Good podcast on hypoxia and more
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@John_Hemming, thanks for the podcast! Very interesting. I have some further questions if you dont mind:
- overexpression of NRF2 seems to be good for health. Does this means the bad guy is NF Kappa b?
- Dont we have any metric to guide us using hyperoxia exercises? Right now it’s all hoping the intervention is working?
- The “growth factor” part in VEGF makes me not want to activate it as this means aging, at least when its related to IGF, GH, mTor. Are those different paths vs Vegf?
NF Kappa B is generally a sign of over inflammation, but during differentiation I think the situation may be different.
The problem with hypoxia is that we don’t really know what is best in terms of direct exposure to changes in partial pressure of oxygen. There is a lot of research in subsets such as the hypoxia caused by exercise.
I don’t have a good answer on VEGF.
surprised no one has mentioned this system
EWOT with hypoxic training
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Fascinating stuff this. Criminally understudied for healthspan and lifespan in humans outside of elite sports.
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@murraci I agree. But based on a few tidbits I have become convinced that I can augment the benefits of exercise by artificially stretching my adaptive homeostasis capabilities, focusing on extremes in:
(1) hi/low co2/o2 (shallow breathing to hold SpO2 at 90%, exhale breath holds, nasal breathing during exercise, wim hoff breathing)
(2) hot/cold (sauna vs cold exposure)
(3) fat/carb metabolism (fasting, fasted exercise for fat burning)
(4) hi/lo sensory environment (sensory deprivation at night: light, stress, food, etc. plus extra stimulus during day: sunlight, morning exercise)
(5) of course HIIT exercise and low intensity endurance and strength and range of motion and balance, etc
Thoughts?
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That’s a great list. I would agree with most of your thoughts here. I strongly believe the secret to longevity is constantly midly stressing your body to get it to adapt and become stronger. There are many ways to stress it.
So yeah stuff like exposing the body to low and high oxygen environments, cold and heat, hunger (or cheat with rapa) and feasting, exercise (endurance, HIIT, stretching and resistance) and rest, etc. Also agree best to exercise in the morning if you can. It’s all about constantly giving your body a different look so-to-speak.
I wouldn’t reduce hypoxia to simply enhancing the benefits of exercise though. It of course does but it also produces desirable adaptations on its own even without exercise. I’m splashing out on converting our bedroom to a hypoxic chamber as I’ve become convinced it’s a really powerful intervention. We plan to sleep at altitude moving forward. It’s very expensive so not everyone will do it but it’s the only real way one can get exposure for a sufficient hours a day to really see the full spectrum of benefits one can get from hypoxia.
Of course the shallow breathing does really work too as Millet stated in that clip. I can also see myself adding that to my program.
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I’m more and more interested in intermittent hypoxia therapy.
This paper by Matt Kaeberlein showed that it doubles lifespan in worms: Intermittent hypoxia therapy engages multiple longevity pathways to double lifespan in C.elegans 2022
The protective effects ischemic preconditioning (IPC) in mammalian systems requires the activity of G-protein coupled receptors, and inhibition of Gi/o with pertussis toxin can abrogate this protection(31). While IPC has been studied for decades, and the use of various IHT regimes to improve athletic performance equally well established(32), the clinical use of hypoxia in western medicine has been relatively limited(33). However, recent work shows that exposure to continuous hypoxia can rescue mitochondrial dysfunction in a mouse model of the mitochondrial disease Leigh syndrome, while an IHT regime failed to show a similar results(34, 35). Mitochondria are the primary consumers of molecular oxygen in the cell and mitochondrial dysfunction is one of the key hallmarks of aging(36). The role of oxygen in the aging process, primarily as a putative source of damaging ROS has been hypothesized for decades, however low oxygen therapies have shown limited results in increasing longevity(37). Our results suggest that organismal responses to low oxygen are complex, and that sensory or reproductive signals triggered by acute hypoxia exposure, rather than decreased total lifetime oxygen levels, can trigger endogenous protective pathways to dramatically increase lifespan in wildtype animals. Further studies are warranted to determine whether the effects of IHT on longevity are conserved in mammals with the potential to promote healthspan and lifespan in humans.
Hypoxia is currently being studied in an RCT for Parkinson’s disease: Parkinson’s disease – #371 by adssx
There’s the protocol: Randomized controlled trial of intermittent hypoxia in Parkinson’s disease: study rationale and protocol 2024
They showed safety in a phase 1 trial. The researcher told me: “Our the main manuscript from our first study is currently in revision, and we are writing up the manuscript for the second study as all lab results have just come in.”
If successful, it might explain some mysteries of Parkinson’s disease: why are exercise, smoking, and altitude protective?
I’ll give a try to intermittent hypoxia, trying to reproduce the protocol in the PD study:
45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks
A commercially available hypoxic generator (b-Cat ALT-120, B-cat High Altitude, Tiel, the Netherlands) is used, which is similar to devices regularly used in hypoxic training studies
the device automatically titrates the correct fraction of inspired oxygen (FIO2) of 0.16 in a closed feedback loop with an FIO2 sensor
I also found this machine but can’t find its price: https://www.cell-oxy.com/
I did this summary of variations in partial pressure of Oxygen in 2022
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I’m surprised, there are many ongoing trials of intermittent hypoxia therapy: ClinicalTrials.gov
For instance:
And a dozen trials of IHT for spinal cord injuries?!
One trial in Israel is comparing Intermittent Hypoxic Training (IHT) Versus Hyperbaric Oxygen Therapy (HBOT) for Aerobic Performance.