Hyperbaric oxygen therapy increases telomere length in isolated blood cells | Hacker News Reader

Hyperbaric oxygen therapy increases telomere length in isolated blood cells

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I am sorry if I am pessimistic but as a person with a genetics background, I am very skeptical when a measure has an error bar (or variance in this case) that includes no-change as a plausible explaination, i.e 25.68%±40.42

And, for my taste, 25.68%±40.42 is really bad style. 26%±40 is the amount of precision I would accept here.

Sorry for the rant, but I hate this obsession with chopping off digits people have.

25.68% ± 40.42 is not the same as 26% ± 40. If I am later trying to make a model to get the best estimate of <stat> by looking at a bunch of other people's measurements I will get a more accurate answer if more digits are contained.

When someone presents a state like 26% without the ± it's at least excusable, since it's avoiding making people think that 25.68% was short hand for 26.68% ± (0.005 ± 0.005)%, but when we're including the ± there is no good reason to chop off digits.

I do like the comment someone else has about reporting this as a range instead of with a ± sign, i.e. "-14.74 to 66.1 percent".

This is a pet peeve of mine as well; significant figures can be handy, but fundamentally they originated as a quick and dirty method of keeping track of uncertainty that was quite handy when doing calculations by hand, but is more or less obsolete today any time you have an actual quantitative uncertainty bound.

Sure, it's still convenient when writing things out in text to not continue adding digits far beyond the uncertainty of your value, but even so there is nothing "conservative" or in any way accurate about chopping off a bunch of digits (however imprecise) and replacing them with zeros. This is especially clear if we consider that we generally only ever consider sig figs in base 10, but in any computational context that number is definitely not stored in base 10.

If you really need the precision, you should use the raw data. Why is 25.68 precise enough and not 25.682393. Especially, since it is given in the abstract, and not in some kind of in detail supplement.

> If I am later trying to make a model to get the best estimate of <stat> by looking at a bunch of other people's measurements I will get a more accurate answer if more digits are contained.

But that is exactly what I doubt: that level of accuracy is not there. You predict a number that has been observed for a sample size of 35. If you now add sample #36, you will almost certainly get a different number. The (round-about, I did not calculate it in any way) two floating point digits are not accurate, they are chance. And a model predicting 25.72 would be no better than one predicting 25.94.

I think the intuition here is that if your error bars on the measurement are +- 40%, how can your accuracy on the error bars themselves be 4 significant figures, i.e. +-0.1%?

>how can your accuracy on the error bars themselves be 4 significant figures

They aren't, but that's still the number you got. Chopping off the digits means you're slightly changing the result. It's like Tic Tac and their "0g of sugar" label, despite being 90% sugar.

But the "0g of sugar" in TicTac is something totally different. The difference between 25.68 and 26 is 2% of the total number (while the error of 40 is almost 160%). The difference between 0.01 and 0 is 100%.

My point is that it allows these kinds of things to happen. What's the point in making the number less accurate? In probability the difference between 0.999 vs 1.0 is enormous and these kinds of things can happen when you just floor numbers.

I think the point is that given the size of the error bars, that much precision is not an accurate representation of the confidence we should have in the result. 25.68% might be the observed change, but it's not one we should have much confidence of being accurate, not to four significant figures. Glibly put, it's false precision.

No-one I've seen arguing for fewer significant digits says that a probability of 0.999 should be rounded to 1. Nor do they say it's ok to round 0.5 to 0.

There's no false precision. There's a whopping +/- 40% error bar! What can be said is that 26% is at least less precise on average. You've added a completely arbitrary 0.32 because of some obsession with decimals.

I think we're in agreement that the 0.32 is false precision?

No, because there's an error bar. Why is 0.32 the false precision and not some other random number.

I think if you're doing this level of nit-picking, it's far more likely that somewhere along the line a scientist used a 32 bit floating point in their analysis and blew the precision out of the water before the number even got to you.

Did you just divide by zero?

He divided by 0.1, otherwise he would never have gotten to 100%.

It’s probably not the number they got though; the STDDEV calculation or whatever error measure you choose will usually give you lots more decimal places. The decision was taken to round to 4 significant figures.

If you got 10 decimal places in your calculation, it would obviously be nonsense to give all of them.

Apart from number of digits (obvious big difference here if it was 40.41 vs 40.42?) I think that the numbers hide the fact that it's more like "I'd bet 5 bucks it's somehow positive" than a definite result you can pin your hat on.

On the other hand, I think this study should be the poster child of "please don't use p-values" movement. Everything significant, but floats around zero.

Generally the longetivity space is full of scams, especially the ones that sell something that doesn't need FDA approval (the last similar thing was a cream company marketed by Peter Diamondis a month ago)

A more informative way for them to express that range would be -15% to 65% where any negative % is no effect.

Where any negative number is a detrimental effect, here. :P

I saw this the other day, and something I don't understand about it is that ~40 years ago (so its dimly remembered) I did SCUBA training and oxygen toxicity is definitely a thing. So how is it that having a partial pressure of oxygen over a certain level while diving is toxic (delirium causing, which is especially dangerous underwater) but in a hyperbaric chamber is theraputic?

So telomeres shortening has a useful purpose in preventing runaway cell division right? So wouldn't artificially increasing their lengths increase cancer incidence, unless combined with other interventions for fighting cancer?

Telomere length in these studies gets used as a proxy for "cells acting young" or "cells acting old." Telomere length tends to shorten as you age and it gets looked at as a proxy for de-aging your body at the cellular level.

My mental model is this: Old cells have DNA mutations. Short telomeres tell the cells that they are old and should take it slow and be careful not to accumulate more mutations (senescence).

Any simple treatment like oxygen therapy, will be unable to fix DNA damage. It has mutated already and thats that. What it might do is to "lie" to the cell. "You are perfectly healthy", when it actually isn't. This has benefits, such as more rapid healing of injuries, and it has drawbacks such as cancer.

I think it's much more likely that old cells just have an accumulation of crud, like a house that is old and doesn't get cleaned enough.

We don't really have a good definition of "aging" because we don't really know what causes the body to give out after a certain amount of time has passed.

If a "cruddy" cell divides, then the two new cells will each have less then the original one.

Yes exactly. The article is hype.

The factual, reality answer is clearing senescent cells.

wouldn't hayflick limit still be a problem?

I don't know whether artificially increasing the length of telomeres increases the incidence of cancer, but cancer usually upregulates the creation of telomerase. Telomerase is part of an enzyme complex that lengthens telomeres.[0] In other words, most (almost all?) cancers end up lengthening their telomeres themselves.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915101/

The background section seemed to give an overview of this, however, I don't know how good this information is.

Bret Weinstein has much to say about that. I have been meaning to revisit his conclusions. Sorry I don’t have a more specific answer but I do remember very interesting things brought up by him.

Indeed — Weinstein’s claim (that I don’t have the expertise to validate) is that an enormous amount of biomedical research is performed on a subset of mice from a single breeding facility in Maine. These mice have abnormally long telomeres as compared to wild mice. This means they can take remarkable amounts of cellular damage before apoptosis (cell death) is triggered. The downside is that, by forestalling even desirable apoptosis, these mouse cells frequently end up cancerous.

If true, Weinstein says, this means that any compounds tested on these mice will necessarily look less damaging than they should, at least in the short run, because these mice have extensive regenerative capabilities. This might explain how certain drugs that cause heart damage (e.g. Vioxx) got approved — they looked safe in these super-mice, and human safety testing was too brief to catch the damage being done.

I’m only vaguely familiar with Weinstein’s claims, but you might find the following news article about some research I remembered going to a talk to about 5 years ago [0]. There’s a lot of proposals in the stem cell community like this, though I lack the insight to vet whether that’s happening in practice.

> About 80 percent of experimental drugs fail in human clinical trials because they are unsafe or ineffective, with some 30 percent found to be toxic in people despite promising results in animal studies

Effectively, a huge percent of drugs are failing out in clinical trials — so a few false negatives where the phenotypes aren’t measured correctly or are on an incompatible time scale seems pretty expected.

I haven’t seen anyone showing that “fixing” lab mice would’ve resulted in different animal trial results — is Bret claiming this?

[0] https://madison.com/wsj/news/local/health_med_fit/tissue-chi...

> I haven’t seen anyone showing that “fixing” lab mice would’ve resulted in different animal trial results — is Bret claiming this?

No one may have shown it, but it seems extremely unlikely to me that we are testing things in animals in the absolute optimum fashion to minimize failure in later human trials. It would be quite extraordinary if we happened to so luckily arrive at the ideal model organisms and procedures.

Presumably all the protocols we could use are not equally good, and good criticism of existing protocols towards improving their utility is important.

This may be a conservative view point, but showing that it would increase the translatability of mice trials to humans seems like a prerequisite for the criticism to change anything, though. No one is saying that our current animal trials are optimal, one of the professors in the news article I linked is quoted as saying the exact opposite "The animal models used to understand the safety and efficacy of drugs are flawed". It just is the case that retraining, to draw analogy to computational models, our model animal is not free because the evaluation of its performance after that change is much more complex and expensive than an ROC curve produced from labeled data.

Sheesh.

Well, sure. But even beginning to prove anything like this would be an extraordinarily expensive trial itself: what are you going to do, repeat trials for 100 substances in mice to see if you get a better alignment with later human results across potential substances than you do with current practices?

So instead, we talk about it, consider imperfect arguments, and do experiments that are somewhat silly until we start to become convinced that we've likely spotted some of the causal factors. That's what convinces us to eventually do the work that will show it.

> wouldn't artificially increasing their lengths increase cancer incidence

Yes, this is well-established in other species.

This seems to be an uncontrolled study. Stress reduces telomere length, and meditation has been shown to increase it:

https://www.tandfonline.com/doi/abs/10.1080/08870446.2019.17...

So it's certainly plausible that the placebo effect of being involved in a study to prevent aging could in itself have an effect on telomere length, even without the hyperbaric oxygen.

FWIW, as someone who had HBO therapy for five days a week for six months, I would not call it stress reducing.

Can I ask what requires HBO therapy for five days a week for six months?

I had a bone infection as a child that took several years to positively diagnose (it ended up being osteomyelitis). In an attempt to help my body fight off the infection, I was prescribed a couple hours a day in a HBO chamber.

HBO can be prescribed for infections of various kinds that are otherwise hard for the body to eliminate without assistance or straight antibiotics. This study aside, breathing pure oxygen for extended periods does wonders for the body's ability to repair itself.

The upside of that time was that bruises and mosquito bites healed practically instantaneously.

Thank you.

Diving accidents

Placebo usually shows up in subjective measures, or where the brain can intercede to effect the outcome. There should be a control group, but I would not expect telomere length to be effected by placebo.

I agree, but a control group is important to avoid problems with other unknown unknown variables that are included in the non fancy part of the placebo effect.

For example:

Did the subjects change their diet? If you are enrolled in a medical study, perhaps you may decide not to eat junk food everyday because the doctors will screen you next week. (My grandma used to "cheat" at her medical exams, and eat only healthy food a few days before, so the cholesterol was low. In some cases, it may not be a conscious decision.)

Does the length change with the season? This should be a known effect, but to avoid problems just get a control group.

Is it possible that the technicians made an error counting the length of the telomeres? It is probably an automated test, so I guess no.

Is it possible that the technicians cherry pick the more healthy white cells in the second part of the study and that skew the results? I guess picking the cells to analyze is not automatic. Perhaps they changed the team. Perhaps the initial screen test if boring and they just pick the fist cells they see, and in the other test they are more motivated and try to pick a good one. (Some patients were excluded because they have too few white cells in the second test, it is weird.) A good way to avoid this problem is to have double blind studies, so the technicians can not involuntary skew the results.

Hyperbaric oxygen isn't new, so I am putting this in the grey basket until I see it replicated. 25% telomere length increase and a senloytic effect just from breathing more O2 seems... weird. Not impossible, but weird that we would not have noticed such a thing yet.

On the topic of telomeres, Rejuvenation Tech is a YC company (S18) working on extending telomere length for health benefits.

Is there any evidence that people who regularly meditate live longer? Healthier people have longer telomeres but does a lengthening of the telomeres after they've presumably got shorter, then necessarily extend longevity?

Meditation? I cannot tell you.

As for medication, yes. The principle is that capture before is best, but extension after shortening conveys a therapeutic effect.

According to Scientific American guest blogger, JALEES REHMAN, lengthening you telomeres also lengthens cancer DNA telomeres:

https://blogs.scientificamerican.com/guest-blog/aging-too-mu...

So putting this together with the claim that meditation increases telomere length... meditation increases your risk of cancer? :P

They must be talking about immune system cells, iirc red blood cells don’t have a nucleus.

Yep: “ Peripheral blood mononuclear cells (PBMCs) telomeres length and senescence were assessed”

PBMCs = lymphocytes and monocytes

Well I guess I'll keep scuba diving then.

One of the things HBOT is used for is treating Gangrene.

This article (below) talks about HBOT and is not full of horrifying photos, and I don't recommend you google "Gangrene" if you aren't prepared to look at some really horrifying photos. I am not going to link to any resources on gangrene because I can't readily find any that don't make me cringe and I live with a serious medical condition (and processed accident claims for five plus years), so I am pretty callous about stuff like that. (Someone not taking my warning about medical photos seriously previously: https://news.ycombinator.com/item?id=20680819)

https://www.hopkinsmedicine.org/health/treatment-tests-and-t...

One of the potential causes of gangrene is anaerobic bacteria. And, so, my layman's understanding is that what happens is HBOT forces oxygen into tissues because it's under pressure. It's like some multiple of earth's atmospheric pressure and it can help kill anaerobic infection by exposing them to oxygen in parts of the body that otherwise wouldn't be getting good oxygen for some reason.

I have a form of cystic fibrosis. It is best known as a respiratory condition, but that's not really accurate. It's a genetic disorder and it impairs cell function throughout the body and this impacts some tissues more obviously than others, such as the lungs.

So cystic fibrosis causes a compromised immune system but, like, I spent a lot of years wondering "What does that even mean? Where is the immune system in my body? Which organs are they? How does CF make me so vulnerable to infection?"

And the answer is that "the immune system" doesn't really mean a specific set of organs like "the circulatory system" or "the digestive system" means a specific set of organs. It's just kind of a catch phrase for "how the body protects itself" and it's not really that well understood or explained exactly that happens.

People tend to die really young with CF (like in their 30s or younger) and they very often die of lung infection and treatment of lung issues is a really big part of managing CF.

So one of the things I have concluded is that most likely one of the ways CF impairs my immune function is low oxygen in the body. Oxygen gets used to kill stuff. I think oxygen is an underrecognized part of your arsenal of tools to protect yourself from infection and it's useful against some things that are really nasty, like anaerobic infections, which tend to be ugly, from what I gather.

So I have only skimmed this study. The science is probably over my head and, as if often the case, I am only futzing around on HN because I'm too tired to work at the moment (see the aforementioned deadly genetic disorder). So I am not going to thoroughly read this piece. If I were that mentally focused, I would be working.

But I've skimmed it and I've skimmed the comments here and someone has pointed out this is not about red blood cells, it's about immune cells.

And I will suggest it is plausible that immune cells in the blood would be revitalized by HBOT and "made younger" (that's basically what telomere length gets used as a proxy for) because of what I know about how HBOT gets used to treat certain infections and what I think -- the word think indicates personal opinion, so "don't @ me" as they say on twitter -- what I think about the importance of oxygen to immune function based on trying to understand "So, what on earth does it mean that my immune system is impaired? And how does that work with CF?"

I have always followed your CF posts with interest because when I crash coursed Ayurveda some years back, I remember learning that Ayurveda has no diagnostics for CF (Random Google link: https://saiayurvediccollege.com/ayurvedic-management-of-cyst... ) as it’s mostly inherited and genetically preferred Europeans. So the main source Ayurvedic texts that were centuries old didn’t address that particular combination of symptoms. Or have a name for it.

But we had to start somewhere. So we did a codification of the known symptoms and worked backwards. The goal is to eliminate suffering and take the whole person. That was one of my favorite sessions because we could hack our way to a cure and in a systematic way that was replicable.

Otoh, homeopathy had a protocol for CF mostly because it treats the symptoms one by one and considers the patient as a whole..and not a carrier of one particular disease symptom. Also Homeopathy is relatively new and was discovered by a German physician, Samuel Hahnemann. Personally, I prefer reading homeopathy to Ayurveda because I kept stumbling due to my lack of proficiency w/Sanskrit language. And so I started studying Sanskrit and never did go back to studying Ayurveda in a legit way. But I never forgot the CF discussions. Thanks for your posts and esp the ones educating re CF.

I'm only just now seeing this comment.

A couple of random factoids:

Butter has been really beneficial to me and when I was a lot sicker I sometimes made ghee at home because I tolerated it better.

They are developing a cheap test for CF in India for administering in rural clinics and it's a really interesting approach:

https://www.indianpediatrics.net/feb2019/109.pdf

Yes. But it’s not a definitive test. Hopefully genetic marker tests will become cheaper and widely available.

It's not intended to be a definitive test. The first test usually isn't genetic.

It's purpose is prescreening to decide who to refer to larger medical facilities for more definitive testing. For rural clinics dealing with people where referring someone to a large hospital in a big city involves expensive travel, being able to prescreen helps prevent financial hardship for local families.

Indeed, yes. Not all rural areas have good medical facilities. Many only have mobile services that shuttle diagnostic samples etc.

People please learn how to distinguish between hype & fact.

Facts: senolytics, maybe even epigenetic reprogramming, autophagy, blood transfusions from young to old, genetic editing (APOE4->APOE2. maybe even the icelandic varient someday)

Hype: Anything where oxygen and anti-oxidants are involved. Generally anything that involves oxygen.

do you have references for these claims? thanks in advance.

Can someone explain what this means in layman's terms? What significance does this have?

"Some immune cells have a marker that makes them look younger and healthier after exposure to high pressure, high oxygen environments."

Maybe. If the study is reproducible and yadda.

Were these results reproduced elsewhere?

These results appear to be a partial reproduction / further investigation of "Telomere elongation followed by telomere length reduction, in leukocytes from divers exposed to intense oxidative stress – Implications for tissue and organismal aging" (http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.208...).

This interesting open access paper recently published reports 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 longevity 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.

To be clear, the mechanisms is not high oxygen, but by inducing a fake hypoxia in a hyperoxic environment by varying the oxygen levels during treatment, instigating certain processes associated with hypoxia, but without the damage of real hypoxia. It is not clear that this kind of procedure would be experienced during current treatment regiments using these chambers.

Source for multiple articles where media breathlessly claims that HBOT reverses aging?

"in isolated blood cells"

You could try reading the article next time, rather than having a hot take based on the headline.

"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."

I am wondering how the subjects avoided oxygen toxicity (see https://en.wikipedia.org/wiki/Oxygen_toxicity for example.)

Also, this is half of what needs to be checked. Does lengthening your telomeres have a measurable effect on your health?

From the article - every 20 minutes they used a mask with (normal) air, from what I remember reading it a couple of days ago.

Net/net it's probably safer to put a pint of blood into a hyperbaric machine than a complete human.

They could take your blood, treat it and put it back in. It could have the same regenerative effect as injecting blood from a younger person.

There's no reason to chase immortality. We always exist within the timeline of our lives; the present is not privileged in real physics.

The present is privileged in our real experience tho.

But that's certainly a personal choice though. One day, with enough advances, we may choose to live arbitrarily extended lives.

Speak for yourself.

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