Scientists Discover Ways of Making Old Blood New Again
news.cuanschutz.edu
news.cuanschutz.edu
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428053/pdf/nih...
There are references to them using “5-fluorouracil (5FU)”, which appears to be a chemotherapy drug.
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.
[0]https://www.sciencedirect.com/science/article/pii/S156816371...
>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.
[0]https://www.mdpi.com/1422-0067/18/9/1865/htm
[1]https://www.sciencedirect.com/science/article/pii/S096800042...
[2]https://www.tandfonline.com/doi/full/10.1080/15548627.2019.1...
If you want to DIY it... Donate blood often :)
If Hackernews taught me anything, it's that diet is the root cause for all major illness, and fasting is the cure.
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.
The best summary I've seen is this: https://spyderdoc.substack.com/p/doctors-heart-series-part-6...
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.
I also have this link saved for some reason: https://www.sciencedirect.com/science/article/pii/S155041311...
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.
Giving blood isn't really a big deal for a healthy person.
For my friend it's just anecdata with n=1
"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."
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2222....
From https://www.livestrong.com/article/490323-foods-high-in-gamm...
How can one person have 60 daily sessions?
math checks out
Chief issue of autoimmune issues is inflammation. AIP diet focuses on foods that reduce inflammation.
Many (not all!) people in support forums find signifiant relief from following AIP.
It is similar to Keto.
It's far easier to consistently access decent organic produce everywhere I tend to live.
Still, there's so much progress being made in health stuff generally. Makes me optimistic about my older years.
Grow black mice that are hyperresponsive and white mice that are hyporesponsive (?) while optimizing for minimum genetic distance.
Sell them in equally weighted batches as yin/yang mice ("purely for esthetic reasons, also suitable for lab tests")
For me it looks too easy to have a successful experiment (and article) if you can choose how you poison the animal.
I have always wondered why they did not use a commercial model, and better tested their hypothesis on several, unrelated animal models.
--- 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."
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.
You might be interested in Thomas Khun's[1] famous work: "The Structure of Scientific Revolutions".[2]
[1] - https://en.wikipedia.org/wiki/Thomas_Kuhn
[2] - https://en.wikipedia.org/wiki/The_Structure_of_Scientific_Re...
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.
0: https://www.theatlantic.com/science/archive/2018/11/diminish...
Defeating death just feels larger than human politics, it reaches into the entirety of biology unlike who The Favorite Person is at the moment.
Is it though? Who wants to live forever? Even Lestat got bored.
You mean the fictional vampire character?
It's like saying "even the tooth fairy got bored".
I don't think either of these are recognized by the DSM-5.
Putin and Trump are not political enemies though, they are criminals. No dietary supplement can offset the premature deaths caused by Putin in Ukraine.
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.
It's a lot easier for "truly powerful person" to keep "his subjects [from] actively resisting" than you seem to think.
>> 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.
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.
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.
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.
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.
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).