8 ms·

Elusive mitochondrial connection to inflammation uncovered

242 points by dtawfik1 8y ago

fsnarskiy 8y ago
This is actually very interesting. Low-grade inflammation is often linked to aging and cancer developments, it is however often unclear whether its cause/effect or correlation - https://academic.oup.com/biomedgerontology/article/69/Suppl_1/S4/587037 https://academic.oup.com/biomedgerontology/article/69/Suppl_... But mechanisms of inflammation are many and still pretty illusive, this is a great step towards understanding aging mechanisms in general.
- deleted 8y ago
  [deleted]
jgalvez 8y ago
Ray Peat anyone? :)
- asdfasdfdavid 8y ago
  Absolutely, nobody knows better how to take care of our mitochondria than Ray Peat.
reasonattlm 8y ago
Oxidative stress and inflammation go hand in hand. Aging has rising levels of both. Mitochondrially targeted antioxidants such as SkQ1 were first approved for use against inflammatory eye conditions. They act to dampen the consequences / amount of inflammation, and do this by cutting down on oxidizing molecules produced within mitochondria. They were first developed out of an interest to slow aging through this sort of modulation of mitochondrial oxidative stress and damage. They do slow aging to some degree, but don't do anywhere near as well as calorie restriction - say 10% in flies, something less than that in mice, which isn't impressive. The first earnest human trials for mitochondrially targeted antioxidants such as MitoQ (which from the studies is actually less effective than SkQ1) suggest it can reduce the impact of oxidative stress or inflammation on the smooth muscle cells in blood vessel walls. Their dysfunction produces some fraction of the stiffening of blood vessels with age. That stiffening causes raised blood pressure, which in turn causes too many bad things to list here. So these are not massive effects. You can probably do as well as MitoQ by bumping up your exercise level to the next tier. But then you can always both exercise and take a mitochondrially targeted antioxidant. The costs are not high, so it may be worth it based on the preliminary data. Not a cure for aging, and thus not worth spilling immense amounts of ink and effort over it. Just something to think about doing and then get on with better development projects with better expected outcomes.
- SubiculumCode 8y ago
  Then melatonin supplementation might be the way to go.... https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+mitochondrial+stress&hl=en&as_sdt=0,5&as_vis=1 https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+m...
- fasteo 8y ago
  Wow, I did not expect to find you here reason !! mitomutant from Longecity speaking.
0x8BADF00D 8y ago
I wonder why we developed the STING protein in the first place. Was it perhaps an early form of immunity, or a precursor to an immune response?
- maxander 8y ago
  The name stands for STimulator of INterferon Genes, where interferons are essentially message-carrying molecules involved with the immune system. STING protein, I believe, is essentially a detector which gets triggered when a cell is invaded by a virus or encounters a parasite. For that, it still serves an important purpose.
jonmc12 8y ago
If you are interested in more information about Autophagic processes, this video interview is great: https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patrick_brings_nerd_level_video_on/ https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patr... Rhonda Patrick interviews Dr Guido Kroemer, an expert in Autophagy. Its one of the most accessible, well-referenced and thorough discussions on Autophagy (including Mitophagy), that I've come across.
- dpatrick86 8y ago
  Transcript and other resources available here. https://www.foundmyfitness.com/episodes/guido-kroemer https://www.foundmyfitness.com/episodes/guido-kroemer Thanks for sharing!
  - ra 8y ago
    Dr Rhonda Patrick's podcast, Found My Fitness, is excellent.
king_panic 8y ago
2012: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/
MarkThief 8y ago
So this could be what is causing all these nearly undiagnosable cases of autoimmune disease?
wolco 8y ago
This is highly interesting. After taking ciprofloxan 10 months ago I'm still trying to get my damaged mitochondria back in order.
- phkahler 8y ago
  If it affected your tendons Magnesium is recommended. I'd also speculatively suggest iodine (a few mg per day) and glycine (1-20 grams per day). I am not a doctor, but then that's who prescribed you that crap ;-)
  - monotone666 8y ago
    I have chronic fatigue likely brought on by mitochondrial dysfunction. Iodine ended a 12 month long mono infection and is the difference between having enough energy to spend the day reading.
- DoreenMichele 8y ago
  I'm curious what you mean by that. It sounds like an odd way to frame it.
  - wolco 8y ago
    I've personally never struggled so hard to recover from anything. I couldn't do it justice in a short post. Lost 75 pounds in a 45 days. Heartrate over a 100 for a month. Here is a link to another nature article on it: https://www.nature.com/articles/d41586-018-03267-5 https://www.nature.com/articles/d41586-018-03267-5
    - DoreenMichele 8y ago
      Yes, I've recovered from long term prescription drug use. It was awful. I just thought mitochondrial damage was a strange framing. Thanks. Edit: The article does talk about mitochondrial damage, though it didn't appear at first glance to address this. It's towards the end of the article.
- 8y ago
ArtWomb 8y ago
One mental model which may help in visualizing "oxidative stress" in mitochondrial networks is to liken it to a "first-order phase transition" in solid-state physics. Gene expression regulates structure. And structure determines function. But whereas a typical sample of inorganic material may possess a handful of stable states under room temperature conditions. Nuclear genomics in mammals express 1000s of proteins. MIT's Broad Institute has begun compiling a reference atlas: MitoCarta 2.0: An Inventory Of Mammalian Mitochodrial Genes https://www.broadinstitute.org/scientific-community/science/programs/metabolic-disease-program/publications/mitocarta/mitocarta-in-0 https://www.broadinstitute.org/scientific-community/science/...
- narrator 8y ago
  If you could acurately simulate biological systems with a computer model, you could do drug development in the cloud without the need for clinical trials. Unfortunately, protein folding and even predicting whether a molecule will be an agonist at a particular receptor site are very slow algorithms.
  - JunkDNA 8y ago
    Accurately simulating biological systems in the cloud to run a virtual clinical trial is like trying to predict the exact weather for Washington DC at a specific date and time hundreds of years from now using weather forecast models. It’s pretty much impossible with current biomedical knowledge. To simulate humans well enough to eliminate a clinical trial, you would have to simulate every single cell, organ, and organ system as well as the substantial population of bacterial and fungal microorganisms that live on and inside humans (as well as all their unique biology too). Building such a simulation would require a level of knowledge of biology that the human race currently does not possess.
    - dflock 8y ago
      Also, computronium.
    - snaky 8y ago
fasteo 8y ago
Interesting post and comments, as usual. I wanted to give some pragmatic information related to this. I have a genetic condition that makes my mitochondria to malfunction. I was diagnosed about 10 years ago. At first, I started taking supplements to increase the production of ATP, but my "vitality" did not improve much. I could workout normally, but my recovery ability was poor, and from time to time I would just crash and burn for 2-3 days. After much reading, I came to the conclusion that the problem was not a shortage of ATP. Rather, it was the mess created by all the workarounds my body was doing to maintain a level of ATP that could keep me alive. So, I started taking the following pre-bed stack. It is meant to be a clean-up the mess, anti-inflammatory: - 2g Vitamin C - 500 mg reduced glutathione - 500 mg curcumin (I prefer BCM-95) - 1-5 mg melatonin (depending on activity level) - 100 mg CoQ10 (I am also considering adding Ashwagandha to the stack) As of today, I workout 4-5 times per week, with 2 sessions of boxing (like punching in the face, not the aerobic variation), 1 heavy lifting session (usually squats) and 1-2 metabolic circuit sessions. Sure I feel tired at times, but it is not liked the deep, extreme fatigue I felt before starting this stack. Hope this helps.
- delbel 8y ago
  I'm curious. if you occasionally have fatigue in a cycle, consistent with some kind of infection growth life cycle, you should try removing vitamin C and gluthatione for 10 days and see if you feel even better. if you do, you need to go see a doctor to get screened for parasitic infections that cannot be found with just looking at a regular blood test. 99% chance you don't have one, but I am curious.
  - fasteo 8y ago
    Interesting comment. I have thought about this in the past as mitochondria, roughly speaking, is a bacteria. As such, it is in a constant flux of fission and fusion cycles and targeting this cycle is a potential target to treat my disease. For a fascinating experiment, check out Longecity's "Manipulating mitochondrial dynamics" post [1]. Worth reading. Based on this, I am still trying to set up a protocol for my disease, but have not tried that yet. [1] https://www.longecity.org/forum/topic/94224-manipulating-mitochondrial-dynamics https://www.longecity.org/forum/topic/94224-manipulating-mit...
twodave 8y ago
There are about half a dozen solid rock band names in this headline: Hello [City], we are [Choose one below]! Duh nuh nuh nuh nuh, Duh nuh, Duh nuh nayayayayay - Inflammation Uncovered - Mitochondrial Connection - Elusive Mitchondria - Elusive Inflammation - Mitochondria Uncovered ...
baccheion 8y ago
Vitamin D3 (+ K; 10 IU D3 : 2 mcg+ MK-4) + chelated/TRAACS magnesium. Magnesium is released by the body to clear inflammation. Vitamin D induces autophagy, and counters inflammation and oxidation. Riboflavin (selenium, vitamin E, etc) is involved in the recycling of glutathione. MSM + silicon (monomethylsilanetriol) + vitamin C. 4g:1g MSM:C.

242 points by dtawfik1 8y ago

This is actually very interesting. Low-grade inflammation is often linked to aging and cancer developments, it is however often unclear whether its cause/effect or correlation - https://academic.oup.com/biomedgerontology/article/69/Suppl_1/S4/587037 https://academic.oup.com/biomedgerontology/article/69/Suppl_... But mechanisms of inflammation are many and still pretty illusive, this is a great step towards understanding aging mechanisms in general.

deleted 8y ago
[deleted]

jgalvez 8y ago

Ray Peat anyone? :)

asdfasdfdavid 8y ago
Absolutely, nobody knows better how to take care of our mitochondria than Ray Peat.

reasonattlm 8y ago

Oxidative stress and inflammation go hand in hand. Aging has rising levels of both. Mitochondrially targeted antioxidants such as SkQ1 were first approved for use against inflammatory eye conditions. They act to dampen the consequences / amount of inflammation, and do this by cutting down on oxidizing molecules produced within mitochondria. They were first developed out of an interest to slow aging through this sort of modulation of mitochondrial oxidative stress and damage. They do slow aging to some degree, but don't do anywhere near as well as calorie restriction - say 10% in flies, something less than that in mice, which isn't impressive. The first earnest human trials for mitochondrially targeted antioxidants such as MitoQ (which from the studies is actually less effective than SkQ1) suggest it can reduce the impact of oxidative stress or inflammation on the smooth muscle cells in blood vessel walls. Their dysfunction produces some fraction of the stiffening of blood vessels with age. That stiffening causes raised blood pressure, which in turn causes too many bad things to list here. So these are not massive effects. You can probably do as well as MitoQ by bumping up your exercise level to the next tier. But then you can always both exercise and take a mitochondrially targeted antioxidant. The costs are not high, so it may be worth it based on the preliminary data. Not a cure for aging, and thus not worth spilling immense amounts of ink and effort over it. Just something to think about doing and then get on with better development projects with better expected outcomes.

SubiculumCode 8y ago
Then melatonin supplementation might be the way to go.... https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+mitochondrial+stress&hl=en&as_sdt=0,5&as_vis=1 https://scholar.google.com/scholar?as_ylo=2018&q=melatonin+m...
fasteo 8y ago
Wow, I did not expect to find you here reason !! mitomutant from Longecity speaking.

0x8BADF00D 8y ago

I wonder why we developed the STING protein in the first place. Was it perhaps an early form of immunity, or a precursor to an immune response?

maxander 8y ago
The name stands for STimulator of INterferon Genes, where interferons are essentially message-carrying molecules involved with the immune system. STING protein, I believe, is essentially a detector which gets triggered when a cell is invaded by a virus or encounters a parasite. For that, it still serves an important purpose.

jonmc12 8y ago

If you are interested in more information about Autophagic processes, this video interview is great: https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patrick_brings_nerd_level_video_on/ https://www.reddit.com/r/fasting/comments/6qobj7/rhonda_patr... Rhonda Patrick interviews Dr Guido Kroemer, an expert in Autophagy. Its one of the most accessible, well-referenced and thorough discussions on Autophagy (including Mitophagy), that I've come across.

dpatrick86 8y ago
Transcript and other resources available here. https://www.foundmyfitness.com/episodes/guido-kroemer https://www.foundmyfitness.com/episodes/guido-kroemer Thanks for sharing!
- ra 8y ago
  Dr Rhonda Patrick's podcast, Found My Fitness, is excellent.

king_panic 8y ago

2012: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536340/

MarkThief 8y ago

So this could be what is causing all these nearly undiagnosable cases of autoimmune disease?

wolco 8y ago

This is highly interesting. After taking ciprofloxan 10 months ago I'm still trying to get my damaged mitochondria back in order.

phkahler 8y ago
If it affected your tendons Magnesium is recommended. I'd also speculatively suggest iodine (a few mg per day) and glycine (1-20 grams per day). I am not a doctor, but then that's who prescribed you that crap ;-)
- monotone666 8y ago
  I have chronic fatigue likely brought on by mitochondrial dysfunction. Iodine ended a 12 month long mono infection and is the difference between having enough energy to spend the day reading.
DoreenMichele 8y ago
I'm curious what you mean by that. It sounds like an odd way to frame it.
- wolco 8y ago
  I've personally never struggled so hard to recover from anything. I couldn't do it justice in a short post. Lost 75 pounds in a 45 days. Heartrate over a 100 for a month. Here is a link to another nature article on it: https://www.nature.com/articles/d41586-018-03267-5 https://www.nature.com/articles/d41586-018-03267-5
  - DoreenMichele 8y ago
    Yes, I've recovered from long term prescription drug use. It was awful. I just thought mitochondrial damage was a strange framing. Thanks. Edit: The article does talk about mitochondrial damage, though it didn't appear at first glance to address this. It's towards the end of the article.
8y ago

ArtWomb 8y ago

One mental model which may help in visualizing "oxidative stress" in mitochondrial networks is to liken it to a "first-order phase transition" in solid-state physics. Gene expression regulates structure. And structure determines function. But whereas a typical sample of inorganic material may possess a handful of stable states under room temperature conditions. Nuclear genomics in mammals express 1000s of proteins. MIT's Broad Institute has begun compiling a reference atlas: MitoCarta 2.0: An Inventory Of Mammalian Mitochodrial Genes https://www.broadinstitute.org/scientific-community/science/programs/metabolic-disease-program/publications/mitocarta/mitocarta-in-0 https://www.broadinstitute.org/scientific-community/science/...

narrator 8y ago
If you could acurately simulate biological systems with a computer model, you could do drug development in the cloud without the need for clinical trials. Unfortunately, protein folding and even predicting whether a molecule will be an agonist at a particular receptor site are very slow algorithms.
- JunkDNA 8y ago
  Accurately simulating biological systems in the cloud to run a virtual clinical trial is like trying to predict the exact weather for Washington DC at a specific date and time hundreds of years from now using weather forecast models. It’s pretty much impossible with current biomedical knowledge. To simulate humans well enough to eliminate a clinical trial, you would have to simulate every single cell, organ, and organ system as well as the substantial population of bacterial and fungal microorganisms that live on and inside humans (as well as all their unique biology too). Building such a simulation would require a level of knowledge of biology that the human race currently does not possess.
  - dflock 8y ago
    Also, computronium.
  - snaky 8y ago

fasteo 8y ago

Interesting post and comments, as usual. I wanted to give some pragmatic information related to this. I have a genetic condition that makes my mitochondria to malfunction. I was diagnosed about 10 years ago. At first, I started taking supplements to increase the production of ATP, but my "vitality" did not improve much. I could workout normally, but my recovery ability was poor, and from time to time I would just crash and burn for 2-3 days. After much reading, I came to the conclusion that the problem was not a shortage of ATP. Rather, it was the mess created by all the workarounds my body was doing to maintain a level of ATP that could keep me alive. So, I started taking the following pre-bed stack. It is meant to be a clean-up the mess, anti-inflammatory: - 2g Vitamin C - 500 mg reduced glutathione - 500 mg curcumin (I prefer BCM-95) - 1-5 mg melatonin (depending on activity level) - 100 mg CoQ10 (I am also considering adding Ashwagandha to the stack) As of today, I workout 4-5 times per week, with 2 sessions of boxing (like punching in the face, not the aerobic variation), 1 heavy lifting session (usually squats) and 1-2 metabolic circuit sessions. Sure I feel tired at times, but it is not liked the deep, extreme fatigue I felt before starting this stack. Hope this helps.

delbel 8y ago
I'm curious. if you occasionally have fatigue in a cycle, consistent with some kind of infection growth life cycle, you should try removing vitamin C and gluthatione for 10 days and see if you feel even better. if you do, you need to go see a doctor to get screened for parasitic infections that cannot be found with just looking at a regular blood test. 99% chance you don't have one, but I am curious.
- fasteo 8y ago
  Interesting comment. I have thought about this in the past as mitochondria, roughly speaking, is a bacteria. As such, it is in a constant flux of fission and fusion cycles and targeting this cycle is a potential target to treat my disease. For a fascinating experiment, check out Longecity's "Manipulating mitochondrial dynamics" post [1]. Worth reading. Based on this, I am still trying to set up a protocol for my disease, but have not tried that yet. [1] https://www.longecity.org/forum/topic/94224-manipulating-mitochondrial-dynamics https://www.longecity.org/forum/topic/94224-manipulating-mit...

twodave 8y ago

There are about half a dozen solid rock band names in this headline: Hello [City], we are [Choose one below]! Duh nuh nuh nuh nuh, Duh nuh, Duh nuh nayayayayay - Inflammation Uncovered - Mitochondrial Connection - Elusive Mitchondria - Elusive Inflammation - Mitochondria Uncovered ...

baccheion 8y ago

Vitamin D3 (+ K; 10 IU D3 : 2 mcg+ MK-4) + chelated/TRAACS magnesium. Magnesium is released by the body to clear inflammation. Vitamin D induces autophagy, and counters inflammation and oxidation. Riboflavin (selenium, vitamin E, etc) is involved in the recycling of glutathione. MSM + silicon (monomethylsilanetriol) + vitamin C. 4g:1g MSM:C.