In old humans, the capacity of producing new blood cells becomes reduced in comparison with young people.
The study has identified as the cause why the stem cells which produce blood cells are less able to do that in old people is because they are less efficient in autophagy, i.e. they are less able to destroy the cellular components, e.g. defective proteins, which are no longer needed and which must be recycled.
After identifying this cause, they have studied a few methods by which this autophagy capability of the stem cells can be influenced.
The simplest method was a treatment with gamma-linolenic acid, a fatty acid that normally can be produced by a young human body in sufficient quantities, but in old people its synthesis rate diminishes, like also for a few other substances, e.g. for long-chain omega-3 fatty acids.
The treatment with gamma-linolenic acid was tested successfully both in mice and in human cell cultures, restoring the ability of the stem cells to make new blood cells.
A very potent way to induce autophagy seems to be through fasting [0].
As far as I understand measuring autophagy accurately across different cell types in a living organism/human as autophagy flux is still a big challenge and e.g. Peter Attia emphasizes in his podcasts there is no reliable way to effectively measure autophagy, unfortunately he didn't bother to go in depth. The papers I've found about measuring autophagy are painting a more confident picture, though.
So this interesting review [0] from 2017 is very cautious; from the last paragraphs of the concluding remarks:
>Detection of autophagy markers such as LC3-II and/or of accumulation of autophagy substrates such as p62 has been attempted using autopsy or biopsy samples from human patients. However, static analyses cannot distinguish between autophagy upregulation and degradation inhibition, and an increased amount of p62 is not necessarily caused by inhibition of autophagy as described above. Furthermore, human samples are often limited in quality due to difficulty in obtaining fresh tissues, thus the data need particularly careful evaluation taking into consideration possible effects caused by sample quality and preparation. Presently, there is no established method to measure autophagic flux in humans; therefore, it remains practically impossible to monitor autophagy properly in humans. Static analyses with the limitations stated above are often misleading, or can provide only suggestive results at best.
Genetic mutations in humans that may cause changes in autophagic flux have been studied using patient-derived cells such as fibroblasts, lymphoblastoid cell lines, or induced pluripotent stem cells differentiated into the affected tissues. Autophagic flux can be tested properly in these cells ex vivo. How much the results using cell types differing from affected tissues, or how much the defects observed ex vivo reflect the pathology of patients and the cause of symptoms remain to be addressed.
This newer review [1] is also cautious but a bit more optimistic:
>Should we aspire to have a definitive autophagy assay? It depends. Given that this pathway is part of a larger endocytic and metabolic signaling network, there will always be a need to investigate mechanistic questions using different assays. With that said, the field could benefit from having an endogenous flux readout that works across cell lineages without the need to engineer cells up-front. Imaging and analytical probes delivered exogenously to cells, animals, and patients could be envisioned here. Moreover, detection of circulating autophagy by-products and/or molecular responses to pathway modulation could be investigated as candidate biomarkers (see Outstanding Questions). Taking future innovative steps towards the measurement of autophagy will greatly enable the discovery of fundamental mechanisms and the development of autophagy-based therapies. In the clinic, such biomarkers will provide an early and robust view of therapeutic target modulation, which will drive decisions around adapting dose schedule and intensity, which will bring greater benefit to patients.
And this commentary [2] is quite optimistic:
>The control of autophagy manipulation and the measurement of autophagic flux in vivo remains challenging, yet it is a crucial requirement for the safe and finely controlled application of autophagy manipulation in the clinic. The current techniques to measure autophagy accurately may already exist, but have to be aligned to operate on the one hand in a multi-scale fashion and on the other hand to be suitable for high-throughput high-resolution quantitative analysis in a living tissue and organism. Here we have provided examples for how we may address some of the challenges around measuring autophagic flux in vivo, how to discern steady state and the maintenance of a suitable autophagic activity, how to assess autophagy drugs for their potency and to correlate these data with disease-specific markers of cargo or health. Future application of these aspects using living model systems, for example, viable transgenic murine embryos or candidate tissues that express the required autophagy markers, will be of high value to provide answers and the resolution to further build on the pioneering work that targets autophagy assessment in vivo and in the clinic, thereby assembling a picture of a systemic autophagy status.
Are there any "good" resources that explain "proper" fasting? The Internet seems to be chock-full with information of questionable provenance.
A personal example. When my wife and I started keto and intermittent fasting we choose the 8/16 schedule and only ate between 12:00-20:00. I was having a conversation recently with a client, family practice doctor, he said I wasn't really intermittent fasting. I was just skipping breakfast. So who knows.
What we did worked well until it didn't. With low carb, <20g; low calorie, < 1300 kcals; and fasting. I lost 60-70 pounds in 2 years. Then I started gaining it back, I an up 40ish. As I understand it now, I have been shorting my calories too much and my metabolism has tanked.
I dunno, I just know that if anyone complains of any malady here on HN, the fastoids will jump on them like white on rice. It's like /r/nofap for techbro types.
Because it is a fantastic summary by a medical doctor that is becoming personally convinced. It presents an overarching narrative of two bodily systems that cannot very well operate at the same time, the second of which operates during periods of fasting because (in part) of the reduction in insulin, which essentially "triggers" the competing, de-facto mechanism.
You probably guessed it, but the autophagy-inducing bit happens as part of that second, insulin-supressed process.
He advocates a 3-day water-only fast once a month (for himself). I personally switched to a one-meal-a-day plan for 3-4 days a week, and am trying to build up to 3 day fasts 1/m.
What clicked for me recently was the insulin story. Keto, 8/16, multi-day fasting, etc all seem to be tied together under the "reduce time spent with floods of insulin" theme. It wouldn't surprise me if any of them are fine, and advocates of "the one true IF" are just being territorial.
Diet is unequivocally NOT the root cause for all major illness. "Many of the most common illnesses are substantially affected by diet" is a more sane claim. There's plenty of death and disease to go around though even after you control for all the lifestyle factors. Even vegan marathon runners get cancer.
5FA is a chemotherapy drug but a myeloablative agent as well. As a side effect, it supresses the ability of bone marrow to produce blood cells. That’s why it’s used in this study.
Pretty important distinction: Linolenic acid is the family of alpha-linolenic acid (ALA) - which is omega-3 ; Linoleic acid is in the family of omega-6
If the young were very well-compensated for the inconvenience I don't actually have a huge problem with this kind of reverse wealth transfer. Try to balance the scales of the social security and housing market wealth extraction which is (in a metaphorical but more meaningful sense) bleeding the young dry.
Giving blood isn't really a big deal for a healthy person.
This begs the question, is a Hospital legally able to resell that tissue to the cosmetic industry. Seems more likely that an abortion clinic would be an easier source, if it was illegal, due to fewer people needing to be corrupted.
It doesn't seem like Sandra was concerned with how it was sourced at all, other than it came from Korea. The "banality of evil" I guess. Combined with her vanity of trying to look younger. Is why this interview stands out in my mind. Plus she's 57 and has a reputation for looking unusually young for her age.
"Blackcurrant seed oil for prevention of atopic dermatitis in newborns: a randomized, double-blind, placebo-controlled trial"
"Clinical & Experimental Allergy, 2010"
"Background: The present increased incidence of atopic diseases has been associated with an altered intake of essential fatty acids (EFAs). The composition of blackcurrant seed oil (BCSO) corresponds to the recommended dietary intake of EFAs, and as a dietary supplement could, in small doses, modify the imbalance of EFAs in an efficient way."
"Objective: To assess the effect of dietary supplementation with BCSO on the prevalence of atopy at 12 months of age."
"Conclusion Dietary supplementation with BCSO was well tolerated and it transiently reduced the prevalence of atopic dermatitis. It could therefore be one potential tool in the prevention of atopic symptoms when used at an early stage of life."
The first time I heard about it was while monitoring medical news about treatments during the epidemic - because researchers in Pakistan, then Saudi Arabia, gave credit to the idea of trying Nigella Sativa. See e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364675/
> Borage oil contains amabiline, which is a pyrrolizidine alkaloid that is toxic to your liver. The more borage oil you take, the greater the risk of liver damage from this substance, per the Memorial Sloan Kettering Cancer Center. Look for borage oil certified free of unsaturated pyrrolizidine alkaloids to reduce your risk.
> The protocol comprised of 60 daily sessions, five sessions per week within a three-month period. Each session included breathing 100% oxygen by mask at 2ATA for 90 minutes with 5-minute air breaks every 20 minutes. Compression/decompression rates were 1 meter/minute
So the main problems listed are inflammation, lack of omega 3 and reduction in some kinds of autophagy. All of these can be addressed with an animal based diet or a keto diet plus intermittent fasting. The more I look into it the more I am convinced that a high fat animal based diet with fasting is the healthiest diet.
"Our doctors have made such astonishing advances over the last 7 years, our medical knowledge doubling in that time, that I think if I'd only been born another 25 years later, then I am sure they would easily relieve me of my asthma."
--- Laurence Stern, writing in Tristam Shandy, in 1759. He used the word "asthma" to refer to the tuberculosis that eventually killed him. As for a cure for tuberculosis, he was wrong by 200 years.
As far as I know, this was the first prediction of steady advances in medicine, as well as the first use of the trope "If I'd only been born 25 years later, doctors could cure me."
I wonder if anyone has tried to map scientific progress in some quantifiable way, and if so, whether or not it matches punctuated equilibrium. It does seem as if there are periods of time in which we make steady progress, and once in a while leaps and bounds improvements are made all at once.
It also reminds me of how genetic algorithms that I've written tend to work - lots of "no improvement, cull, no improvement, cull" followed by "huge improvement".
It would give the impression, during those bursts, that you're just around the corner from a wildly different world.
There have been a couple efforts I know of to “quantify” science progress in general. In one study[0], physicists, chemists and medical researchers were asked to rate the important of different Nobel-prize-winning discoveries in their field since the prize was established. The results generally showed that discoveries are getting harder to make, where “harder” is indicated by the age of the discoverer and the number of participants in the process.
One important factor that I feel like is overlooked here is that some discoveries are less likely to be appreciated immediately, largely because their impact is not yet fully felt. Also some form of anti-recency bias may be at play here, in that new results that are still somewhat under debate are less likely to be deemed “important” than older, established discoveries.
"It does seem as if there are periods of time in which we make steady progress, and once in a while leaps and bounds improvements are made all at once."
You might be interested in Thomas Khun's[1] famous work: "The Structure of Scientific Revolutions".[2]
I can't imagine the frame of mind wherein when i'm told that there is a way to stave off dying (a gross over-simplification of the article) -- our number one problem for the entirety of our existence -- and I am compelled to sour the news with a reverse "I wish they were dead" statement about my political enemies.
Defeating death just feels larger than human politics, it reaches into the entirety of biology unlike who The Favorite Person is at the moment.
Well then you have weak imagination. No large dictator went out willingly, all who killed tens of millions thought they are on some holy mission for greater good and just squashing the enemies of this greater good.
Death is great, frees up limited resources, removes old farts who think they know how future for everybody should look like without actually having a good reason why.
Lets expand reasonably at least around out solar system first (meaning say >50% of human population not on earth), and then start looming into immortality.
Show me 1 truly powerful person in the past who wasnt an arrogant self centered a-hole.
We talk about enslavement of whole human race potentially forever in worst possible case. If that is something you can ignore, well I can't.
>>> Show me one truly powerful person who could have survived 30% of his subjects actively resisting.
>> Syria is at 40% opposition, 40% pro-government, and Assad has been hanging on during an active civil war for 11 years:
> This illustrates my point
How so? The implication of your GGP comment was that any powerful person with that much opposition should not be able to survive, but the example shows a powerful person with more opposition surviving.
>>> Show me one truly powerful person who could have survived 30% of his subjects actively resisting.
>> It's a lot easier for "truly powerful person" to keep "his subjects [from] actively resisting" than you seem to think.
> Depends completely on the people.
Not really, unless you have a fictitious people that isn't subject to social coordination problems.
However, real populations are subject to those problems, which is why we've seen dynasties of awful dictators survive for generations (e.g. North Korea). The lesson of those dynasties is also probably "don't let up on the oppression or you'll lose power," which might be easier to keep up if the immortal leader doesn't doesn't have to be replaced by a naive successor.
> You have a mental virus that wants to believe everything is doomed.
LOL. Comments like that are totally unpersuasive, and also against the rules.
Well, you do. Lots of people do. I’ve never seen one become self aware though. But anyway, no, not all people are the same. Some populations of people create, initiate, prop up and then perpetuate evil cults of dogma as is the case with North Korea. Some populations never even let it get to step one. Make no mistake, the waves of political dogma lap on every shore. It’s always ready to take over. Some populations are less inclined to group think, save the children and etc. because that’s always what fuels it. I have read a couple of books about North Korea and you can believe me that North Korea was not held at gunpoint to create the regime. I also read “nothing to envy” which is a collection of memoirs written by defectors. They absolutely do it to themselves. And the multi-generational lifespan of that regime makes your point rather moot.
And Assad illustrates my point because I was watching the Syrian civil war and he very nearly did not survive. He was relegated to a bunker and when he emerged he was clearly deeply shaken and a different man. That 40 percent gave him his full moneys worth. To say that this is an example of dictators being invulnerable to dissent is incorrect. If it were 50 or 60 the scale would have tipped. It is an example of my point.
Putin and Trump are not political enemies though, they are criminals. No dietary supplement can offset the premature deaths caused by Putin in Ukraine.
Wow... I'm not equally blaming the Ukrainian president as he is not equally guilty. This is a fact morally (attacking is worse than defending) as well as practically (surrendering would not stop Putin from killing).
And what was Zelenskyi's crime again? Putin's is genocide.
I'm also not defending Putin, but simply as a matter of killing people, Ukraine has the power to prevent that by not fighting, even if it comes at the cost of losing their existence as a country separate from Russia. That could certainly be a bad thing in other ways, but you expressed concern for people killed in the war, not grander moral rights and wrongs.
I don't know if you're missing facts about what is happening in Ukraine, or if you don't see how those events fit the concept of genocide. In short: what is happening in Ukraine is not a normal war.
Putin says his motive is to protect Russian-speakers, create a Russian empire of a single ethnicity and "undo" Ukraine as a nation. He dehumanizes Ukrainians. He removes the Ukrainian language from the areas he captures such as Donbas. He has abducted hundreds of Ukrainian children. While he "protects" Russian speakers, he commands his troops to kill Ukrainian civilians in masses.
I'm not sure if you realize, but you are getting a highly framed version of events.
Just be aware how biased your sources are. Imagine if Canada decided to get out of NATO to join up with China. Overthrew a pro US friendly democratic government. Chinese BioLabs started popping up all over. Made it public that they want Chinese missiles within firing rang of US cities. And ethnic cleansing of US citizens was going on for a few years. Judging by the "Shock and Awe" strategy employed on Iraq, I don't think America would be anywhere near as constrained under same circumstances. My bet is they America would bomb the shit out of Canada. Putin has been somewhat restrained, willing to sacrifice the lives of tens of thousands of his soldiers to spare the cities from bombing.
This is not a pro Russia post. More like "War is a Racket" and there are people that want to prolong this conflict. And it goes deeper than that. Ever since Putin imprisoned some US connected oligarchs, the US strategy has been to get rid of Putin. This war is culminating result of years of wrong headed US foreign policy. "Wrong headed" in the sense that Russians will not become some economic neo-colonial state of the West.
In addition to Trump Derangement Syndrome there is also a Democrat Derangement Syndrome, and many others. Tribalistic news feeds tempt many of our brains into seeing all of life along these lines. Even food ican be political
My point was more that someone saying "even a vampire got bored" is less than helpful, as they're using a literally fictional character as their example.
It's like saying "even the tooth fairy got bored".
Aging is quite a sad prospect overall, but as long as everyone is subject to the same process it is a great equalizer of sorts. An unforeseen consequence that is often brought up regarding the philosophy of unlimited or greatly extended human age is that it would exacerbate all inequalities in a society. As it’s well-known, time is the biggest pyramid scheme of them all.
On the day of Tiananmen massacre, it occurred to me that it would have even stronger repercussions at country scale.
Taking democratic countries’ shift to the policy of non-involvement and combining it with hypothetical advancements that continuously extend Supreme Leaders’ ages essentially sentences generations of dictatorships’ subjects to hardship, exploitation and gaslit life under a kleptocracy.
Add to that increased existential threat to democracy, since such a dictator never would have to deal with inefficiencies of internal power and knowledge transfer or spending resources on facilitating an honest voting process, infinitely building connections and spinning its webs around the remaining parts of the free world.
One wicked old man interminably learning new ways to turn the world into a zero-sum game and win at it, as generations of servants come and go around him they are even easier to control.
Yea I think of the Elves in Lord of the Rings. If a person has lived 200 years then they have lived long enough to see and understand the true costs of war.
That’s like saying that one person will dominate the tv show survivor. In reality new cliques and alliances form all the time, power shifts and swirls as alliances coalesce and disperse. We will still have wars and disasters and things that no one person can control. Plus, people will still die just not necessarily from the disease of aging. I often notice that people resist something they are afraid of by thinking it will cause a disaster to change how things are. I think you are subconsciously afraid that it’s too good to be true. In reality it will be like penicillin or vaccines — massive improvement and not much else.
You may be thinking that this tech will automatically trickle down. There is infinite incentive to withhold it, whether by controlling access to it outright in a dictatorship or by letting it naturally be exorbitantly expensive in a market economy.
Note that in thought experiments I mentioned it is considered to exacerbate inequalities even if it is distributed equally to all. A thought experiment that reflects reality a bit better would be one where the rich not only get more rich thanks to money dynamics (plus a vicious circle of theft and violence in case of dictators, who are the bigger concern) but also never die.
> There are precisely zero things that were deliberately made to be more expensive than their intrinsic cost by a small group of “rich people and dictators”
Setting aside the fact that 0) US healthcare is pretty much all “things being made more expensive than their intrinsic cost”, believing 1) the market in a democracy is not affected by information asymmetry and 2) a dictator-kleptocrat elsewhere even needs to manipulate prices hints at immense naivety on your part.
> shut up
If it’s my mention of the June 4th incident that triggered such reaction, I hope the Party pays you well enough to justify the stress that reading Western media must be to you.
> you have no right to pose as some kind of intellectual
And you have clearly run out of substance to present.
Surprised to see this take from you. We could also have your parents, grandparents, siblings, kids, grandkids not get sick and suffer terribly before being discarded like garbage. And we can keep all the amazing people who fight for good. Oh wait, that would mean we can’t stick it to some bad people, never mind.
> Surprised to see this take from you. We could also have your parents, grandparents, siblings, kids, grandkids not get sick and suffer terribly before being discarded like garbage. And we can keep all the amazing people who fight for good. Oh wait, that would mean we can’t stick it to some bad people, never mind.
I don't think you're thinking this through. Immortality plus "kids, grandkids" (without sci-fi spaceships or suicide/euthanasia) will pretty quickly lead to overpopulation and a lot of obvious problems.
If it leads to decades more time of fertile reproduction and productivity, it needn't do so. We'll still have some rapid diseases not related to age, and of course accidents. If some of our brightest minds have another 40 years at the peak of their scientific and engineering careers, maybe we'll have seasteading and urban hydronic/aquaponic/aeroponic food supplies figured out and affordable. Convincing people not to have another generation at 20 years of age would of course be the hard part.
Let’s establish the fact. Nobody knows what the consequences will be. But overpopulation won’t be The outcome. Developed countries have a population die-off problem. In the US the birth rate has plummeted since the 70s and we are way below replacement. We desperately need more people.
Tens of thousands of people die in car accidents alone every year. The geriatric population is exploding and we can’t take care of all of them. We need a cure for the disease of aging.
So you're solving the overpopulation problem by hoping the "kids, grandkids" don't exist or are small enough in number that death via accidents creates the space for them. OK.
The corollary of immortality for everyone (without sci-fi spaceships or suicide/euthanasia) is either stagnation (more or less the same set of people existing until resources run out) or overpopulation (and prompt resource exhaustion).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428053/pdf/nih...