Overhyping the Effects of Hyperbaric Oxygen Treatment on Aging

An interesting open access paper was recently published on the effects of hyperbaric oxygen treatment on telomere length and cellular senescence in immune cells taken from blood samples. 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, but this attitude doesn't extend to the rest of the publicity, unfortunately. When one runs a business based around offering hyperbaric oxygen treatment, one must make hay while the sun shines, and extract every last drop of marketing juice from every study funded. Hence there are media articles out there at the moment 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.

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. 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 celular 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.

Comments

A reminder that the media really are mostly a bunch of complete morons.

Posted by: Matt at November 20th, 2020 4:46 PM

Not morons at all! And not just the media; the press release was released by "American Friends of Tel Aviv University", and the University and the scientists involved (from my experince of PR) willhave had a hand in it too, All opportunists who see a chance for making a buck and care little for factual reality, or the damage that misinformation can do.

Posted by: William at November 22nd, 2020 2:21 AM

There's epidemeology showing positive relationships between living in higher altitude with longevity, which would be the opposite conditions of HBOT; lower oxygen and lower air pressure with elevation while HBOT is high oxygen high pressure. If HBOT gives any rejuvenating benefit then perhaps it would be hormesis from brief exposure but I doubt it

Posted by: Bridgeburn at November 22nd, 2020 2:30 AM

I was too harsh saying they are morons. It's more like they are underpaid and have little incentive to write actually informative articles about science. And well, let's face it. If they are journalists, they are not scientists.

So the sad state of affairs is that global warming is a problem for 100 years from now and life extension comes from high pressure oxygen treatment.

Posted by: Matt at November 22nd, 2020 3:06 AM

Honestly..there is nothing wrong with this

People like Aubrey DGrey, David Sinclair, this website, etc etc.....have been promoting "real longevity science" for years now....and the majority of the public couldn't care less

At least these types of articles keep the public eye on the target and excite them for a bit..before they go back to the Kardashians...

Posted by: James Burnbrae at November 22nd, 2020 5:16 AM

Great article thanks for the clarification.
1) From what I understood from an article I've read (haven't read the paper) the protocol used here was different than other hyperbaric pressure treatments in that the reduction in oxygen back to normal was done rapidly and this what was responsible for the said anti-aging effects?
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?

Posted by: Ferri at November 22nd, 2020 6:30 AM

Hi Ferri! Just a 2 cents. Sorry for the length of message.

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''

Posted by: CANanonymity at November 22nd, 2020 4:46 PM

Answer to @CANanonymity:

Interesting thoughts!
Regarding (2) I'm not sure it's the case where acute "solid offensive" is always better than a "longer battle". For example in the case of the Covid-19 virus where it's said that in many cases what causes death is actually the too acute response of the body rather than the virus. Another example is an autoimmune disease such as Alopecia Areata where even a one time acute "solid offensive" is not desired. It seems to me that it's both the quality and the quantity of the response that matters and that not always greater quantity is better than lesser quantity.

Posted by: Fermi at November 23rd, 2020 2:43 AM

Its all very unconvincing CANanonymity - hormesis is a fine line, especially as increased cell turnover via the stem cell reserve with longer replacement telomeres is exactly what we'd expect from the destruction of older/weaker cells via increased oxidative stress. But in this case the result would be a reduction in lifespan even though a naiive interpretation of biomarkers would suggest short term improvement.

Posted by: Mark at November 23rd, 2020 8:37 AM

Hyperbaric oxygen treatments are easy to sell with a minimal upfront investment, and probably should do well for a while in upscale suburban areas with some Facebook advertising. "What does it do" isn't as important as "can it sell?".

Think of tanning beds....

Posted by: nobody at November 23rd, 2020 10:28 AM

Hi came across this post via a Twitter link by someone sceptical of the claims and media hype. I myself do not have an academic scientific background but the way the claims were presented seemed illogical and lacking something that I could not put my finger on. A deeper look revealed that despite the impression some articles gave this was not general telomere boosting but very specific to the immune system.
I really appreciate the nuance in Reasons original post and the thoughtful replies.
I feel much more enlightened and can now understand the issues much better.
I am however left dismayed and a bit furious at how poorly journalists in the mainstream media report scientific stories. It really is semi dishonest and hugely misleading.
Just wanted to give positive feedback to show my appreciation for the intelligent informative analysis.
In my opinion over claim is very counterproductive to science in the long run and I wish there was less of it.
Nuance is a great ally.
Best wishes folks.

Ps please don't make my email address display publicly? Thanks

Posted by: Adorable Scouser at November 23rd, 2020 11:23 PM

Guess I'll put off my investment in a home HBOT tank...
:/

Posted by: bmack500 at November 24th, 2020 8:03 AM

A year ago I did quite a bit of reading on HBOT . One of the results that stood out was that it was reported to change naturally graying hair back to it's original, youthful color. That certainly sounds like some sort of regeneration is happening. I never read any explanation or even theories about why this happens and it is not even mentioned in this paper so maybe it is person or treatment variation sensitive. Given that one of the reasons hair turns gray is reported to be a natural accumulation of hydrogen peroxide in the hair cells then reversing this by adding oxygen makes no sense. But the body is an ultra-complicated system. Who knows?

Posted by: Dean at November 25th, 2020 10:20 AM

The reason hair goes gray followed by white is because the gene for the pigment has mutated or become damaged in some followed by all of the follicles.
Every new cell copied in the future would contain the defect.
A reliable study showing that HBOT reverses gray hair would be interesting but even if HBOT lengthens telomeres I don't see how graying hair is reversible.

Posted by: Dave at November 28th, 2020 9:40 AM

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