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Not ignore, but 5 days of intense excitement till I understood the disclaim below. The writer is saint Dr. Aubrey de Grey, for rejuvenation bioengineer as me, a computer scientist engineer in a medical doctor incremented MD doctorate.
Overhyping the Effects of Hyperbaric Oxygen Treatment on Aging
Condensed simplified summary by me, useful if lost in reading above. My comments are so.
1. An interesting open access paper was recently published. I use the word "interesting" quite deliberately, because that is exactly and all that this research is. The paper is appropriately formal and modest on that front, publicity breathlessly telling us that hyperbaric oxygen treatment reverses aging. This is ridiculous, and only makes it harder for the better end of the industry to make progress.
It is best summarized as hyperoxic hypoaxic paradox milked for telomere extension in circulating immune system in peripheral blood. It is not the singularity but a clear medical advance useful for some medical conditions.
Per the paper, hyperbaric oxygen treatment causes average telomere length to grow by ~20% and markers of cellular senescence to decrease by ~35% in populations of circulating immune cells.
Immune system strengthening will indirectly benefit the patients. But a published paper has found no improvements in fighting Covid-19!
This doesn't tell us that hyperbaric oxygen treatment is an amazing rejuvenation therapy, any more than the NAD+ and mitochondrial function data for exercise tells us that exercise is an amazing rejuvenation therapy. In both cases we already know the bounds of the possible. We know that these interventions don't turn older people into notably younger people. If we're calling exercise and hyperbaric oxygen treatment rejuvenation therapies, then the term "rejuvenation therapy" is meaningless.
What this does reinforce is the point that peripheral blood immune cell parameters can be very disconnected from the overall state of aging. We know that telomere length as assessed in these cells is a truly terrible measure of aging. Circulating immune cells are prone to large variations in the pace of cellular replication in response to circumstances. Immune cells replicate aggressively when provoked by the presence of pathogens or other issues requiring a coordinated immune response. Telomere length shortens with every cell division in somatic cells: in immune cells, telomere length thus has a very wide spread across individuals, varies day to day, is just as influenced by infection status and other environmental factors as it is by aging. It is just not all that helpful as a measure of aging, and downward trends with age are only seen in the statistics for large study populations.
It seems plausible that the same is true of cellular senescence in immune cells. Cells become senescent when they hit the Hayflick limit on cellular replication. Throughout much of life, the senescence of immune cells is likely more determined by replication pace (and thus immune challenges, the burden of infection) than by aging. And that is before we even get to the point that the authors of this paper used a less than standard measure of senescence, one for which it is possible to argue that it may or may not actually be representative of the burden of senescent cells in immune populations. Overall this data is all interesting, but I suspect that it tells us more about the poor relevance of the metrics chosen to anything other than the deeper aspects of immune function.
If hyperbaric oxygen treatment removed ~35% of senescent cells throughout the body, it would already be well known as a reliable therapy for arthritis, a way to reverse chronic kidney disease, a way to suppress inflammatory conditions, and an effective treatment for numerous chronic diseases of aging.
In mice, removing a third of senescent cells via senolytic drugs produces reliably large and beneficial outcomes, while hyperbaric oxygen treatment does not. So clearly it is not globally clearing senescent cells - and nor should any responsible party be trying to present reductions in senescent immune cells as indicative of global senolytic effects throughout the body. What is observed here is an effect limited to the way in which the immune system is functioning. There is some evidence for hyperbaric oxygen treatment to improve resistance to infectious disease such as influenza, and that is interesting in and of itself, but I feel that much of what is going on here is an attempt by certain parties to jump onto the longevity industry bandwagon, rather than responsibly focusing on a realistic view of what can be achieved with their chosen intervention.
Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells : a prospective trial
Hyperbaric oxygen therapy (HBOT) utilizes 100% oxygen in an environmental pressure higher than one absolute atmospheres (ATA) to enhance the amount of oxygen dissolved in body's tissues. Repeated intermittent hyperoxic exposures, using certain HBOT protocols, can induce physiological effects which normally occur during hypoxia in a hyperoxic environment, the so called hyperoxic-hypoxic paradox. In addition, it was recently demonstrated that HBOT can induce cognitive enhancements in healthy aging adults via mechanisms involving regional changes in cerebral blood flow. On the cellular level, it was demonstrated that HBOT can induce the expression of hypoxia induced factor (HIF), vascular endothelial growth factor (VEGF), and sirtuin (SIRT), stem cell proliferation, mitochondrial biogenesis, angiogenesis, and neurogenesis. However, no study to date has examined HBOT's effects on telomere length and senescent cell accumulation.
Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th session, and 1-2 weeks following the last HBOT session. Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed. Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20% following HBOT. The most significant change was noticed in B cells. There was a significant decrease in the number of senescent T helpers by -37.30% post-HBOT. T-cytotoxic senescent cell percentages decreased significantly by -10.96% post-HBOT.
In conclusion, the study indicates that HBOT may induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging populations.
Agree whole-heartedly with “A reminder that the media really are mostly a bunch of complete morons.”
2. The Hyperoxic-Hypoxic Paradox
Here is why I believe Hyperoxic-Hypoxic Paradox HHP is intermediate to Dr. Grey (HYPE) and publicity (Singularity). It means that it is worth trying on self but no recommendation (solely benefit immune),
Hypoxia is reduced oxygen. It slows down immune system and slows metabolism. When it battles invaders, clearly you want it to be very active. But not for long – increases age damage! You want it very active in small intervals. In fact, with modern environments in developed world, need is small. That is why longer age happens in developed world. But it reduces the immune system and the damage from Covid-19 is more than India. In fact, the damage from Covid-19 varies with prosperity of the state. Only morons find politicians to blame, for or against. Only working tool is lock-down, economic bother for less developed country as India could not sustain tull but intelligent lockdowns in second wave.
99% long lived are found in mountainous regions. Common to them is low metabolism. All of this is paradoxical, safety demands active immune system! But that causes fast aging! As was seen in HBOT, telomeres grew only in hypoxia. But hypoxia kills! How can you get fake hypoxia? By subjecting patient to high pressure oxygen first, periodically reduced to normal air. That is what HHP is.
If true, there exists a class of people doing so! These are divers who are subjected to hyper pressures on descent and have to surface with stops on way up to fight bends. They do have elongated telomeres but in blood only. HHP is no good for aging undo but good for immune system. Precisely what I need as fighting no-cure in mm diseases. So my intermediate position.
Death is a process, legally after heart stops. That is followed by half hour during which brain dies. Cryonists freeze it then. Totally different are Cryobiologists who study effects of cold on animals and plants. Can death be followed by reversible cryopreservation? Not only good for this, but also hibernation. Will happen by 2050. Only 30 more years! Want to live till then as I will be under 100 then.
HHP is doable by HBOT protocol today. That is probably not the only way. Divers can be simulated by a open well with timed moving machine in 200 m of water. Its trajectory and stop periods can be programmed and fully in control of the bioengineer! No need for any patient to know.
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3. I think we have to tamper our joy and hope of this therapy, not to say it is not useful, but some studies did not find such results; albeit, as you said, it may be due to the procedures differing.
''The HBOT protocol was administrated in a Multiplace
Starmed-2700 chamber (HAUX, Germany). The
protocol comprised of 60 daily sessions, five sessions
per week within a three-month period. Each session
included breathing 100% oxygen by mask at 2ATA for
90 minutes with 5-minute air breaks every 20 minutes.
Compression/decompression rates were 1 meter/minute.
During the trial, neither lifestyle and diet changes, nor
medications adjustments were allowed''
''Whole blood samples were collected into EDTA tubes
using a standard technique, at baseline, at the half-point
of the HBOT protocol (30th session), the day of the last
HBOT session (60th session) and 1-2 weeks following
the last HBOT session''
This specific treatment could explain why they saw telomere elongation...
''Exposing cell cultures to a hyperbaric environment has
been previously suggested to induce significant
oxidative stress and premature cells senescence [30].
However, this was based on isolated cells grown in a
hyperbaric incubator and not on the complex biological
system of humans as in this study. Similar to the current
study, a previous prospective one-year observational
study in divers exposed to intense hyperbaric oxygen,
showed significant telomere elongation in leukocytes ''
Thus, what is happening here, is not so much a use of extra O2 (100% O2) for ATP creation (mitoOXPHOS/oxidative phosphorylation)...but rather this causes a hypoxia in the body, and this was demonstrated in cell cultures (fibroblast) that low O2 makes much more numerous replicative bouts/population doublings. Thus, post-pones cell Leonard Hayflick's limit. So long as there is enough ATP in the cell to 'function enough'; this was shown with hormesis inducing a reduction of ATP in the cell but in doing so it caused reduction of the mitochondrial membrane potential and ROS emissions at the Complex I in ETC (electron transport chain) of mitochondrial inner membrane (if the membrane potential is lowered (a bit), the ROS is lowered too; so long as it is kept, if the potential is going too low then ROS elevates once again; it's a type of 'bell-curve' 'U-curve' shape graphic with ROS rising or lowering depending on state of potential), this is what is called 'mitochondrial depolarization'..when the mitomembrane potential becomes depolarized (which can cause cataclysmic reduction of ATP production/cell apoptosis) and then ROS will increase; when polarized, ROS is kept minimal or near-nill and there is then sufficient ATP production (at the electron-proton gradient that go through the proton pump).
Thus, what I think is really happening is a 'pseudo hypoxia' happens when you are exposed to many sessions (30-60 sessions) of repeated 100% O2 exposure; the body basically slows the metabolism due to this, and does a bit like, as they said, divers that go underwater and have pseudo hypoxia; same as people living in high altitude (mountains top), they face reduction of O2 and their blood/lungs/heart adjusted for such low O2 environment; under water there is low O2; in a hyper baric chamber..it ends up the same result..it causes pseudo hypoxia and reduces the O2 intracellularly, this will cause a sort of hormesis and activate HIF-1a (Hypoxia Inducible Factor 1-alpha) a master regulator of the hypoxia response in the body; crucial to survive ischemia and hypoxia (I live this (due to atherosclerosis), I have had ischemia events many times (lack of O2 to organs)...same as hypoxia), HIF-1 is what protects against ischemia events and makes sure the cell never falls too low otherwise ATP will catastrophically lower -> cell apoptosis/necrosis/senescence. Ischemia and hypoxia can cause necrosis, gangrene, cyanosis (cyanide causing anoxia), and destruction of tissues if there is not enough O2...I say 'not enough O2'...but it's not really O2...what it is Is ATP (Adenosine TriPhosphate); if ATP is too low then yes...you will see these cellular events happen (such as apoptosis or necrosis; or it cell may survive and enter senescent state instead).
Animals that live longest, bowhead whales, groenland sharks, iceland clams and giant seaturtles, live 175 to 500 years...all of them live 'in hypoxia'..under water, just like divers diving deep beneath (water is low O2 environment), it is almost ironic that 99% of all the 'long-lived' animals are all Underwater/'Aquatic' animals....it's not a coincidence. And 100% of them have 'ultra-slow metabolism'.
Now, certain animals Also live under water and don,t live long - Zebra fish...the shortest living aquatic animal; Gold fish...etc...it's not because underwater that necessarily live longer; they live in low O2 and still live short life. But that is where the other animals use the mechanism to their advantage (unlike these short living fish), cells cultured under lower O2 replicate Longer and post-pone Hayflick limit...
Now why? Because ROS is reduced in that case, if ROS is reduced (because there is less O2 to begin with; let's remember that ROS is OF O2 (R.O.S./Reactive Oxygen Species -> need Oxygen first); so with Less Oxygen; Less ROS being made...cause..less O2 available. Now, DNA damage can still happen despite a reduction of ROS; it's what happens when intracellular ATP levels fall so low. They can't be Too low, 'low-enough' is viable, not Too low/Nill/Null/0/Absent. No ATP = cell death. When hypoxia happens (by lowering internal O2 levels), cells can proliferate and replicate faster and in that moment they can repair better, and even elongate telomeres; thus, this pseudo hypoxia (by excess O2 exposition in hyperbaric chamber) would reduce ROS in cells, reduce senescence burden (or, at least, reduce senescent cells from accumulating; thus, 'freeze' the senescent markers or lower them), and this would end up just like hypoxia, diving, exercise or Calorie Restriction; a form of rejuvenation would happen and there would be Visible youthening of the body.
2) "Throughout much of life, the senescence of immune cells is likely more determined by replication pace (and thus immune challenges, the burden of infection)" does this mean that an individual's immune system cells which are more active due to allergies, herpes, tattoo (the immune system attacks the tattoo ink) will senesce faster and shorten the individual's life?
Technically, yes, but it's more nuanced; an overactive immune system is not good (in the long run if it is chronic/never stops/never settles down); you need an 'on-demand' immune system that can 'mount' a 'solid offensive' -only and when- it is needed; after that is Must stop activity and be quiescent. So it's the 'hit and run' tactic with the immune system; it must do this quick and get it over with..and then leave right away. The better it can do that the better it deals with pathogens, cancer, virus, bacteria and so forth; it must not be a 'long drawn out' battle of the immune system against the invaders...the longer it 'lingers' the more potential for the immune system to fail or stay 'hyperactive''overdrive-mode'...and then this can cause 'auto-immune' diseases (lupus for example) and even atherosclerosis (my diesease, is also an 'overactive immune system' disease), when T-cells (T-helper/T-cytotoxic), NK-cells, Macrophages and other immunecells of the immune systhem that order killing of invaders..
If you have a solide immune system, it is better and you Need Immunity to live to a 100+ years old no way around that; but, your immune system must 'be dosed' and dose itself; and has to subside once a pathogen is phaged, animals that live the longest have solid immunity but it is also 'latent' and 'quiescent'...only when needed does it 'active/fire up' (and yes that happens often...your immune system must still slow down too, at least sometimes).
Just a 2 cents.
PS:''Repeated
intermittent hyperoxic exposures, using certain HBOT
protocols, can induce physiological effects which
normally occur during *hypoxia in a hyperoxic
environment*, the so called **hyperoxic-hypoxic paradox**''
''On the cellular level, it was
demonstrated that HBOT can induce the expression of
**hypoxia induced factor (HIF)***, vascular endothelial
growth factor (VEGF) and sirtuin (SIRT), stem cell
proliferation, mitochondrial biogenesis, angiogenesis
and neurogenesis''
3. I think we have to tamper our joy and hope of this therapy, not to say it is not useful, but some studies did not find such results; albeit, as you said, it may be due to the procedures differing.
''The HBOT protocol was administrated in a Multiplace
Starmed-2700 chamber (HAUX, Germany). The
protocol comprised of 60 daily sessions, five sessions
per week within a three-month period. Each session
included breathing 100% oxygen by mask at 2ATA for
90 minutes with 5-minute air breaks every 20 minutes.
Compression/decompression rates were 1 meter/minute.
During the trial, neither lifestyle and diet changes, nor
medications adjustments were allowed''
''Whole blood samples were collected into EDTA tubes
using a standard technique, at baseline, at the half-point
of the HBOT protocol (30th session), the day of the last
HBOT session (60th session) and 1-2 weeks following
the last HBOT session''
This specific treatment could explain why they saw telomere elongation...
''Exposing cell cultures to a hyperbaric environment has
been previously suggested to induce significant
oxidative stress and premature cells senescence [30].
However, this was based on isolated cells grown in a
hyperbaric incubator and not on the complex biological
system of humans as in this study. Similar to the current
study, a previous prospective one-year observational
study in divers exposed to intense hyperbaric oxygen,
showed significant telomere elongation in leukocytes ''
Thus, what is happening here, is not so much a use of extra O2 (100% O2) for ATP creation (mitoOXPHOS/oxidative phosphorylation)...but rather this causes a hypoxia in the body, and this was demonstrated in cell cultures (fibroblast) that low O2 makes much more numerous replicative bouts/population doublings. Thus, post-pones cell Leonard Hayflick's limit. So long as there is enough ATP in the cell to 'function enough'; this was shown with hormesis inducing a reduction of ATP in the cell but in doing so it caused reduction of the mitochondrial membrane potential and ROS emissions at the Complex I in ETC (electron transport chain) of mitochondrial inner membrane (if the membrane potential is lowered (a bit), the ROS is lowered too; so long as it is kept, if the potential is going too low then ROS elevates once again; it's a type of 'bell-curve' 'U-curve' shape graphic with ROS rising or lowering depending on state of potential), this is what is called 'mitochondrial depolarization'..when the mitomembrane potential becomes depolarized (which can cause cataclysmic reduction of ATP production/cell apoptosis) and then ROS will increase; when polarized, ROS is kept minimal or near-nill and there is then sufficient ATP production (at the electron-proton gradient that go through the proton pump).
Thus, what I think is really happening is a 'pseudo hypoxia' happens when you are exposed to many sessions (30-60 sessions) of repeated 100% O2 exposure; the body basically slows the metabolism due to this, and does a bit like, as they said, divers that go underwater and have pseudo hypoxia; same as people living in high altitude (mountains top), they face reduction of O2 and their blood/lungs/heart adjusted for such low O2 environment; under water there is low O2; in a hyper baric chamber..it ends up the same result..it causes pseudo hypoxia and reduces the O2 intracellularly, this will cause a sort of hormesis and activate HIF-1a (Hypoxia Inducible Factor 1-alpha) a master regulator of the hypoxia response in the body; crucial to survive ischemia and hypoxia (I live this (due to atherosclerosis), I have had ischemia events many times (lack of O2 to organs)...same as hypoxia), HIF-1 is what protects against ischemia events and makes sure the cell never falls too low otherwise ATP will catastrophically lower -> cell apoptosis/necrosis/senescence. Ischemia and hypoxia can cause necrosis, gangrene, cyanosis (cyanide causing anoxia), and destruction of tissues if there is not enough O2...I say 'not enough O2'...but it's not really O2...what it is Is ATP (Adenosine TriPhosphate); if ATP is too low then yes...you will see these cellular events happen (such as apoptosis or necrosis; or it cell may survive and enter senescent state instead).
Animals that live longest, bowhead whales, groenland sharks, iceland clams and giant seaturtles, live 175 to 500 years...all of them live 'in hypoxia'..under water, just like divers diving deep beneath (water is low O2 environment), it is almost ironic that 99% of all the 'long-lived' animals are all Underwater/'Aquatic' animals....it's not a coincidence. And 100% of them have 'ultra-slow metabolism'.
Now, certain animals Also live under water and don,t live long - Zebra fish...the shortest living aquatic animal; Gold fish...etc...it's not because underwater that necessarily live longer; they live in low O2 and still live short life. But that is where the other animals use the mechanism to their advantage (unlike these short living fish), cells cultured under lower O2 replicate Longer and post-pone Hayflick limit...
Now why? Because ROS is reduced in that case, if ROS is reduced (because there is less O2 to begin with; let's remember that ROS is OF O2 (R.O.S./Reactive Oxygen Species -> need Oxygen first); so with Less Oxygen; Less ROS being made...cause..less O2 available. Now, DNA damage can still happen despite a reduction of ROS; it's what happens when intracellular ATP levels fall so low. They can't be Too low, 'low-enough' is viable, not Too low/Nill/Null/0/Absent. No ATP = cell death. When hypoxia happens (by lowering internal O2 levels), cells can proliferate and replicate faster and in that moment they can repair better, and even elongate telomeres; thus, this pseudo hypoxia (by excess O2 exposition in hyperbaric chamber) would reduce ROS in cells, reduce senescence burden (or, at least, reduce senescent cells from accumulating; thus, 'freeze' the senescent markers or lower them), and this would end up just like hypoxia, diving, exercise or Calorie Restriction; a form of rejuvenation would happen and there would be Visible youthening of the body.
2) "Throughout much of life, the senescence of immune cells is likely more determined by replication pace (and thus immune challenges, the burden of infection)" does this mean that an individual's immune system cells which are more active due to allergies, herpes, tattoo (the immune system attacks the tattoo ink) will senesce faster and shorten the individual's life?
Technically, yes, but it's more nuanced; an overactive immune system is not good (in the long run if it is chronic/never stops/never settles down); you need an 'on-demand' immune system that can 'mount' a 'solid offensive' -only and when- it is needed; after that is Must stop activity and be quiescent. So it's the 'hit and run' tactic with the immune system; it must do this quick and get it over with..and then leave right away. The better it can do that the better it deals with pathogens, cancer, virus, bacteria and so forth; it must not be a 'long drawn out' battle of the immune system against the invaders...the longer it 'lingers' the more potential for the immune system to fail or stay 'hyperactive''overdrive-mode'...and then this can cause 'auto-immune' diseases (lupus for example) and even atherosclerosis (my diesease, is also an 'overactive immune system' disease), when T-cells (T-helper/T-cytotoxic), NK-cells, Macrophages and other immunecells of the immune systhem that order killing of invaders..
If you have a solide immune system, it is better and you Need Immunity to live to a 100+ years old no way around that; but, your immune system must 'be dosed' and dose itself; and has to subside once a pathogen is phaged, animals that live the longest have solid immunity but it is also 'latent' and 'quiescent'...only when needed does it 'active/fire up' (and yes that happens often...your immune system must still slow down too, at least sometimes).
Just a 2 cents.
PS:''Repeated
intermittent hyperoxic exposures, using certain HBOT
protocols, can induce physiological effects which
normally occur during *hypoxia in a hyperoxic
environment*, the so called **hyperoxic-hypoxic paradox**''
''On the cellular level, it was
demonstrated that HBOT can induce the expression of
**hypoxia induced factor (HIF)***, vascular endothelial
growth factor (VEGF) and sirtuin (SIRT), stem cell
proliferation, mitochondrial biogenesis, angiogenesis
and neurogenesis''