5 ms·

Researchers Claim Serum Albumin Increases Mouse Lifespan

60 points by lelf 4y ago

Supermancho 4y ago
One hospital's guidelines for the use of Albumin - https://www.universityhealthsystem.com/~/media/files/clinical-pathways/albumin-guidelines-0410.pdf https://www.universityhealthsystem.com/~/media/files/clinica... Note the reference to the Cochrane collaboration review as a trusted source. Some HN'ers have expressed unfamiliarity with this organization.
ramraj07 4y ago
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.
- inglor_cz 4y ago
  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?
  - ramraj07 4y ago
    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.
    - inglor_cz 4y ago
      It is something that emerged in the longevity subreddit some time ago.
      - netizen-936824 4y ago
        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
        inglor_cz 4y ago
        Specifically albumin, which surprised me a bit back then, but admittedly I do not know nearly enough about proteins to be validly surprised.
- icoder 4y ago
  Peter Thiel or Peter Attia?
  - ramraj07 4y ago
    The former allegedly injects himself with young people blood so him.
    - kikoreis 4y ago
      Yes? No? Maybe? - https://www.vanityfair.com/news/2016/08/peter-thiel-wants-to-inject-himself-with-young-peoples-blood https://www.vanityfair.com/news/2016/08/peter-thiel-wants-to... - https://techcrunch.com/2017/06/14/no-peter-thiel-is-not-harvesting-the-blood-of-the-young/ https://techcrunch.com/2017/06/14/no-peter-thiel-is-not-harv... - https://gizmodo.com/someone-is-trying-to-discredit-the-story-of-peter-thiel-1796135794 https://gizmodo.com/someone-is-trying-to-discredit-the-story... - https://www.independent.co.uk/tech/peter-thiel-vampire-donald-trump-life-extension-blood-transfusion-ambrosia-palantir-a8614061.html https://www.independent.co.uk/tech/peter-thiel-vampire-donal...
      - ramraj07 4y ago
        And that’s why I used the word allegedly.
godelski 4y ago
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?
- ramraj07 4y ago
  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.
- Terry_Roll 4y ago
  > As a minor question, we see these studies a lot in mice. Are they being followed up in other animals and humans? Yeah, lots of aging studies exist. https://joshmitteldorf.scienceblog.com/2017/02/06/glycine-and-mitochondria/ https://joshmitteldorf.scienceblog.com/2017/02/06/glycine-an... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/ "Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults" 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!
deleted 4y ago
[deleted]
snvzz 4y ago
Refer to SENS foundation for actual serious research on reversing aging[0]. 0. https://www.sens.org/our-research/intro-to-sens-research/ https://www.sens.org/our-research/intro-to-sens-research/
inglor_cz 4y ago
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.
DoreenMichele 4y ago
Without the presence of albumin, the high pressure of the blood vessels would push more fluids into the tissues. Sounds to me like this would have significant implications for the ability of the body to return interstitial fluid to the bloodstream efficiently.
- adrian_b 4y ago
  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.
  - DoreenMichele 4y ago
    Thank you. 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.
Khelavaster 4y ago
Serum albumin transports thyroid hormone, which regulates energy-consumption processes.
robwwilliams 4y ago
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 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.

60 points by lelf 4y ago

One hospital's guidelines for the use of Albumin - https://www.universityhealthsystem.com/~/media/files/clinical-pathways/albumin-guidelines-0410.pdf https://www.universityhealthsystem.com/~/media/files/clinica... Note the reference to the Cochrane collaboration review as a trusted source. Some HN'ers have expressed unfamiliarity with this organization.

ramraj07 4y ago

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.

inglor_cz 4y ago
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?
- ramraj07 4y ago
  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.
  - inglor_cz 4y ago
    It is something that emerged in the longevity subreddit some time ago.
    - netizen-936824 4y ago
      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
      - inglor_cz 4y ago
        Specifically albumin, which surprised me a bit back then, but admittedly I do not know nearly enough about proteins to be validly surprised.
icoder 4y ago
Peter Thiel or Peter Attia?
- ramraj07 4y ago
  The former allegedly injects himself with young people blood so him.
  - kikoreis 4y ago
    Yes? No? Maybe? - https://www.vanityfair.com/news/2016/08/peter-thiel-wants-to-inject-himself-with-young-peoples-blood https://www.vanityfair.com/news/2016/08/peter-thiel-wants-to... - https://techcrunch.com/2017/06/14/no-peter-thiel-is-not-harvesting-the-blood-of-the-young/ https://techcrunch.com/2017/06/14/no-peter-thiel-is-not-harv... - https://gizmodo.com/someone-is-trying-to-discredit-the-story-of-peter-thiel-1796135794 https://gizmodo.com/someone-is-trying-to-discredit-the-story... - https://www.independent.co.uk/tech/peter-thiel-vampire-donald-trump-life-extension-blood-transfusion-ambrosia-palantir-a8614061.html https://www.independent.co.uk/tech/peter-thiel-vampire-donal...
    - ramraj07 4y ago
      And that’s why I used the word allegedly.

godelski 4y ago

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?

ramraj07 4y ago
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.
Terry_Roll 4y ago
> As a minor question, we see these studies a lot in mice. Are they being followed up in other animals and humans? Yeah, lots of aging studies exist. https://joshmitteldorf.scienceblog.com/2017/02/06/glycine-and-mitochondria/ https://joshmitteldorf.scienceblog.com/2017/02/06/glycine-an... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002905/ "Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults" 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!

deleted 4y ago

[deleted]

snvzz 4y ago

Refer to SENS foundation for actual serious research on reversing aging[0]. 0. https://www.sens.org/our-research/intro-to-sens-research/ https://www.sens.org/our-research/intro-to-sens-research/

inglor_cz 4y ago

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.

DoreenMichele 4y ago

Without the presence of albumin, the high pressure of the blood vessels would push more fluids into the tissues. Sounds to me like this would have significant implications for the ability of the body to return interstitial fluid to the bloodstream efficiently.

adrian_b 4y ago
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.
- DoreenMichele 4y ago
  Thank you. 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.

Khelavaster 4y ago

Serum albumin transports thyroid hormone, which regulates energy-consumption processes.

robwwilliams 4y ago

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 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.