#1

I thought these articles might interest people.

Dental regeneration: An injectable hydrogel-formulated inhibitor of prolyl-4-hydroxylase promotes T regulatory cell recruitment and enhances alveolar bone regeneration during resolution of experimental periodontitis - PMC
Dental regeneration: Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of periodontitis through metabolic reprogramming - PMC
Ear regeneration: Drug-induced regeneration in adult mice - PMC
Ear regeneration: Supramolecular Polymer Hydrogels for Drug-Induced Tissue Regeneration - PMC

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#2

There are a variety of reasons to think the hypoxic response would be useful in enabling regeneration or rejuvenation, which one of us should probably find the time to do a mini-review on. One notes that there are a few prongs to the pathway, and I kinda thought that the HIF-2 system was the more promising one. It dominates after a few hours of stimulus.

In humans, the literature on therapeutic hypoxia is decidedly mixed ā€“ this concerns me with respect to this line of reasoning. The PHD inhibitor drug class is in clinical use, for kidney failure associated anemia I think. Their clinical effect is via HIF-2 (thatā€™s the one that induces EPO), but of course theyā€™ll raise both in sequence. These are newish drugs, and nothing Iā€™ve seen jumps out in the clinical literature.

#3

The functional stimulus is a reduction in o2 partial pressure rather than static hypoxia.

#4

Iā€™m not sure what distinction youā€™re trying to make?

#5

Hypoxia in the sense of lower than normal oxygen has the potential to be harmful. A reduction in the partial pressure of oxygen from a higher partial pressure to normoxia is unlikely to be harmful. Too high a partial pressure of oxygen for too long is also harmful. Hence it is possible by varying partial pressure of oxygen to stimulate HIF without the harm that arises either from true hypoxia or excessive hyperoxia.

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#6

Yes you can activate those systems by swinging the ppO2 back and forth. Iā€™m not sure this is any safer than just hypoxia. Maybe you have a line on some evidence in this direction? It is more equipment intensive, and the research, IMO, is just as uninspiring.

PHD inhibitors, of course, donā€™t actually oxygen stress the cells, so maybe theyā€™d be safer? Easier, for sure.

#7

I did an analysis on this

It is not ā€œback and forthā€. It is a reduction in PaO2.

#8

Thatā€™s literally back and forth ā€“ to get the falling O2 edge you need to cycle oxygen levels.

#9

Back and forth implies repetition. I think it is best to increase PaO2 for a while, wait then reduce it, but then to wait some time (a day may be best) before doing it again. I dont know of any experiments on this, but i think some time in each state is needed.

#10

This is an interesting video which looks at the link between HIF and mitochondria. I have only watched half of it so far, but it is really good.

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#11

@John_Hemming Any update on this topic? I continue to believe with no proof that a bit of hypoxia is good for my efforts to stimulate my body to stay youngish. Exercise is a part of this of course but also lowering my spo2 (via breathing control) for a few minutes a week is a practice I follow.

Some marketing literature:

#12

No update. I continue to use changes in Partial Pressure of Oxygen. I cannot isolate out the effects of that. It would be gradual like most mitochondrial interventions.

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#13

Iā€™ve recently added the peptide ARA-290 to my peptide intranasal cocktail. It impacts on hypoxia inducible factors and triggers the innate repair response: https://www.sciencedirect.com/science/article/pii/S0163725815000595

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#14

I seem to recall that upregulated HIF-1alpha is a hallmark of some particularly nasty cancers. Multiple myeloma I think is one.
Now, Iā€™m not saying that deliberately stimulating HIF-1alpha will cause cancer. But Iā€™d be doing a lot of reading about it before taking the plunge.

#15

I have done a lot of reading.

HIF 1 alpha is the sort of building transcription factor. Hence it is likely to be part of anything that builds. That includes building muscle and building a tumour.

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#16

ChatGPT says itā€™s safe. What greater authority exists?

ā€œFor hypoxia training, such as intermittent hypoxia training (IHT) or altitude training, the safe level of blood oxygen saturation (SpO2) typically ranges between 80-90%. This is lower than the normal range of 95-100% seen at sea level but is generally considered safe for short durations under controlled conditions.ā€œ

Staying just under 90% for 5 minutes by just shallow breathing takes a will of iron. Anyone here able to go lower?

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#17

I do it the easy way by going high to start out with.

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