5 ms·

In mice, of course. What are the broader implications of this supposed to be?

thornjm 4y ago
Fatty liver and high fat in blood is a disease and a risk factor for serious disease respectively. This study appears to show that fasting is related to inducing the gene Slc25a51 and improving those factors. I guess this contributes to the body of science around the potential health benefits of fasting.
- mistrial9 4y ago
  ok - but the purpose of publicly identifying by name, a particular genetic component, is to own that function commercially somehow - am i wrong?
  - SargeZT 4y ago
    Eventually it may be a contributor to a commercialization, but now it makes it a target for research for others. This isn't patenting anything, it's scientists saying 'this is an important bit when it comes to the effects of fasting so let's focus on this.' What would be scummy would be some pharmaceutical company discovering this, not releasing the information, and trying to develop (or worse, failing to develop) a drug on their own after internal research that was never released to the world.
aydyn 4y ago
Mice are physiologically small humans with tails and fur. Findings in mice are very relevant to humans.
- jjallen 4y ago
  I’ve always wondered what percentage of mice (and other non human animal) findings turned out to be applicable to humans as well. Anyone have an idea?
  - throwawaymaths 4y ago
    Not confident on diabetes. The biophysical dynamics of insulin are super different in mice - they have two, one of which is missing a highly conserved amino acid across all vertebrates that is at the hinge of the critical structural element of insulin. https://www.frontiersin.org/articles/10.3389/fendo.2021.649255/full https://www.frontiersin.org/articles/10.3389/fendo.2021.6492... Literally no one talks about this in mice metabolic research. I would not be surprised if a huge majority of mouse researchers in diabetes are unaware.
    - mnw21cam 4y ago
      I work in human diabetes genetics. We're just publishing work on a gene that doesn't even exist in mice - https://www.medrxiv.org/content/10.1101/2021.08.23.21262262v1 https://www.medrxiv.org/content/10.1101/2021.08.23.21262262v... Part of our message is basically what you just said. We have multiple examples of genes where mutations cause diabetes in humans but don't in mice. The other one we have is the fact that human pancreatic beta cell lines in labs don't even 100% act like human pancreatic beta cells in humans.
  - tsol 4y ago
    >The first thing to note is of those drugs which pass animal tests, 94% will fail during human clinical trials stages (Phases 1 – 3)*. https://www.understandinganimalresearch.org.uk/news/nine-out-of-ten-statistics-are-taken-out-of-context https://www.understandinganimalresearch.org.uk/news/nine-out... But to be fair, there's a huge failure rate for pharmaceutical drugs in general.
- Symmetry 4y ago
  For many things yes. But humans have been under much more intense selective pressure for longer lifespans so easy interventions along those lines that work in mice have a history of not panning out in humans.
alwillis 4y ago
One possibly obvious one: Fasting in mice turns on SIRT3 which requires NAD+ and this newly discovered gene SLC25A51 is involved in transporting NAD+ to SIRT3. There's plenty of data that shows mice can live 30% longer when calorie-restricted due to sirtuins being activated.. Anyone who's ever listed to Dr. David Sinclair speak about longevity, he almost always talks about how NAD+ is possibly the most important chemical in the human body, since we'd be "dead in 30 seconds" without it. Sirtuins are the longevity genes that are activated when organisms are under duress, which can be simulated by fasting. Your body doesn't know when you're going to eat again, so the sirtuins get activated. I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting. You can listen to David Sinclair and Rhonda Patrick get into the details of how all of this works: https://www.foundmyfitness.com/episodes/david-sinclair https://www.foundmyfitness.com/episodes/david-sinclair
- ChrstnBonanno 4y ago
  Polymorphisms in SLC25A51 might be linked to chronic fatigue or other mitochondria disorders. So that is pretty important. Sinclair, IMHO, is all protein and zero enzyme and that is his problem. Without enough zinc NMNAT will not function and will slow the SIRT cycle. And increasing SIRT activity by shoving NAD in the cell with out zinc will end up depleting zinc.
- TedDoesntTalk 4y ago
  Rhonda Patrick is amazing. Been a subscriber to her posts podcast for 3 years. But she has tons of free content on YouTube and elsewhere. It was disappointing to hear David Sinclair makes his own resveratrol… can’t get it
- deleted 4y ago
  [deleted]
- rsync 4y ago
  "I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting." To what end ? Fasting would be cheaper, easier and less time-consuming and would include all of the related, broad-spectrum effects that we also believe fasting may produce. I guess if you're a pharma investor or existing, entrenched player it makes sense to go that direction. As a consumer, however, I wonder why (pills that might convey a subset of the benefits of fasting) would be interesting in any way.
caeril 4y ago
Why does this tired argument always appear on HN? We share 97% of our genes with mice. Our organ systems and metabolic pathways are extremely similar. Our homeostatic mechanisms are nearly identical. Some mouse models don't carry over to us, to be sure. But the reality is that most do. Do we know for a fact that this paper applies to us? No. But it significantly updates our priors. And that's always noteworthy.
- d0mine 4y ago
  9 out 10 results in mice do not transfer to humans. For example, fasting for several hours in mice and in humans are completely different things (a human would have to fast for days to get similar results).

Fatty liver and high fat in blood is a disease and a risk factor for serious disease respectively. This study appears to show that fasting is related to inducing the gene Slc25a51 and improving those factors. I guess this contributes to the body of science around the potential health benefits of fasting.

mistrial9 4y ago
ok - but the purpose of publicly identifying by name, a particular genetic component, is to own that function commercially somehow - am i wrong?
- SargeZT 4y ago
  Eventually it may be a contributor to a commercialization, but now it makes it a target for research for others. This isn't patenting anything, it's scientists saying 'this is an important bit when it comes to the effects of fasting so let's focus on this.' What would be scummy would be some pharmaceutical company discovering this, not releasing the information, and trying to develop (or worse, failing to develop) a drug on their own after internal research that was never released to the world.

aydyn 4y ago

Mice are physiologically small humans with tails and fur. Findings in mice are very relevant to humans.

jjallen 4y ago
I’ve always wondered what percentage of mice (and other non human animal) findings turned out to be applicable to humans as well. Anyone have an idea?
- throwawaymaths 4y ago
  Not confident on diabetes. The biophysical dynamics of insulin are super different in mice - they have two, one of which is missing a highly conserved amino acid across all vertebrates that is at the hinge of the critical structural element of insulin. https://www.frontiersin.org/articles/10.3389/fendo.2021.649255/full https://www.frontiersin.org/articles/10.3389/fendo.2021.6492... Literally no one talks about this in mice metabolic research. I would not be surprised if a huge majority of mouse researchers in diabetes are unaware.
  - mnw21cam 4y ago
    I work in human diabetes genetics. We're just publishing work on a gene that doesn't even exist in mice - https://www.medrxiv.org/content/10.1101/2021.08.23.21262262v1 https://www.medrxiv.org/content/10.1101/2021.08.23.21262262v... Part of our message is basically what you just said. We have multiple examples of genes where mutations cause diabetes in humans but don't in mice. The other one we have is the fact that human pancreatic beta cell lines in labs don't even 100% act like human pancreatic beta cells in humans.
- tsol 4y ago
  >The first thing to note is of those drugs which pass animal tests, 94% will fail during human clinical trials stages (Phases 1 – 3)*. https://www.understandinganimalresearch.org.uk/news/nine-out-of-ten-statistics-are-taken-out-of-context https://www.understandinganimalresearch.org.uk/news/nine-out... But to be fair, there's a huge failure rate for pharmaceutical drugs in general.
Symmetry 4y ago
For many things yes. But humans have been under much more intense selective pressure for longer lifespans so easy interventions along those lines that work in mice have a history of not panning out in humans.

alwillis 4y ago

One possibly obvious one: Fasting in mice turns on SIRT3 which requires NAD+ and this newly discovered gene SLC25A51 is involved in transporting NAD+ to SIRT3. There's plenty of data that shows mice can live 30% longer when calorie-restricted due to sirtuins being activated.. Anyone who's ever listed to Dr. David Sinclair speak about longevity, he almost always talks about how NAD+ is possibly the most important chemical in the human body, since we'd be "dead in 30 seconds" without it. Sirtuins are the longevity genes that are activated when organisms are under duress, which can be simulated by fasting. Your body doesn't know when you're going to eat again, so the sirtuins get activated. I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting. You can listen to David Sinclair and Rhonda Patrick get into the details of how all of this works: https://www.foundmyfitness.com/episodes/david-sinclair https://www.foundmyfitness.com/episodes/david-sinclair

ChrstnBonanno 4y ago
Polymorphisms in SLC25A51 might be linked to chronic fatigue or other mitochondria disorders. So that is pretty important. Sinclair, IMHO, is all protein and zero enzyme and that is his problem. Without enough zinc NMNAT will not function and will slow the SIRT cycle. And increasing SIRT activity by shoving NAD in the cell with out zinc will end up depleting zinc.
TedDoesntTalk 4y ago
Rhonda Patrick is amazing. Been a subscriber to her posts podcast for 3 years. But she has tons of free content on YouTube and elsewhere. It was disappointing to hear David Sinclair makes his own resveratrol… can’t get it
deleted 4y ago
[deleted]
rsync 4y ago
"I wouldn't be surprised if researchers and labs are looking for ways to activate SLC25A51 chemically to get the NAD+ flowing to SIRT3 without requiring fasting." To what end ? Fasting would be cheaper, easier and less time-consuming and would include all of the related, broad-spectrum effects that we also believe fasting may produce. I guess if you're a pharma investor or existing, entrenched player it makes sense to go that direction. As a consumer, however, I wonder why (pills that might convey a subset of the benefits of fasting) would be interesting in any way.

caeril 4y ago

Why does this tired argument always appear on HN? We share 97% of our genes with mice. Our organ systems and metabolic pathways are extremely similar. Our homeostatic mechanisms are nearly identical. Some mouse models don't carry over to us, to be sure. But the reality is that most do. Do we know for a fact that this paper applies to us? No. But it significantly updates our priors. And that's always noteworthy.

d0mine 4y ago
9 out 10 results in mice do not transfer to humans. For example, fasting for several hours in mice and in humans are completely different things (a human would have to fast for days to get similar results).