/watch?v=y5xcvAoKojo

We should really give death row inmates the option to be in scientific trials that are dangerous. I guess this could be misused if judges funnel people into the system explicitly to be used in these trials but I think it would be worth it if we could somehow prevent the above scenario from happening?

This creates some pretty perverse incentives.

Which I have addressed.

Reminds me of an excellent SMBC-comic: https://www.smbc-comics.com/comic/2013-02-08

There is even a twitter account dedicated to this "in mice" omission: https://twitter.com/justsaysinmice?lang=en

My other favorite is the use of "too much"

Example from that account: "Too much fructose can cause liver damage -- in mice."

To quote Stephen Fry, "Of course too much is bad for you. Too much is exactly that quantity which is excessive! Too much water is bad for you."

Funnily enough, I used to drink too much water and sent myself into seizures at one point. The nurse ran in, in hysterics to pull the IV fluids out of my arm, when the diagnosis came through. My coaches had always told me to hydrate, and I worked out hard (at the time), but I wasn't replacing the salt =) Ah, the innocence (and ignorance) of youth.

I am not a biologist nor a MD but I have some formal training in biology and huge interest in neurodegenerative diseases like ALS or Alzheimer.

The eLife article seems to me to be well written [0]

[0] https://elifesciences.org/articles/62048

Add "in mice" to the title.

Only tangentially related, but: has anyone found a drug/supplement/etc which aids them in memory retention, cognition, alertness etc?

The only thing I've found effective is modafinil for alertness and some general mental sharpness. Especially after a night of poor sleep, the mental alertness it provides is a god-send.

Bacopa is the only supplement I've seen with a pretty strong track record of memory improvement.

It takes 4-8 weeks to kick in and the two most common side effects people complain about are stomach issues and lack of motivation.

Fascinating. I'll do some research; appreciate the input.

Salmon roe at 50g per dose thrice a week works nicely for me. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596017/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399499/. I take it in conjunction with a source of choline and uridine.

I also take 2g of magnesium l-threonate per day. As a stimulant I take phenylpiracetam at 100mg per dose on a per need basis. Semax and selank I take on occasion.

Ice baths have also been very helpful. I'll leave it at that; pm me for further info.

Huh, fascinating. Re: the salmon roe, do you take a supplement which contains the lysophosphatidylcholine, or do you just down the eggs?

Ice baths: that's for mental acuity, or overall physical health? I know it's used frequently in high-level sports for recuperation purposes.

I just down the eggs; I've even come to like the taste.

It's for the mental acuity, but I'm happy for any benefits I can get, such as a higher white blood cell count and more brown adipose tissue, the loss of which is associated with aging.

I've found Dihydrogen Monoxide quite effective. It generally works best after a good night's sleep though.

I chew a 2mg stick of nicotine gum occasionally which gets me a small but noticeable boost in alertness for an hour or so. Studies indicate it temporarily increases working memory as well. I don't consume any nicotine otherwise.

Nicotine is also protective against Parkinson's.

The only thing that got me out of a recent glut was infrequent nicotine vaping. I find it works better than the gum, which tends to give me too much no matter how fast I spit it out. I've tried all sorts of supplements and nootropics in my quest to regain what I lost when I got sleep apnea a couple years ago.

Strangely enough, one thing that I find is also helping is a balaclava. I'm standing here like an idiot with a balaclava on because I find it helps me stay focused. I got it a few days ago to use when hiking. I just happened to notice while trying it on that I felt a little calmer. I used it last night while working and finally managed to get some shit done.

I'm also using spaced repetition to try to remember things. No apps or programs yet, just manual note taking and repetition.

I actually decided to try vaping nicotine to test whether it indeed was a cognition enhancer, and here I am months later addicted like it's nobody's business. Turns out trying this with an addictive personality isn't the greatest idea – appreciate the suggestion though!

Also, the balaclava is interesting: I can imagine the benefit is almost similar to that people get from using a gravity blanket. The weight and "hugging" effect might be very comforting.

Really sorry to hear about the sleep apnea; that's an awful problem to deal with. Hope you're able to find a treatment which works for you.

I wonder if that balaclava thing is similar to why I sometimes like sitting here in my home office with my hoodie pulled up like a hollywood hacker.

The "nootropics" communities have been trying to find magic combinations for decades. Most of the compounds that provide results are variations of stimulants, such as modafinil. The cognitive boost is not without downsides, however. Modafinil is uniquely problematic because it was glorified as being a non-stimulant and free of side effects when it became popular. Some of this was driven by overseas vendors who made a lot of money shipping Modafinil into the United States without prescriptions.

Modafinil has a long half-life of 13-15 hours, which means that if you take a dose at 9AM, half of it is still in your bloodstream at midnight. This can have a negative effect on sleep quality the following night, which tends to prompt users to want to take yet another dose the following morning, and so on.

Modafinil is also notorious for reducing verbal fluency in some (though not all) users. There are also plenty of reports of abused and dependence online, though not to the same degree as other stimulants. From what I can gather, most people who use it regularly for non-prescription purposes eventually give up due to escalating tolerance.

Most other nootropics compounds follow similar stories: Initial glorification, widespread uptake, steady loss of momentum as people realize the compound is not without tradeoffs and downsides, and eventually being relegated to an every once-in-a-while tool for those who have it.

In some cases, the negative side effects of a substance are so subtle that people don't make the connection at first. For example, cholinergic supplements are frequently touted as memory enhancers and miracle supplements. Unfortunately, cholinergic supplements also have a tendency to induce or worsen depressive symptoms over time. The Nootropics communities are full of people complaining about unexplained depressive symptoms while taking various choline supplements that they hoped would improve their cognition or memory.

It's interesting to watch from the sidelines, but at this point I've decided that nothing beats good sleep, exercise, social exposure, and good diet. Caffeine is an okay band-aid on difficult days when used in moderation, but any attempts to use powerful compounds to override sleepiness seem doomed to backfire with rebound effects later.

Hmm ... This is an interesting comment. Without intending to debate with you on the topic (I'm not an expert on this), I can say that, so far, I have only a positive impression from the only nootropics substance that I have personal and quite lengthy - several decades - experience with: Nootropil aka Piracetam. I have started using it periodically back in high school - following advice of a very good doctor neurologist whom I and my family have known for years - to improve my memory, attention span, resilience to stress etc. I have never experienced any side effects (including sleep problems and depression). I have continued using it periodically while studying at university (usually, close to and/or during exams and other stressful times). That was in Europe several decades ago. After immigrating to US some 20 years ago, I have used Nootropil and Piracetam several times over the years (for several weeks at a time), but I had to resort to asking friends traveling from Europe to US to get it for me, since it is not yet widely available here (fortunately, people are allowed to import it for personal use, which was the case). I feel that I would significantly benefit now from taking Nootropil, as my mental sharpness, attention span and memory are not what they used to be (not to mention a lot of stress and sleepless nights that I have gone through over the recent years due to some extremely challenging family circumstances). I've been exploring some buying options (including relevant info on Reddit), but various things have distracted me from getting Nootropil and, hopefully, improving my shape and life. Of course, I realize the importance of "good sleep, exercise, social exposure, and good diet" and I'm doing my best in this regard, though, for various reasons, definitely not enough. In any case, there is always some room for improvement. Having said that, I believe that Nootropil can help me further enhance various aspects of my health and life to complement the positive effect of the above-mentioned best practices.

I agree that Nootropil has amazing effects on cognition. However, it stimulates erythropoiesis, and I’m not comfortable with that. That’s why I prefer modafinil.

I've never heard about - and experienced myself - such erythropoiesis stimulation side effect of Nootropil. Is it documented in multiple solid studies somewhere? I'm wondering about whether it might be a potential side effect of a very limited scope (i.e., affecting only a small subset of people).

I have never tried modafinil (or any other nootropics) - will read more about it. However, based on my very brief review, it appears to be much less safe than Nootropil along with a questionable effectiveness as a "cognitive enhancer". Plus, unlike Nootropil, it is considered a controlled substance in the United States.

>> Only tangentially related, but: has anyone found a drug/supplement/etc which aids them in memory retention, cognition, alertness etc?

For me it's a good night's sleep. I need 8 to 10 hours for best effects. Complemented by a 20-30 min. siesta after lunch, when possible, particularly in the summer. The feeling of being fresh and sharp in the morning is almost physical.

Same as you, the only safe one that has worked for me is modafinil. Piracetam also works, but only the pharmaceutical version by UCB Pharma. But I consider it unsafe, because it it stimulates erythropoiesis.

Naive question: mice don't live very long, humans live a long time. Does this imply that it _should_ be easy to extend a mouse's life, and for the same reason, very difficult to extend a human's?

Anyone know when they are allowed to start trying this in primates?

As I understand AD, no other primates get the same form of the disease that humans do. To wit, “Aged nonhuman primates with abundant plaques, however, do not manifest neurofibrillary tangles, nor do they become demented”.

https://www.alzforum.org/webinars/alzheimers-disease-uniquel...

Well that's pretty interesting, something about our evolution and increased brain capacity may be causing this to happen then.

Who is they? We should promote amateur science among those with the means, ability, and integrity.

That seems to me to be the best route to more drugs, cheaper drugs, and increased scientific literacy among the public. So much public reward and so little personal risk.

Sigma Aldritch has 25 mg for $400. Your hobbies could include a personal bio-science company. Wouldn't that be a more interesting future self?