> Researchers using mouse models found that altering the CaMKII brain protein caused similar cognitive effects as those that happen through normal aging.
This should be the title of the article. Honestly these supposedly dissemination articles do not offer much more than reading the abstract or skimming a bit through the article itself.
Realistically, with the title you suggest nobody would have read the post.
A title is not "the most informative and complete sentence summarizing the article", it also has the goal to stimulate curiosity. I understand that we don't want misleading titles but this obsession on titles is not very helpful. I am participating in this useless conversation but I couldn't help myself. Now every single HN post has a comment on how the title is wrong..
>A title is not "the most informative and complete sentence summarizing the article", it also has the goal to stimulate curiosity.
It shouldn't have to do the latter. That's clickbait. People are either organically curious about what actually happened or they are not. If they are not, they shouldn't be "stimulated" with BS. That "media/advetising" attitude is the cause behind many issues with science in society today.
Ehh. We’ve been here long enough to both know that there’s a balance. $10 says the mods won’t change the title to the suggested one, precisely because of this balance.
It’s not about clickbaiting. The whole reason the research is getting funded in the first place is to try to find the link.
Grants are ALWAYS tiered based on biased political factors. That's why they are "grants". Someone heavily invested in finding answers is willing to give money away to achieve that end. In this case, the government is heavily invested on ideas that can stimulate their economy.
I don't even know what can be done here. Take money out of acedemia? Maybe in a post scarcity world.
The Artifact news reader app on iOS uses this premise to provide one of the truly useful implementations of LLMs I've seen in the wild so far. You can mark a title as clickbait, and the app will use AI to generate a new title, usually one that is more usefully descriptive.
It's not perfect, sometimes the generated title is still totally clickbait and I've seen a couple instances of it being completely wrong or hallucinating a detail. But generally it's pretty neat.
The app also uses the same tech to summarize articles into a few bullets which I don't use as often but is also neat.
>It shouldn't have to do the latter. That's clickbait.
clickbait generally has an implication of incorrectly representing the content. romanticized titles aren't always clickbait, and I wouldn't say this is exactly a sensationalist tite like how others may say "We're on the first road to curing Alzheimer's disease".
>People are either organically curious about what actually happened or they are not.
it's a prisoner's dilemma. It's not necessarily zero sum, but attention is somewhat finite. And for some sites, the result isn't a more comfy high quality community. It just dies out, and that benefits no one.
Why did you italicize a word? Why speak with any emotion ever? Why not focus exclusively on the optimal method of transferring information from one being to another?
In this case, I believe that using italics to convey emphasis and a bit of emotion is the optimal method of transferring information (here, expressing surprise and questioning someone apparently favoring a practice that is generally correctly viewed as a pure negative).
The title of the study is "Decreased nitrosylation of CaMKII causes aging-associated impairments in memory and synaptic plasticity in mice" - that would have been the base of the shortened title, if the study had been submitted.
The dissemination article was chosen for submission because it was the one from the source University. (There are more around.)
Further from using clear, synthetic expressions, it contains more information than just the (available abstract of the) research article - it is where an author of the latter states that next steps are pharmacological and involving humans.
>Please don't complain about tangential annoyances—e.g. article or website formats, name collisions, or back-button breakage. They're too common to be interesting.
You're complaining that the title of TFA is not what you expect. This is certainly a tangential annoyance, and certainly not an interesting comment on the article. If you don't like the submission just flag it and move on. Do better.
Agreed. This press release is over-the-top and implies that THE one major cause for neurocognitive decline with aging has just been discovered. I doubt the article is quite so hyperbolic. The temperature of press releases for research papers in aging and dementia research needs to be cooler.
I've noticed a cognitive decline in myself the past couple years. I'm in my mid 30's though so I assume it's more related to long covid. One of the biggest side effects of long covid for me was horrible insomnia, which was killer. The insomnia is mostly gone, but I'm still not my previous cognitive self. It's terrifying to be honest.
I had the same after COVID. Took me many months to start feeling functional again. Any time I tried to think about something, it'd just... noise out? First 2-3 months were just awful
I went to a neurologist who said there's tons of people coming in with the same complaint after COVID, and since there's no literature on that yet, he couldn't really do anything.
I would like to point to this kind of statement that doctors often make, that there is “no literature” or that “nothing is known”. This is very often flat out wrong. Consider the size of the statement: Nothing is known and there exists no literature. The domain of knowledge required for the statement is omniscience. Having read all papers. It’s not an acceptable statement for anyone to make.
your earliest link here was August of last year. I have heard people taking about long COVID as early as early 2021. Properly researched literature takes time to be written and much longer to be peer reviewed and disseminated into the circle of the academic conscious.
I don't think there's much value taking the word that literally. I simply assume the acedemic conscious when I hear "there is no literature on X". I certainly wouldn't want a neurologist to tell me "oh yea I read some news on this last week and X" and treat that as gospel for an ongoing issue.
Yes, the earliest publication of those three is from almost a year ago. Random sample of papers. There exist studies / results / observations with actionable information older than that. (There’s probably something in the references sections of those papers, for instance.)
I of course accept the fact that information takes time to propagate, but the fact remains that I have been to specialist doctors for serious issues which have stated flat out that “nothing is known” – where they literally meant ”nothing is known”, which was completely contradicted by papers. Ten year old papers. Twenty year old papers. Fifty year old papers.
Again and again.
Certainly not all doctors are part of this culture. More than one time I have been present when a doctor who reads academic papers makes a decision based on that information which effectively saved a life.
Nonetheless, this hazard is a very real part of medical practicioner culture.
I certainly wouldn’t want a neurologist to treat last week’s news as gospel either. Absolutely not.
I just don’t know yet how to tell people how big this gulf can be between existing knowledge – established, proven, actionable knowledge – and what a given doctor acknowledges and/or doesn’t flat out deny the existence of.
Maybe this:
Anyone can read academic papers. In biology and medicine. Anyone. Really. And it is the minority of doctors who actually do so. I suggest that people verify doctors’ statements about the complete non-existence of knowledge about any given thing, should they make such statements. Read. Read as if lives were at stake.
—
Part of the reason doctors don’t read is that they are often overworked. They really, really are. (It’s not the only reason though.)
And: Of course!, reading science papers online IS NOT a substitute for medical training.
What I suggest people do is this: Help your doctors to help you.
With the utmost humility. As if lives were at stake.
I remember sitting trying to solve a problem to do with parent/child codes and modifiers, and I'd never had nothing come out, that was absolutely scary. 8 months later and I looked at it again and solved it so easily.
The big problem was that I'd always been able to hide my adhd symptoms, or at least 'clever' my way around them, and long covid / covid brain just laid them all bare.
Over 3 years after my first covid infection - still can't really taste or smell - I'm medicated for adhd, and I feel almost like how I was in March 2020.
I wonder how many people just fell into alcohol, isolation induced depression, sedentary lifestyle, weight gain, etc... and that their health decline had nothing to do with COVID.
When the pandemic hit I went the opposite. Focused on a healthy mind and body, was able to study a bunch and finally broken through a few mental plateaus.
But then I _got_ COVID and I can tell you COVID brain is real. Even after I had recovered physically there were a few weeks of obvious cognitive degradation. One of my first days testing negative I was trying to implement some pretty basic pagination logic but when it came time to writing the algos for it, it was like my body flipped a switch and I would get impossibly drowsy and have to go lie down.
I've had covid twice since then without the same problem but it is very real and wild.
Please forgive me for turning your words back on you: The issue with these statements such as yours is that they assume the non-existence of evidence that confirms that people’s experience is real.
there wasn't really much of a lockdown where I live, so I sincerely doubt that. Also I got COVID after the entire lockdown was over everywhere (2021), sooo no
After my startup failed and I broke up with my girlfriend, my cognition massively changed: I was less creative, less quick, and I could see it reduce my ability to code. Otherwise, I lost libido, had paranoia in social interaction, and alcohol or marijuana would cause me paranoia. When I would ride my motorcycle on curvy roads, or when I would play a racing game or read a book, I couldn't get into a flow anymore. Thinking about activities would stress me to the point that I would avoid doing anything.
After a number of years I feel normal, and I think it was due primarily to finding and sticking to a routine. The routine involves little things like watering plants and making coffee, and I just do them every day without thinking. Otherwise it includes exercise, sleep, chores, work, and procrastination.
I had to finish up my PhD while already working at a FAANG. My professor would keep stacking more stuff that he wanted to have in my thesis. It was a horrible time and I think I was very close to a burnout.
One thing that I later noticed was that I e.g. couldn't enjoy any music anymore. I always used to be able to be absolutely amazed by some tracks and dance to it at home - but during that time there was just nothing.
I recently quit my dev job because it was too stressful and I was burning out. I seemed to almost instantly get better at thrashing my motorbike in the twisties... I'm not sure why exactly but it feels like a weight was lifted and it just allowed me to focus and enjoy being in the moment a bit more.
Yeah, I found too I wasn't eating enough. I estimates I was eating around 1500-2000 calories regularly and I never really felt hungry. Once I started forcing myself to eat larger meals I felt a lot better and started feeling hunger again.
fyi, this can happen in a successful startup/business also. this happened to me when i was stressed out of my mind and stuck doing work i hate for customers i didn't want after 10 years of running a biz.
it took a breakup, a sale of the business, and nearly 2 years of doing nothing until i recovered.
fwiw, the biggest takeaways the whole thing taught me are 1. be careful of what you wish for and 2. both attractive women and customers want outcomes, they don't give a shit about your problems and 3. never forego vacations/holidays for work.
as for me, well - you know how the saying goes - it's always darkest before the dawn, and life is good now. for the time being. but i know that if i wake up one day and i'm feeling like a fucking pack mule for people who don't appreciate me, it's time for a massive rapid change, without the period of suffering this time.
> it's time for a massive rapid change, without the period of suffering this time
I massively agree, though I will make the mistake of staying for money again. Whenever I see I can work 3 years at A for every 1 year at B, I can't stomach the loss.
I’m prescribed trazadone for insomnia, and it’s magnificent. Virtually zero grogginess the next morning like I’d get from an anti-histamine, no compromise on sleep quality as the drug actually improves length and quality of REM sleep rather than negatively impacting it as many other sleep-aids do.
My kids have started taking swim lessons at the Y, so i've been sneaking up stairs to run a mile during their lesson. I've thought about strength training etc, but I have no idea what i'm doing on those machines.
Can't say I feel any different, but it is enjoyable.
Pretty much anything that makes your muscles feel sore and doesn't cause injury is worth doing.
IMO: most of what makes fit people fit is becoming aware of their body in detail: how to use muscles, how they work, what they feel like, what they should feel like when they're working together -- all of this builds a foundation where, if they lost their fitness, they would just get it back again.
So if you don't know what you're doing: just learn by doing. Pick something that it seems like your body should be able to do easily, but can't, and fix it. Repeat x100 and you'll be fit as hell.
You can start with bodyweight though. Pushups, pull-ups, etc. I recommend the YouTube channel FitnessFAQs or Calisthenicmovement for a good start there. No nonsense, direct guides with discussion of technique and injury avoidance.
I find the rowing machine is a great cardio+strength combo that you can make as comfortable as you like, and is very low impact (just keep good posture).
Running is a good start. Keep the distance increases reasonable to avoid injury. Enjoying it is important - no need to add anything else until/unless the running gets boring. (Yeah, weights can help, but like you said, can be overwhelming for somebody new to fitness)
It's not perfect, but it was great for getting into the habit 3 times a week. Now I often make up my own sets as I go, taking note of what's sore on me and what I feel could use some work. Doing that gave me the time to do research and get a bit more familiar with how to engage certain muscles, and what machines will do what for me.
> I have no idea what i'm doing on those machines.
Book some regular sessions with a personal trainer. He/she will give you a balanced basic routine and teach you good form.
I was fortunate to have an excellent PT when I first ventured into the gym age 19, a skinny, awkward, scared teenager. The structure of that gym program is still the basis of what I do 30 years later. Different exercises get incorporated, depending on my goals at the time, and variations in # of reps and sets. But still the same general approach.
Strength training is so good for desk jobbers! I recommend joining some small group circuit training or CrossFit groups, where the trainers will show you how to lift correctly and safely.
Just try some pushups, dips, pull ups, and sit ups. Just do a set of a few types each day until your strength is depleted and you will see strength gains.
"Exercise helps post-COVID cognitive decline and insomnia" is absolutely bro science, and especially since it can make the whole situation much, much worse.
That was never the claim. The claim was that it helps with brain fog and mental clarity in general, not specifically that caused by long-COVID, which had been proven to be true.
And a cursory look at the literature for PEM[1] will show you that the recommended path to recovery isn’t “avoid physical exertion at all costs”, but to do what you’re capable of and slowly ramp up the intensity, in which case small amounts of exercise could play a vital role.
Have a blood work checkup. Ensure you'll check vitamin and mineral levels, perhaps most notably vit D and iron. Also check ferritin and transferrin saturation (aids in pinpointing hemochromatosis ie iron overload, which for many leads to brain fog and fatigue and often shows up your age). Exercise regularly.
Holy shit this. I went years undiagnosed. Saw a dozen doctors. Couldn’t get an clear explanation for why I was always tired, brain fog, vision problems, joint pain, memory issues. The list goes on.
Then my _dentist_ of all people ordered a Watch-PAT take-home sleep test (took a lab sleep test, but it was useless) which finally revealed I was having more than 10 events per hour. The dentist made me a Herbst appliance to hold my airways open during sleep. My life is 100x better now.
This is one of the most frustrating things about the US. This shit is expensive. Sure, for a lot of us making bank in the software field we tend to lose sight of that. I got laid off (yay hyper-capitalist bonus chasing management). I'm reading this thread and seeing plenty of things that would be great from a health perspective but let's be real. They're all out of reach for me. Fortunately, that's temporary for myself. I'm sure I'll be back to making bank within a year or two. Most folks however? This advice will permanently be out of reach.
> I've noticed a cognitive decline in myself the past couple years.
How have you measured? I know people do decline cognitively in old age, but 30s is still young. I wonder if people only think they were sharper when younger. I knew much less in my 20s and made tons of mistakes. The mind has a peculiar way of highlighting good memories and downplaying the bad. The person I was in my 20s would not be able to do my current job.
My 30s self also runs circles around my 20s self when it comes to work (writing code), but I’m confident that’s thanks to the knowledge, experience, and wisdom that’s accumulated in that time.
If it were somehow possible to grant my 20s self these advantages, he’d run circles around me. Not just because he’s cognitively faster, but because he’s able to work for longer periods without feeling fatigued and can focus more deeply thanks to having fewer mental background tasks constantly running and not yet feeling the various time-related pressures that come with age.
Giving my teenage self current knowledge would also be interesting. Even though people aren’t cognitively complete yet at that point, at that age I had the ability to get lost in a project on a dime which was was amazing.
It is an extraordinary claim to say that people think as fast in their 30s as 30s. Billions of people have direct experience over thousands of years.
Yes, accumulated knowledge and wisdom can make you more successful with age.
It doesn't mean your fluid intelligence and ability to learn new things is keeping up.
Poor sleep causes significant cognitive impairments in memory, processing speed, etc. Restoring good sleep usually restores most cognitive function, depending on the extent of the sleep deficit. Get a sleep watch or device to track both duration and depth of sleep.
You might want to research Nicotinamide Riboside. I started taking it to see if it would help with painful inflammation in my hands, wrists, and knees and noticed that when I take it, not only is inflammation improved, but my sleep improved (I track with an Oura ring) and I can concentrate for longer periods of time.
Might all be placebo effect, but I’m okay with that. My doctor seems to think that’s probably the case.
It is a shame that NR is quite an expensive placebo, though. I've found similar results, but I have zero faith in it being some sort of anti aging agent in humans.
What makes you the arbiter of discussion? The article is about cognitive decline, this is an anecdote about personal cognitive decline that they believe happened to be caused by covid.
If you think every comment with a personal anecdote tangentially related to the article is “nonsense” and “r/x” material then you must be constantly frustrated by nearly every HN comments section of sufficient length.
It isn't, but at the same time pop culture isn't automatically low quality either. I think blind call to actions based on gut feelings without understand WHY those gut feelings exist are exactly the kinds of things we should discourage here.
I use the collorary for evaluating stuff like this. I care less about a high polished acedemic answer than I do about the resulting discussion not diving into a dumpster afterwrds. For here, I don't see a de-evolution into COVID denailism and anti-vaxxers or even random anecdotes of an off the hinge relative who died and the OP has to be like "I told him but he wouldn't listen", like I would on reddit. I see interesting discussion on a topic that is still a very hotly researched topic even in academia. Ways to potentially get checked or self help to mitigate effects.
No one is an expert on "long COVID" yet, so it's interesting to see experiences (and IMO, see how they age as we learn more about such phenomenon).
Agreed! Similarly, ice baths/cold plunges are a great way for me to mentally “reset” and clear up a little brain fog. Minimizing carbs has, for me, also helped. Not eliminating them mind you, but reeling my consumption of them in to a healthy level and focusing on proteins, fruits, veggies, etc for most of my caloric intake.
Are you taking vitamin d? If not you absolutely should. Magnesium at the same time as D3 and then glycine and another dose of magnesium before bed. This is the magic formula for me.
> Because vitamin D is so good at improving calcium levels, by taking it alone you could be working to increase the calcification of your arteries instead of strengthening your bones so make sure to include K2 in your vitamin D supplement regimen!
Vitamin K2 is what essentially takes calcium out of your blood and puts it in your bones (and teeth). It's something that's rather lacking in western diets and could be a big reason why people in western countries suffer so many bones injuries in old age (and why our teeth suck).
Please note that overtaking vitamin D is unhealthy as well. It’s a hormone and I believe taking too much is damaging to the liver. But supplemental and when having a lack of Sun is probably a good balance.
But if you can be in the sun your skin can make vitamin D.
Note that windows typically block the majority of the radiation that allows you to make vitamin D, so even if the sun hits you every day through your window, it's still not a good substitute for a sunny walk every once in a while. My doctor told me to go out at noon every day, but anything is better than nothing.
Walking doesn't help me for 8 months of the year: There simply isn't strong enough sun to help. December days are only 4-5 hours long anyway. So, I was told to take a supplement from September to May.
My doctor told me to get 15 minutes a day from May through the end of August - and these should be walks with at least the arms exposed (Am in Norway, so this isn't always possible for me, the immigrant). Walking alone isn't always enough.
I bought a load of UV-B flo tubes with a desert profile and rigged them up over my bed which would go upto the ceiling and then they would come down in order to bask under for hours. I could control how far away from me the lights were so I could move have them closer to me for a quick 30mins or have them further away for spending 2-3hrs underneath them.
I'd go to sleep under them, just dont have them too close to you though otherwise you will burn but never tan.
Nearly all Glass and Plastics block UV-B which is needed to make Vit D. UV-A found in tanning salons oxidises the melanin pigment aka the sun tan and melanin converts 99.9% of UV radiation and converts it into heat, so the suntan regulates how much pre-vitD can be made by the skin.
There is a corrugated plastic sheet (2mx1m) which allows UV-B through, but it needs replacing every few years as it breaks down and its expensive!
You have to go really overboard with vitamin D3 to take too much of it. The daily recommendations so far are underestimating it. 4000 IU should be fine for adults. There are people that take 6000-10000 IU, but it's hard to say whether they might be suffering from some long term effects due to this.
You should take vitamin K2 with D3 though.
>But if you can be in the sun your skin can make vitamin D.
This is harder than people say. You need UVB light to hit your uncovered skin (glass blocks it entirely). The sun needs to be above 35-50 degrees in the sky. If it's below that (like in winter or evenings) then you won't get vitamin D from it.
I doubt it is much to do with COVID. Mid 30’s is about the time when you have to start paying closer attention to things like sleep and exercise or everything starts to go to shit.
I'm in my early 40s, and do nothing specifically for my physical health. I don't have cognitive decline, I don't suffer from little issues at all, (someone once said that'll happen once past 40), some days I skip sleep entirely.
I also learn new stuff and program on projects, which are cognitively demanding, almost every single day. I don't regularly watch TV shows. On occasion I binge-watch something, only to stop it again for many months. I don't drink alcohol at all, but I consume small amounts of THC.
Your "mid 30s" claim might be true for people who are doing it wrong, which probably/likely is the vast majority, but there's absolutely no fair and objective way of putting an age on the beginning of cognitive or physical decline as if it was outside of ones personality responsibility/abilities to prevent it from happening until a much, much later age.
But ... to be the exception that agrees with the rule: If I lived how most people around seem to be living, I'd likely suffer from decline as well.
Not OP but I had terrible covid at 38y old around march 2020. My chest xray showed one of my lungs was really bad , and during 3 months I was feeling like crap (includingthe brain fog and all the stuff people mention).
Fast forward 3 years, I go swimming thrice a week, and it sucks that STILL my breathing hasn't recovered. If I try to take a lot of air for several times, I'll start coughing. I get out of air quickly... even though I have strength to keep swimming.
Scientists may have found mechanism behind cognitive decline in aging, but there shall, in that time, be rumors of things going astray, and there shall be a great confusion as to where things really are, and nobody will really know where lieth those little things with the sort of raffia work base that has an attachment that one may confuse with clickbait.
At this time, a friend shall lose his friend’s hammer and the young shall not know where lieth the things possessed by their fathers that their fathers put there only just the night before around eight o’clock.
And what a tragedy that would be. Positively unrecoverable, we might end up remembering we’re not experts, this is not a scientific website, and fun/excitement/entertainment is a good thing.
I don't think it has to be as binary as "nothing" or "we found the cure for cancer".
we do these experinebts on mice due to similar-ish brain chemistry. It hopefully leads to controlled human studies and then we start devloping medicine that way. It's always a process.
Fingers crossed that it can actually be replicated in future studies and research. We definitely don't want another nearly 20 years of false path ass busting research based on falsified documentation like we ended up with on Alzheimer studies.
No. There was a drug released that targeted that pathway, but the approval in and of itself was a scandal - I spoke with a pharmacist last night who said people at her hospital were disgusted by the FDA’s decision. It was removed from the market two weeks later. There was basically no evidence of efficacy.
Not in the face of such overwhelming evidence; it’s literally their job to make sure things are effective. It turns out medical studies are weaker evidence than anyone would like, but here there was quite compelling evidence that it was useless!
There are several controlled studies that show phenylephrine does absolutely nothing better than placebo for congestion, yet it's the #1 medication sold and available in the US for congestion.
The article suggests that decline in nitric oxide availability as you age under pins the effect studied. Citrulline has been found to be an effective route for improving nitric oxide levels by synthesizing into arginine, which is destroyed in the gut while citrulline is not and readily converts into arginine.
I think they may have found one mechanism or one part behind
the cognitive decline in aging.
I am certain there are several different processes that
contribute to it and finding all of them and then mitigating
those may have side effects in other parts of the brain.
I have an extremely speculative and not based on science that
the brain simply is not meant to function forever.
We extend life in various ways, and we get better at it.
Perhaps in a couple of decades people will live (be kept alive)
for 100 years on average. (well those who live in a country
where such medication and treatment is available and at some
level affordable)
But human evolution has not caught up with the prolonged life span
since living that long has been an exception for 300.000 years and
looking farther back in evolution probably millions of years
Also, cognitive decline has been studied intensively enough that if there were a single mechanism responsible for most human instances of it, the science around that single mechanism would've been settled by now. Instead what we seems to have is a disease where toxins, chronic infections by bacteria, viruses and fungi, cardiovascular health, genetic variability (e.g., apoE4) and metabolic-lifestyle factors like insulin resistance and lack of sufficient exercise are all important.
But HN likes to upvote these announcements written by PR departments at universities.
I'm more interested to hear what discoveries have lead to meaningful results. There are a lot of news articles on potential medical breakthroughs but I have no idea how medicine is actually advancing.
If one added that specification, it would change the meaning that David Kelly seems to have intended. (It would change it to what the poster understood.) Kelly does not seem to restrict the matter to mice, as Uli Bayer does not seem to.
> This isn't what the title says or implies
It is what the submitted divulgational article from the University writes, and the title follows.
> He pointed out that this would only work in normal age-related cognitive decline, not the decline seen in Alzheimer’s disease and dementia.
That's an important distinction. Alzheimer's disease is a specific problem, separate from long-term cognitive decline. That the mechanisms of both have been identified is real progress. One way medicine progresses is by differentiating causes of the same symptoms. Then specific treatments can be worked on.
>Normal aging reduces the amount of nitric oxide in the body. That in turn reduces nitrosylation which decreases memory and learning ability, the study said.
Has viagra shown affects at reducing normal aging in the brain? It seems to do so in the heart.
Ideally, we'd identify the key mechanisms at play and be able to develop lifestyle modifications that would support them, but it's pretty cool that these drugs have benefits beyond just better bedroom performance.
I’m not sure what the proper name is for this idea, but I consider ageing to be a trade-off between cell-regeneration, which maintains youthfulness, and mutation-limitation, which reduces the chances of cancer. That is to say, if you “aged less”, you would get cancer more/sooner. Everything else, like the balance of chemicals in the body, I assume would be downstream of that.
Telomeres are just repeats at the end of chromosomes to allow for replication. They aren't directly involved in replication fidelity beyond allowing for replication to proceed. I guess protecting genes near chromosome termini but that's different than the mutations you would expect in cancer.
I'm sorry for the delay, but this actually isn't quite right. Short telomere syndromes are not associated with cancer. In fact, it is long telomeres that have a strong association with cancer (largely because aberrantly activating telomerase can drive cancer development.)
Research now more or less always proceeds bottom-up so that it's never possible to determine causality from results. Everyone looks for causality, researchers look for positive results and the wheel keeps on turning.
When top-down thinking disappears, science enters a cognitive decline of its own. This one is contagious.
Those kind of articles (and papers) would be far more impactful if they were used only when they actually referred to some major real breakthrough.
As opposed for us to read 1000s of them in the span of 10 years, and nothing ever coming out of them - except 200 more articles like that from other teams, on other competing mechanisms.
What about a more real title: "Scientists found a potential mechanism behind cognitive decline in aging, but it's more likely that they have not, the area of study is very complex and ill-understood still, and it will take decades at best to discover and verify any definitive mechanisms. More likely this study also has methodological errors or these guys are even padding their numbers to get a paper published and secure more grants".
Yes, it's a mouthful.
How about "Researchers find a way to induce cognititive decline in lab animals. Don't hold your breath for human relevance".
Eventually we will reach a point where humans are immortal. They’ll still die if they’re shot or clog their arteries etc but they won’t die purely based on running down a clock.
There’s no inherent reason we have to die. It’s an evolved strategy to allow newer models to replace us. Turn that off and you’d stay around until physical damage and irreparable decay takes you out.
It will be interesting from a societal standpoint. You’ll have the real scum people wanting free immortality and people arguing they should get it even though they’re horrible. You’ll have the rich people who want to keep it to themselves because the poor don’t deserve it. Things like prison sentences and the general value of time would all be messed up.
> [death is] an evolved strategy to allow newer models to replace us
I don't think that's true and it's pretty difficult to argue that it is given how close to universal death is among living things... if it were true evolution would also have explored the adjacent possible of near immortality more often. After all living longer also means potentially producing more offspring, so it's not an impediment to natural selection. Probably more accurate to say that between the complexity required to keep repairing the accumulated damage in an individual organism over time and simply replacing the organism with a new model every so often, evolution prudently chose the later. Evolution is economical... making highly complex systems that are eternally resilient and repairable is not.
I don't doubt we'll soon be able to extend lifespan (and healthspan) by quite a bit but not indefinitely unless we can transfer the mind to a new body. And frankly I doubt that makes a lot of sense because I don't think 200-year-old me will feel much identity with 20-year-old me anyway. The Buddhists probably have it right that the sense of a continuous self is largely an illusion.
Who is to say we are not reaching the levels of irreparable decay or physical damage to render death more likely? Instead of death, how about the years or months before the eventuality where we are losing our capabilities in a variety of methods? I say we are reaching this type of milestone you have spoken about in your comment. Even the tidbit about rich people hogging resources because they are doing exactly that right now!
I say this because I do believe that a lot of research into aging is just finding a lot of strange oddities in our genes, and biological mechanisms. There was never any long term biological process such as natural selection, darwinism and survivorship bias to remove or refine them into something that works better or works for indefinite lengths of time. It is only recently that more humans are able to live 60+ years and that there is billions of humans compared to the numbers of live humans in previous centuries.
Immortality raises a lot of ethical and philosophical questions that we will need to tackle if it ever becomes real. For example, if you live 200 years, how much would you remember of your first 30 years of life? Will that 200 year old person still technically be the same as the one that was born if he hardly remembers anything?
I'm a good bit younger than 200 and barely remember large portions of my earlier life already. What's so special about 200 that makes it any different?
In another comment I spoke about how many more people are able to reach 60+ years of age, and that the amount of people living longer have exponentially grown. Our world population reaching another billions milestone at faster timeframes. Scarily, life expectancy was always at around 20-30 years for a large portion of history for humans.(most who reached 15 years of age were capable of living to 50 years albeit they were considered to be outliers) Around neolithic times, we had moved towards increasing population density and promoting growths. This time period was odd as it lowered the overall life expectancy because there were more humans that died from other methods as lifestyles changed from hunter-gatherer to more sedentary lifestyles. Hunter-gatherer lifestyles required loads of land for a single human to survive, which the neolithic era had been able to fix with the introduction of farming. Due to density, more people started attacking one another for variety of reasons and heavily relied on farm crops to sustain increased human populations. Societal growth of centers such as towns and cities then countries continued. Excluding many outliers, life expectancy only started to rise in the 1950s and has kept further increasing past 50+ years and 60+ years.
So yes there is something special about reaching 200 years of age. As it will singal a milestone no other human has ever reached from all of history. On the other hand, life expectancy growing at an alarming rate is putting a lot of strain on resources and land availability.
So by your logic we should be trying to reduce human life expectancy?!
But honestly I really don't think these arguments are motivated by/a consequence of real belief in them, it's more a kind of cope with the current situation that we've become acclimated to, something in the vein of "if god intended men to fly they'd have wings".
It is ignorant to not plan on methods of habilitating more people. There is an unsolved problem of space constraints and transportation costs of essentials and optional resources. Reducing life expectancy and population will not solve these fundamental issues. If these two constraints are able to be solved sufficiently enough, then people will be able to live in larger swaths of land or in outer/near orbit space or within the oceans. It all depends on how we progress from here. Right now we are having the same issues that plagued the neolithic era. Our increase in population and life expectancy will end up hurting us because of the unsolved logistical issues.
Due to the way medication is developed, we basically only end up with medicine that works on humans + at least one other species.
I wonder how many medications we have missed out on that would have worked on humans but never got to the human trial stage because it doesn’t work in any of the animal models we use.
And a condition we can induce in another animal. If we can't cause it in another animal then we can't test a drug against it. There are a lot of diseases that can make no progress under this model which we can not induce in animals or humans.
Fascinating! Reminds me how machine learning as a field is often focused on tasks that can be quantitatively evaluated using large datasets. There are a lot of tasks that do not fit this model, especially interactive tasks.
Not really sure what you're getting at, teratogenicity only matters if a person is pregnant and lack of teratogenicity is in no way a requirement for FDA approval.
There are many commonly used drugs with teratogenic risks that we discontinue in pregnancy or counsel the patient on, picking randomly from a list of medications that were approved in 2023: sparsentan
I'm not sure if I'm missing something but why are you thinking teratogenicity matters when the vast majority of patients are not pregnant at a given moment?
I misread your comment as "meth" the first time and I was like... well I guess that could theoretically help. You know, aside from the neurotoxicity of meth.
I take dextroamphetamine for ADHD, and even though it's a lot less toxic than meth is, I still have to take frequent magnesium supplements or else my magnesium levels totally dive (confirmed by blood tests).
so "scientists baffled and confused" would have been more accurate :)
edit: I'm overthinking this, but the word "scientists" does a lot of heavy lifting in the headline. The number of things the human race in general and scientists especially are unsure about is vast. Putting a person in a white overcoat, spectacles, and pen in their pockets to lead the sentence with authority doesn't give them a chance of not looking dumb. Scientists in media language are 100% of the time more clownish than even politicians or any other profession.
Even the content in itself is garbage, in which case the headline does justice, or there was in fact something news-worthy but the meta-analysis by this article has missed it.
> Bayer said that aging in mice and humans both decrease a process known as S-nitrosylation, the modification of a specific brain proteins including CaMKII
While this is true, the same protein, even the same gene, often serve different purposes in different species. So even if we figure a problem out in mice down to the gene level it might not yield any results in humans. That's also the reason why the majority of drugs that have a positive outcome when trialed on mice don't yield positive results in human trials.
I wonder if one could even guarantee a quick and early death without suicide. I assume if you join the military or something, if you get shot on the battlefield you could end up surviving with extreme pain, or bleeding out over a long period of time, neither of which are particularly desirable. There are various ways to go to sleep and never wake up, but I'd assume anything you did intentionally would be suicide.
Some people aren't against committing suicide, but assuming you were someone who's afraid of death (so can't just commit suicide) but still doesn't want to live into their later years, what could you even do? I assume just increase the chance of accidents, but what kind of accident would result in death with minimal suffering?
But, most people I've come across that are outward with this attitude say they smoke tobacco to help, and have a suicide method all planned out and ready to go as a guarantee.
Ah, so that's where the saying "do you have a death wish?!" came from :)
> But, most people I've come across that are outward with this attitude say they smoke tobacco to help, and have a suicide method all planned out and ready to go as a guarantee.
Having a plan and having the guts to carry it out are two different things. I've attempted suicide twice but chickened out both times. Honestly glad I didn't go through with it.
Some tell-tale signs (I work with GPT a lot as I mentioned in a sibling comment):
- It's a list, it's numbered, it's got pretty consistent markdown formatting. This is especially present with ChatGPT
- Title Casing In Each List Item
- Strong usage of the passive voice
- Strong CYA tone. "might promote", "studies suggest", "has been associated", "can convert", "possibly lowering", "thought to increase"
The general structure is very consistent with GPT too. Once you've seen a lot of sessions it's just... plain obvious. Especially if you step back and think: "Would people actually.. write like this?"
GPT4 can generate some extraordinarily high quality text if you know how to prompt it. But this ain't it - it's some of the most boring way to prompt. The OP's response is what happens when you prompt with some article summary and a "What are some possible ways we could increase the production of nitric oxide in the body".
And no, that trashy CYA tone is not "precision", if anything, it's vagueness. It's weasel words.
> no, that trashy CYA tone is not "precision", if anything, it's vagueness. It's weasel words
That is not what I said. /That/ «trashy CYA tone is not "precision"». But some use similar expressions to those you noted in order to be factual.
Some texts give a strong impression of fakery; some texts could give a wrong impression upon brutal use of raw Bayesian indicators. Signs orient, do not decide. Hints are not proof.
Some patterns in LLM output can be caricatures of proper efforts (factuality for precision, when relevant, is one of them).
So, people may write similarly to that. (Only, hopefully, well beyond veneer.)
Brief summarization that seems redundant to the topic because it's the model priming itself to generate a response in the requested form, which is usually a:
3-10 item list which mentions certain phrases related to the prompt every time ("nitric oxide" here).
It very likely bears a close resemblance to a member of the theoretical set of all well-formed answers.
Problem is all the other sets it belongs to, including the set of all answers containing unverified factual statements, not to mention the set of answers that resemble the output of a large language model.
Chatgpt loves lists like this, then length and "tone" can be the most obvious indicators. You can modify those attributes through prompting but that should help find unmodified output
If you need to use mouthwash to prevent bad breath even when you brush your teeth and clean your mouth properly, you need to look into what might be causing that problem in the first place. Mouthwash is like a duct-tape workaround and probably not very healthy for you either.
Btw - interdental toothbrushes. If you’re not using them already, you may want to start. Very helpful. Much better than flossing which has some problems associated with it.
It's better to think of your body as a walking city of interlinked organisms of different species than a single organism. They need you as much as you need them. Killing off some of those symbionts can have negative effects for the other party (you).
Mouthwash is indiscriminate in that it kills of a huge amount of bacteria, but some of those are actually useful.
> It's better to think of your body as a walking city of interlinked organisms of different species than a single organism. They need you as much as you need them. Killing off some of those symbionts can have negative effects for the other party (you).
> Mouthwash is indiscriminate in that it kills of a huge amount of bacteria, but some of those are actually useful.
> It's better to think of your body as a walking city of interlinked organisms of different species than a single organism. They need you as much as you need them. Killing off some of those symbionts can have negative effects for the other party (you).
> Mouthwash is indiscriminate in that it kills of a huge amount of bacteria, but some of those are actually useful.
Floss once or twice a day, maintain gum health, and watch your diet. You don't need mouthwash. (Anecdata - at my most recent visit, my dentist told me to come back in 18 months.)
Ohhh, I misinterpreted your comment. I think other people did too.
It seemed as if you were saying that your dentist told you not to step foot in the dentist office at all for 18 months. But you just meant, the literal dentist doesn’t need to see you. Got it. I feel like this isn’t out of the ordinary now.
I always hear every 6 months for a cleaning. This new “3-month” information takes a bit away from your original statement since you are doing a bit more than what you suggested is required for maintaining healthy oral health.
Leading back to my original joke, maybe your dentist insisting that you need to get your teeth cleaned every 3 months is how they make their money lol!
'Leading back to my original joke, maybe your dentist insisting that you need to get your teeth cleaned every 3 months is how they make their money lol!'
They make their money from implants and advanced treatments costing multiple thousands, not the £100 hygienist fees.
A hygenist, plus a nurse, seeing a maximum of 8 patients a day at £100 a time isn't a business I would want to be investing in.
My dental hygienist explicitly advises against mouthwash use.
IIRC the argument given to me was that the bacteria in the mouth eventually build up a resistance to the mouthwash, i.e. similar concept to antibiotic misuse.
Good diet, correct brushing twice a day, and correct flossing once a day is all that is required. Along with an annual visit to the dentist.
What you listed here is essentially an evidence based diet and one of its most prominent proponents is Dr. Michael Greger with his works around "How not to die".
I really want to know, why don't we all supplement with L-arginine long term? Time-release capsules are available and I have taken for numerous issues like RSI to great success. Whats the downside to long term usage?
Side bar : L citrulline is thought to be more effective than arginine.
One downside that I don’t see discussed much, as I’ve watched multiple recalls over recent years for supposed contamination of things like tmao and other toxins in either the manufacturing process or packaging process, I wonder how many supplements are contaminated. I have never seen an analysis even from the vendors who do pretty hefty chemical composition analysis.
> I wonder how many supplements are contaminated. I have never seen an analysis even from the vendors who do pretty hefty chemical composition analysis.
Why do you think food supplements would be more contaminated than other processed foods? Or even things like toothpaste or shampoo, those are also made from highly processes ingredients.
There's a large amount of precedence, that's why. Rather than asking the room, one would think the first step would be to obtain information and inform yourself.
Why so defensive? I'm asking the room because it's a smart room, usually, and often there's someone who'll be far better informed than I could be with a quick search. That's literally why I spend time here.
Regarding your links, I'm sure I could find similar studies about nearly any kind of food. I have a friend who won't eat peanuts because he's afraid of aflotoxins, which are real, genuinely dangerous, and if you think that peanut products are tested well enough to 100% guarantee the aflotoxins are always below safe levels in all peanut products you'll ever eat... Well, I'll disagree.
So again, why do you think supplements are worse than other food products? I don't agree that your links answer this question.
They do show that there's often contaminants in supplements. They _don't_ show that supplements are unusual in this regard when compared to other food products.
Your third link focuses on heavy metals in supplements. Here's a similar study showing they are also in baby food:
So is it just supplements and baby food? Unlikely. More likely it's that supplements and baby food are both things that make people worry about contamination, so they test them more. Meanwhile your ketchup might be loaded with all kinds of contaminants but you'd never think of testing it.
"These things are also contaminated" is shoddy argumentative reasoning at best, it is not the "got ya" that you think it is . I never claimed that there aren't contaminants in food, and I don't see how it defeats my claim that dietary supplements are unsafe -- the FDA is more stringent in regulation and testing with respect to food, as opposed to dietary supplements, because, you know, we need to eat to survive.
One would think the first step would be to look it up.
> Most healthy people do not need to supplement with arginine because it is a component of all protein-containing foods[15] and can be synthesized in the body from glutamine via citrulline.
I do not understand how someone can wish to know something, but refuse to expend effort to obtain the information they wish to seek? I hope it would be ok for you to explain this behaviour, please?
This seems unfairly aggressive. GP asked what the downside is to preventatively taking l-arganine as a supplement, your quote addresses only whether it's required.
In short, you can't test your own blood so you don't know when your levels may be low. If there were no downsides to constantly supplementing then what reasons may there be to not do this?
It is unfairly aggressive and they did this twice just in this thread. The other was here:
> There's a large amount of precedence, that's why. Rather than asking the room, one would think the first step would be to obtain information and inform yourself.
I don't know why this person feels the need to roam around the conversation policing how people are engaging in it. It's incredibly obnoxious. Especially frustrating given that they do seem to have some information to share, which they could do and just omit the completely gratuitous and unwarranted hostility.
I clearly made a point of inquiring why the behaviour was performed, it was an honest inquiry, I am genuinely curious.
For what it is worth, my context is that I have seen the behavior of asking the room, or even just throwing out conjecture to the room, without properly doing research beforehand, to be a common flaw within computer scientists and within "tech workers" as a demographic. I had to put up for a whole year with one person making up what was complete and absolute nonsense through first principle reasoning, rather than just reading a 101 Sociology book, which would have answered all his questions effectively and with some basis in research. It is also something I see commonly within the Hacker News comments -- someone will ask a generic question to people in Hacker News, rather than doing even a cursory form of searching first. I do not understand the idea implied through this behaviour, that a random tech worker will know more than people whose job is to study the questions that are being asked, and so I resolved to ask this person, taking care to be polite, why they choose to engage in this behaviour.
If what you consider “polite”, several people call out as aggressive, then maybe you should re-evaluate your definition of the word.
Your comment does not read polite. At best, passive aggressive.
Asking questions fosters discussion. For a site centered around discussion, that seems warranted. Telling people to just look it up is pretty much the antithesis of discussion.
> Telling people to just look it up is pretty much the antithesis of discussion.
On the contrary, the quality of discussion would be much higher if people took one entire minute beforehand to research something. It is shameful and disappointing that the techbros here cannot be bothered to do this, and prefer to live in ignorance.
My quote answers the question of "why don't we all supplement with L-arginine long term" with "it's in basically all protein containing-foods, so it is not necessary".
While you are right there may be individual variation, the rule of medical advice is that we cannot assume what we do not know, and preventative ingesting of a substance that is not too well understood may have unintended side-effects. Especially in the case of molecules that have been synthesized.
As my other comment within this thread states, there is a high precedence for contamination of health supplements as a whole, so in this instance preventative dosing would seem to put someone at more risk than e.g. just eating more protein.
In addition, the supplements may contain vastly higher quantities than are safe to absorb. For example, there was a recent pubmed paper describing an incident where +500mg doses of Vitamin C (which is 1/6th of the EFSA and NIH's estimates of "safe upper limit") taken daily over a long time caused kidney stone formation. This required expensive surgery to correct.
For what it is worth, as someone with a damaged and resectioned gastrointestinal tract -- the dieticians I work with prefer to solve deficiencies with eating foods that contain the given micronutrients rather than supplementing with them. One doctor told me I had a copper deficiency, he told me that taking copper supplements tends to cause gastrointestinal distress and would have been too high a correctional dose, and so his solution was to increase my consumption of dust (which is how we naturally get copper) through obeying the five second rule. This wasn't especially out of the norm. Selenium deficiencies were solved by eating tinned tuna, likewise vitamin B12 deficiencies were solved by ingesting liver occasionally, etc.
If you suspect that you are deficient in a given micronutrient, it is always better to explore that possibility with your doctor than to take high quantities of unreliably tested substances.
That doesn’t necessarily answer his question though and doesn’t even seem like a well reasoned point. Just because your body can produce something doesn’t mean it can’t benefit from more.
Likewise just because your body requires something doesn't mean that large doses of it are beneficial. See my followups, which address that and were written 30 minutes before your post :/
Arginine has good short-term endothelial effects but bad long term effects. Most studies last <1 month observing the good effects but not monitoring future bad effects:
Most of the problems with NO production happen during the night when people tend to breathe through the mouth, making them tired during the day. Moreover, their CO2 levels tank as well for a double negative effect from what was supposed to be a refreshing sleep.
> Nitrate-Rich Diet: Consuming foods high in nitrates, such as beetroot, leafy greens, and other vegetables, might promote the production of nitric oxide.
I don't think maximizing dietary nitrate is a good idea, since the nitrite that's an intermediate in this pathway is definitely carcinogenic (forming nitrosamines).
Have you only tried it raw? There are ways to cook it without losing too much nutrients. Cooked kale still has noticeable health benefits according to some studies I found.
You should try it southern or soul food style similar to how collard greens are cooked. It’s cooked along with meat and a bunch of seasonings. Definitely a different flavor. But also less healthful.
Just as a personal opinion: I hate the way kale tastes. I also hate coffee. I love broccoli and tons of other greens. I love tea.
The only way I enjoy kale is having it as garnish that gets tossed away.
my better half loves steamed kale. no amount of salts and seasonings has changed my mind. cheese and salt/pepper took me from a broccoli hater into a broccoli lover lol.
Chop it small (the stems really small) add sliced garlic, sliced hot pepper, some olive oil and a cup of water then cook it for 3-4 minutes only. Drink the water and (if you must) serve with lots of cheese and bacon. (add the cheese immediately or it wont melt)
Like with broth, the first day it tastes good. If you prepare it again within the next 2 days the body screams for more. Specially the water is funny, it feels as if some magic potion.
I was comparing various ways of boosting my nitric oxide at the time. I could see it visibly (increased red complexion) and my cognition also improved. Subjective, yes, but that was good enough.
Betaine is another thing to look at. One of the cheapest supplements, no (or very low) toxicity, and seems to regulate NO metabolism, among other things.
+1 on L-citrulline, caution on supplement quality - many manufacturers sell 2:1 citrulline malate to reduce costs which means you effectively need to double the dose to actually consume a given target dose.
Nitric Oxide dilates the nasal passages and is also a vasodilator as well. A simple n=1 test is to do nasal humming and test blood pressure before and after. I can typically get a (temporary) 10 point drop.
Nitric Oxide is also anti-bacterial and humming may help clear sinus infections.
same mechanism for decline in the rest of the body???? Surely oxidation and dna mutations accumulating affects the brains similarly to how it affects everything else.
I mean I'm sure that eventually entropy will claim all of us, but it'd be really cool to be able to help people maybe not extend their life times but be less miserable during them
I think I would hate losing my cognitive function if I realized it was slipping away a lot more than needing to use a wheelchair
IIRC, brain cells don’t divide, so “random DNA changes” don’t apply, at least not in the way it would in the rest of the body. I could be totally wrong, I’m not a brain scientist.
This should be the title of the article. Honestly these supposedly dissemination articles do not offer much more than reading the abstract or skimming a bit through the article itself.
https://www.science.org/doi/10.1126/scisignal.ade5892