Not a doctor, but a PhD with some work on protein pharmacokinetics. Serum albumin and antibodies are the two longest lived proteins in your blood because we have special mechanisms and proteins to salvage them from where other proteins get degraded. That’s why their half life in blood is in months. They’re also (unless you make them targeted) benign in many ways (hence IVIG is used fairly indiscriminately). Thus, of all the longevity related therapy ideas, this seems the most benign. And makes a little bit of sense too, though further mechanism studies are needed (which are always hard).
If Peter Thiel or some other longevity obsessed techidiot is reading this though, don’t go around injecting albumin into yourself yet - and don’t talk to quack doctors obsessed with longevity either. What I’ve learned time and again is you always think Ying and your body’s biology will come and Yang you in the kidney.
Seeing an expert here, I have a question. What about misfolded albumin, is that a (significant) thing? Does the fraction of misfolded albumin increase significantly with aging?
I did a quick google since I’ve never heard of misfolded albumin in the serum before and didn’t find anything.. are you asking from any prior research or discussions? Just from my knowledge I’d be surprised if there’s any amount of misfolded protein in the blood stream - every protein molecule in the blood stream needs to be actively salvaged (in your kidneys and macrophages) from degradation and this salvation is provided through their binding to receptors. If albumin is misfolded it should be cleared out quite fast. Note this is why antibody based drugs are more popular now - you get month long half lives for free.
Were those discussions about proteins in general misfolding or specifically serum albumin? This is an important distinction, many conversations I've overheard from those not in a bio field seem to gloss over vital details
It seems every few months we find something new that increases lifespan in mice 10-20% (17-20% in this study). They appear to be different chemicals or treatments. So I have two big questions here.
1) Obviously aging is a multifaceted problem, are there metastudies studying the interactions? This clearly needs to be done as people are assuming increased longevity in mice equates to increased longevity in humans are are self administering these treatments prior to human trials.
2) How can independent treatments through independent mechanisms cause such similar (and quite large) increases in lifespans? Is mice biology just far simpler? Am I misunderstanding the independence? Is this low sampling causing biases or some other statistical phenomena? Is there bad faith and people reporting the research (or the researchers themselves) overstating the value of these treatments? Are these treatments just making mice live closer to their natural lifespans but just being better able to adapt to an environment not optimized for their biology? (I know not all labs use warm and mice optimized environments, though my understanding is most do)
As a minor question, we see these studies a lot in mice. Are they being followed up in other animals and humans? We never hear about followups on HN and so that makes me pretty skeptical. Mice aren't humans. There's a lot of people interested in longevity research. I know there's a lot of money being put into it. How do we distinguish hype from reality?
I have many examples of the above, in the UK the NHS stance is to give everyone and anyone who is elderly in a care home a b12 shot when possible, which is just a form of cobalt, but that assumes they have enough cysteine!
I remember some quote around here on how future alien civilizations discovering the ruins of ours would be astonished to see how much effort we had devoted to extend the lifespan of mice.
Longevity pathways are fairly conserved throughout animal kingdom. Genes that cause worms to live really long also seem to be involved in longevity in mammals. Many triggers in your metabolism can all funnel down to the same signaling pathways (in this case likely mToR) and hence you see so many stimuli possibilities.
Not a solid study for at least five distinct reasons:
1. The lifespan of both control and treated mice (C57BL/6N) is very significantly less than all other studies of which I am aware. See for example: https://phenome.jax.org/measures/23201
by Yuan et al. In this study untreated B6 untreated B6 mice typically have a median lifespan of over 800+ days.
2. The phenotyping of animals was apparently not done blinded to treatment. This can introduce strong bias in data generation.
3. No completely untreated control. For all we know the iv injection every three weeks contributed to short lifespan snd perhaps albumin mitigated stress response.
4. No control for injection of other major serum proteins such as gelsolin. What evidence demonstrates selectivity of albumin? None.
5. This is again a study of a single inbred genome of mouse. N=1. While both sexes were studied, it would be great to see results replicated properly using genetically diverse UM-HET3 mice.
That is rather remarkable, because mice are very prone to cancer. Much more so than humans. I have heard longevity experts remarking that even interventions that could actually significantly raise lifespans of other species are going to run into the wall of enormous cancer-ness of mice, which reduces the overall effect.
Usually the first signs of having too low albumin in the blood (due to either eating too little protein or insufficient albumin synthesis in the liver or bad digestion of proteins or malabsorbtion of aminoacids in the intestine) are bilateral oedema of the legs, i.e. large swellings of the feet and lower legs, which become very large and spongy.
With even lower albumin in the blood, the pressure becomes so large that the lymph (i.e. the water) begins to exit the legs through the skin and the condition can become life-threatening, so the low albumin must be corrected by providing intravenous albumin and the primary cause for having low albumin must be treated.
I have seen all these symptoms when my mother had for a few months malabsorbtion in the intestine following some difficult surgery and a time of intensive care and IV feeding. Discovering the precise cause of the low albumin in blood was quite difficult, but it was important. The medical doctors who treated her would have been happy to just give her permanently IV albumin, until death, but this was not really a sustainable option (both due to high cost and because it would have tied her to a bed for a large part of the time), so the real cause of the low albumin had to be identified and corrected.
Too high albumin in the blood would have the opposite effect, by extracting the water from the tissues into the blood vessels. Presumably, if external albumin is added as in this experiment, the liver will diminish a lot its albumin synthesis activity, to keep the right amount of albumin in circulation. This might also have some influence over the lifespan, not only the existence of supposedly better, young albumin in the blood.
I would be interested in hearing more about what was done to correct the issue or any other tidbits you might know about improving albumin production. I have chronic edema from an incurable condition.
I could not identify precisely the cause of low albumin in my mother, but the blood and urine analyses were consistent with normal hepatic and renal functions, i.e. neither aminoacids nor proteins were eliminated by the kidneys and there seemed to be no reason why the liver should not be able to synthesize albumin.
That leaved as the most probable causes either bad digestion of proteins or malabsorbtion of the aminoacids in the intestine, the latter being more probable, due to the nature of her previous medical problems.
So I have just conceived a special diet for her, very rich in diverse protein sources, and I have also given her some digestive aids with enzymes, to cover the case when there would have been some gastric or pancreatic problem in the secretion of digestive enzymes.
The improvements have been very slow, as she was in her eighties and recovering after a severe surgery, but with the very rich in protein diet the albumin levels eventually recovered and after a few months she could go back to a normal diet.
Fortunately this was a temporary condition, due to previous intestinal damage, which slowly healed, and not some permanent problem, for which it might have been difficult to find a cure.
The main difficulties were caused by the various opinions of the consulted doctors, none of which were helpful in finding the common-sense solution, which worked.
When either too little protein enters the body due to defects in the digestive system, or too much protein exits the body, due to defects in the excretory system, there are some chances to alleviate the condition by eating more proteins.
When the defects are in the liver ability of protein synthesis, that is much harder to overcome.
Like I have said, besides tablets with digestive enzymes, the special diet included generous quantities of protein-rich ingredients, e.g. lentils or other legumes, turkey breast or chicken breast or turkey thighs (turkey thighs, which have low fat, were included among the options because she preferred their taste), as much chicken liver as it would not cause the daily vitamin A intake to approach the maximum acceptable level (turkey liver cannot substitute chicken liver, because it contains too much vitamin A), egg white, and, because she liked dairy very much, yogurt and several kinds of cheese, preferably kinds with much protein and little fat, e.g. whey cheese, like ricotta.
If Peter Thiel or some other longevity obsessed techidiot is reading this though, don’t go around injecting albumin into yourself yet - and don’t talk to quack doctors obsessed with longevity either. What I’ve learned time and again is you always think Ying and your body’s biology will come and Yang you in the kidney.