85 replies to this topic

[Oakman]

Thanks Oakman, that makes sense.  But it also begs the question.  Does a millivolt potential translate to a microamp flow?  

 

No, not really. There's a little thing called resistance to contend with. Try this primer... https://www.abctlc.c...Electricity.pdf

[OP2040]

A nice new Michael Levin video just came out.  A lot of similar ideas to the other lectures he's given.  But I always watch them with rapt interest.  It occurs to me that we can count Michael among those of us that are more inclined to programmed aging.  It's hard not to be when you study embryology and regenerative animals.  The evidence is literally staring you in the face.

 

https://www.youtube....1aLm4Thg&t=302s

 

I'll say it again, my dream is to see something like this applied in vivo to humans, possibly starting with manipulation of the OSKM and other factors.  Sadly, if these geniuses are not there yet, then my dumbass has no chance of making any contribution.  But it's a wonderful fantasy to be a garage biohacker working with this amazing biotech.  It is all quite affordable and it feels like one of those ripe times in history where a major humanity-changing discovery is made by several groups independently but simultaneously.   I think that discovery will be demonstrable in vivo regeneration of a human organ.

[Oakman]

Mind boggling research. It seems initiation of ion channel control voltage potential initiates stem cell (or embryonic cell) subprograms to build almost any body part or tissue from another. Just wow!

[Mind]

I don't think this video has been posted yet. It blew my mind just thinking about how powerful ion channel modulation can be.

 

Bioelectric Computation Outside the Nervous System

[Phoebus]

fantastic over view of the bioelectricity issue here. Really great write up. much more at link 

 

 

 

1. Body parts become damaged with age.  Regeneration will probably be a necessary part of any long-term anti-aging program.  We’ve learned that robust regeneration is available in many invertebrates and amphibians, but it is switched off actively in mammals.  The mechanisms remain latent, untapped, and there are examples of turning them back on.  Bioelectric programming is a new avenue to explore for regaining control of mammalian regeneration.
2. I believe that the developmental clock continues seamlessly into an aging clock.  The same timing mechanism controls both development and aging. If development is under electrical control, then we might find that there are electrical signal networks that trigger aging.  I’ve written to Levin to ask if he is looking into this.
3. Some people in the anti-aging community are also interested in simulating the brain in a computer program, and they imagine that if my brain’s connectivity can be simulated in enough detail, the computer simulation will start to “feel like me”.  For people who believe that consciousness is a function of the brain, and that computer modeling of the brain provides a path to a sort of eternal life, Levin’s work may be sobering. Knowledge and information processing take place not just in the brain but throughout the body, and not at the level of neural circuits but at the level of molecules.
4. The spirit of modern biology is the reductionist spirit of 19th century physics.  Levin argues that we have been remiss in not exploring ways in which living systems are organized from the top down.  I agree.
5.  
6. https://joshmitteldo...-body-electric/

 

Edited by Phoebus, 23 December 2018 - 03:43 AM.

[Phoebus]

 

Volume 95, Issue 5, 1 September 2008, Pages 2242-2253

 

Lipoelectric Modification of Ion Channel Voltage Gating by Polyunsaturated Fatty Acids

 

https://doi.org/10.1....108.130757Get 

 

 

Abstract

 

 

Polyunsaturated fatty acids (PUFAs) have beneficial effects on epileptic seizures and cardiac arrhythmia. We report that ω-3 and ω-6 all-cis-PUFAs affected the voltage dependence of the Shaker K channel by shifting the conductance versus voltage and the gating charge versus voltage curves in negative direction along the voltage axis. Uncharged methyl esters of the PUFAs did not affect the voltage dependence, whereas changes of pH and charge mutations on the channel surface affected the size of the shifts. This suggests an electrostatic effect on the channel's voltage sensors. Monounsaturated and saturated fatty acids, as well as trans-PUFAs did not affect the voltage dependence. This suggests that fatty acid tails with two or more cis double bonds are required to place the negative carboxylate charge of the PUFA in a position to affect the channel's voltage dependence. We propose that charged lipophilic compounds could play a role in regulating neuronal excitability by electrostatically affecting the channel's voltage sensor. We believe this provides a new approach for pharmacological treatment that is voltage sensor pharmacology.

 

PUFA's are beneficial for the body's ability to regulate ion channels. Other fats were not. So this would be like salmon, fish oil olive oil, walnuts, sunflower seeds, etc 

Edited by Phoebus, 23 December 2018 - 05:48 AM.

[Mind]

Based upon Levin's work, I think we need to keep in mind the power of bioelectricity, when evaluating anti-aging treatments. Maybe some things work through the bioelectricity pathway more than through gene expression.

 

It is just pure speculation on my part, but maybe H2S (hydrogen sulfide) produces gains in lifespan, in part because of its possible ability to change membrane potential. After all, SO4 is a common ion found in the body and "used" by cellular ion pumps. Can our cells use sulfates in the same way that some bacteria do, or does extra free sulphur in the body change membrane potential? Maybe.

 

 

[OP2040]

Based upon Levin's work, I think we need to keep in mind the power of bioelectricity, when evaluating anti-aging treatments. Maybe some things work through the bioelectricity pathway more than through gene expression.

 

It is just pure speculation on my part, but maybe H2S (hydrogen sulfide) produces gains in lifespan, in part because of its possible ability to change membrane potential. After all, SO4 is a common ion found in the body and "used" by cellular ion pumps. Can our cells use sulfates in the same way that some bacteria do, or does extra free sulphur in the body change membrane potential? Maybe.

 

I absolutely agree with this.    The great thing about a new theory is that you can reinterpret old data that didn't make sense using old theories, and then find clues about future directions.

 

The part about "what regulates gene expression" is the major point here that you quite rightly bring up.  Gene expression is the most powerful thing known so far that can change the course of the biological fate.  But what controls that gene expression?  Bioelectricity is  great candidate for that for many reasons, not least of which is that it can explain how many different genes and epigenetic mechanisms can be turned on or off to complete some seemingly orderly task or change in life history.

 

I think we will be able to regenerate an organ through gene expression (and epigenetic reversal) quite a bit before we crack the bioelectric code.  But with bioelectricity, things will become much more powerful and effective, as it's modular nature ensures that we can send one signal to accomplish a very large number of downstream signals and gene expression changes.

[QuestforLife]

The part about "what regulates gene expression" is the major point here that you quite rightly bring up.  Gene expression is the most powerful thing known so far that can change the course of the biological fate.  But what controls that gene expression? 

 

The biggest realization for me regarding bioelectricity is that it's not all about genes. Humans share most of their DNA with every living thing on the planet, and most animals produce very similar proteins or combinations of proteins to accomplish similar tasks. And yet we are hugely different in body layout and lifespan. Levine's work making worms grow a head from another worm species  (separated by 150 million years of evolution!), shows that epigenetics or even genetics are not at the top of the tree.

 

I've always known that there must be system (not cell) level signals that somehow suppress cancer and spur regeneration in some animals, but I always assumed they were chemical signals. (Hence why programmed aging proponents always try and point to a controlling source, like the hypothalamus).

 

Don't you just love it when something like this comes along and suprises you?

[OP2040]

Absolutely QfL,

Folks here may not agree with this, but the "Central Dogma" is as good as dead as far as I'm concerned.  There will be no gloating because if it were true then gene therapy could pretty much solve all our problems easily.  Nevertheless, finding the central organizing principle for gene expression is the way forward.  I find it particularly interesting that OSKM seems to work on the whole body, but then there are sub-routines of various orchestrated genes that work for specific organs, and then even lower as well.

 

I really like to use the eye as an example.  So at the highest level, partial OSKM has been shown to induce rejuvenation in many tissues.  Then at the eye level there is another specific set of orchestrated gene expression changes that take place in animals that can regenerate the eye.  Then even lower another sub-set for the retina.  This raises a bunch of questions and shows that whatever mechanism is being orchestrated has to have a memory of the body's pattern at quite a few levels.  In other words, as Levin would say, there is modularity.

 

Bioelectricity seems the most likely candidate for something that can seamlessly orchestrate the number of genetic, molecular and ionic changes that take place during regeneration.  I don't think we need to crack the code before we can regenerate though.  Back to the eye, we can use a brute force method to tune the epiegentic, genetic and molecular state and mimic the same regeneration seen in a newt, for example.  This is much harder but I think it will come before we crack the code of how it is all orchestrated at a higher level.

 

This is all very inspiring stuff, but one negative always sticks in the back of my mind.  Namely, will any of these things work effectively in an organism already fairly damaged from senescence.  There are some studies that show senscence isn't much of a barrier to various types of regeneration, and others that show that there is a period in which damage is so great that regeneration is no longer perfect or fails completely.  After all, we want rejuvenation after senescence has already taken place, or else we are going to help very few people with it.

 

A final note of inspiration.  Whatever the ultimate mechanism, I think there is a connection between all the types of regeneration we see, whether it be germline, hibernation recovery, injury induced, etc.  The fact that it has occurred so many times in nature means that once we figure it out, it will become a rather mundane affair that is very easy, low cost and faithfully replicated.

[Oakman]

When I was a kid, at one point I was interested in auras, around plants, hands, people. At the time, and probably still, it was an idea before its time, although in light of new information such as new discoveries in bioelectricity and quantum physics, it may be time to revisit these old concepts and see if they can shed light on new discoveries. For example ...

 

http://www.biofieldg...human-aura.html

 

"Scientists and researchers today all around the globe have confirmed that the matter which appears to be solid in reality is NOT TRUE. This solid looking matter is actually made up of pure energy which is vibrating at a specific frequency which gives matter properties like shape, size, texture etc. These solid looking objects like a pen, book and even the molecules, atoms and cells in our bodies for that matter are actually made up of vibratory energy particles called electron, protons , neutrons and further more tiny particles. So when these particles vibrate in their nucleus, a small electrical impulse is generated in our body and according to the famous law of physics “When there is a electrical field around a body, a magnetic field gets developed automatically”. So the tiny electrical impulses in our body results into the formation of a magnetic field around our body which is actually know as the AURA- electromagnetic field of the body. Since everything in this universe is made up of the same constituent particles electron, protons, neutrons etc that means EVERYTHING HAS AN AURA.  And if we keep on expanding these so called elementary particles we reach a point where we find nothing but pure energy vibrating at the very essence of these solid looking objects. Everything in this physical universe is nothing but energy which connects to everything in the universe."

[Mind]

 

 

This is all very inspiring stuff, but one negative always sticks in the back of my mind.  Namely, will any of these things work effectively in an organism already fairly damaged from senescence.  There are some studies that show senscence isn't much of a barrier to various types of regeneration, and others that show that there is a period in which damage is so great that regeneration is no longer perfect or fails completely.  After all, we want rejuvenation after senescence has already taken place, or else we are going to help very few people with it.

 

Good thing that is seems likely we can clear a lot of senescent cells from the body.

[OP2040]

It's unfortunate that controlling these higher-order mechanisms seems quite a bit further off than say, senolytics.  But at least it's being acknowledged and worked on.  We could go on a lot about the philosophical implications of all this, one of which is that the much-hated "vitalism" that hasn't been much talked about since Bergson, will be greatly vindicated, although I'm sure most will stubbornly resist the idea that bioelectricity has anything to do with vitalism.  It will also boost the historical significance of Galvani, who was way, way ahead of his time, but also similarly shamed historically.

 

Anyway, here as a quasi-related article on how genes are really not as important as we thought, and how the "central dogma" is going down in flames.  There are a number of ways in which the central dogma is important to this discussion.  The most important point in that regard is that genes are not the determining factor in any kind of regeneration or rejuvenation.  Genes most just code for proteins, and many genes are often acted upon by "something" higher-order, to accomplish a biological task.  Bioelectricity is a great candidate for that "something".  We absolutely need some minimum set of genes to do that coding, but Levin's work has shown that a huge, chaotic mess of genes can work just fine for total regeneration given the imposition of that "something".  That is the most amazing observation that has come out of this research so far.

 

Also, it's often quoted to the point of cliche, that humans share most of their dna/proteins/etc. even with radically different, basic animals.  And even when not shared, there is almost always a homolog.  So, it should be really obvious that genes are not determinant in-themselves, rather gene expression changes, activated by "something".

 

Genes are thus stripped down of their oversized importance, and what they are seemingly left with aside from protein coding is inheritance.  Admittedly, this is a pretty big role to play, and I haven't read anything about a connection between bioelectricity and inheritance...............yet.

 

https://www.quantama...mplex-20190108/

Edited by OP2040, 11 January 2019 - 02:29 PM.

[QuestforLife]

Absolutely QfL,

 

This is all very inspiring stuff, but one negative always sticks in the back of my mind.  Namely, will any of these things work effectively in an organism already fairly damaged from senescence.  There are some studies that show senscence isn't much of a barrier to various types of regeneration, and others that show that there is a period in which damage is so great that regeneration is no longer perfect or fails completely.  After all, we want rejuvenation after senescence has already taken place, or else we are going to help very few people with it.

 

 

Are you sure it's not the other way around? I've read studies where senescence is part of de-differentiation, to the extent where I wonder if it might not be an intentional part of the process of healing and rejuvenation. This might make senescent or near senescent tissues easier to rejuvenate. The downside might be that a experimental rejuvenation therapy might generate a lot of senescent cells to the extent that inflammation might become dangerous to the patient. Still lots to discover here...

[OP2040]

Are you sure it's not the other way around? I've read studies where senescence is part of de-differentiation, to the extent where I wonder if it might not be an intentional part of the process of healing and rejuvenation. This might make senescent or near senescent tissues easier to rejuvenate. The downside might be that a experimental rejuvenation therapy might generate a lot of senescent cells to the extent that inflammation might become dangerous to the patient. Still lots to discover here...

 

Sorry for the confusion.  I just meant senescence as in the general process of aging, not just senescent cells.  I agree that senescent cells seem to be part of an overall signaling process, just like ROS.

 

All of the hallmarks seem to be quite a bit intertwined.  Assuming it were cheap enough to do, it would be great if all the hallmarks were tested for any one intervention.  You might find some interesting relationships between them, like if some are more important in the hierarchy. 

[OP2040]

Hi folks,

 

The Levin lab continues to do great work.  They come out with papers at a fairly decent clip so no need to post them all.  However, here is one fresh off the presses that offers much more insight than usual:

 

https://www.ncbi.nlm...pubmed/27372644

 

 

What they purport to show here for the first time, at least in Planaria, is that bioelectric signals come before the gene expression changes during regeneration.  I was already convinced that gene expression is the key factor in any type of animal regeneration.  It has been documented for many organs that the difference between an animal that can regenerate and us is not down to the genes, proteins or other bits and pieces.  These are all the same.  The major difference is simply whether certain genes are turned on or off.

 

So that is already a pretty revolutionary insight.  But add to that the idea that bioelectric signals come before, and potentially cause the gene expression changes necessary for regeneration, and we have a complete biological game-changer.  It starts to look like bioelectricity is how memories of patterns are stored, and when that field is disrupted, it starts a while cascade of gene expression changes, which then direct the bits and pieces way, way downstream.

 

We probably will be able to engineer the correct gene expression changes with CRISPRi long before we know enough about bioelectricity.  But once we do know enough, the bioelectric route would be orders of magnitude more effiicent and less invasive.

 

[Oakman]

Couple of fairly astounding finds re:bioelectricity. We are just part of a big circuit called life.

 

Amino acids allow bacterial ‘nanowires’ to conduct electricity

 

A team of researchers in the US claims to have found clear evidence of a microbe that conducts electricity along protein filaments, just like a metal. By showing that aromatic amino acids are critical to both the electrical and respiratory activities of Geobacter sulfurreducens, the group claims to have unequivocal proof that the bacteria funnel electrons up and down “microbial nanowires” using the exact the same principles as the synthetic organic materials used in electronics.

 

 

Conducting research: Exploring charge flow through proteins

 

"If you had told me that proteins would be good circuit elements 5 years ago, I would have laughed at you—that's ridiculous," Lindsay says. His skepticism however, soon gave way to surprise: " We discovered a few years ago that a protein involved in sticking cells together, with no known electrical function, conducted like a beautiful wire if connected to electrodes by the small piece of protein it had evolved to recognize. This was a big mystery to us, and the present study was designed to see if this was a general property of any randomly-selected protein. It turns out to be true: all the proteins we have tried, connected to electrodes by means of the specific molecules they recognize, make almost perfect molecular wires, though we are far from understanding why this is."

Read more at: https://phys.org/new...oteins.html#jCp

[Mind]

Is this evidence of a deeper level of biological programming than DNA? The brain cells organized and grew into a mini-brain. https://www.prospect...-a-second-brain

[Oakman]

"I am just one expression of that meta-me. My boundaries of personhood feel just a bit fuzzier than they did."

 

Perhaps this reflects the quantum nature of the world. Your transcription programming could develop in many ways, but one of an infinite number is bestowed on you at conception in this space-time.

[Mind]

I am unsure if this is relevant, but it reminded me of this thread and the potential of a more conserved basic regulator of cell behavior (other than genetics): https://www.scienced...91107122638.htm

 

"We previously thought that transcription factors drive the process that determines whether a gene is expressed and subsequently translated into the corresponding protein. Our new results show that transcription factors may be more analogous to being the memory of the cell. As long as the transcription factors are connected to a gene, the gene can be read (turned on), but the external signals received by the cells seem to determine whether the gene is turned on or off. As soon as the transcription factors are gone, the cells can no longer return to their point of origin,"

 

 

[Oakman]

Thanks Oakman, that makes sense.  But it also begs the question.  Does a millivolt potential translate to a microamp flow?  A quick google search shows that 1 Millivolt/Ohm converts to 1000 microamperes, The reason I'm interested is because I'm used to reading about the potentials, not the flow.  And it's also been noted that the electricity we often use in everyday situations is much too powerful for any of this.  So it looks like 500 microamps is in a range that makes biological sense.

 

A little basic electricity gives the answer. Resistance (to flow) is what constrains electrical current (electrons). Voltage is what tries to 'push' electrons (current) through a resistance. Some examples can help here...

 

With a very high resistance, and a very high voltage (say 10,000 volts) you only get a small current flow according to the equation, Amps= Volts/Resistance. For example to determine in a certain case: Amps = 10,000 volts / 10,000,000 ohms equals .010 amps or 10 milliamps. This can cause a bit of pain and discomfort in the body. Reduce the voltage to 100 volts with the same resistance and the current flow is .0001 amps or 100 microamps. Not dangerous, barely (if at all ) noticeable.

 

And so forth. To your question, "Does a millivolt potential translate to a microamp flow?", it can under certain conditions of resistance. So, for example, Volts = Amps x Resistance, or V = A x R. Therefore if we have .010 volts (10 millivolts) and a .01 ohm (resistance) we get Volts = .01 x .01 = .0001 or 1 microamp current. 

 

You can vary these three; volts, amps, resistance and get any result you want. An extremely low current at high voltage is what allows people to touch a van de graaf generator (VDG) and have their hair stand on edge, but feel no pain, for example.

 

"ELECTRIC CURRENT: a tabletop VDG produces an electric current below 100 uA (microamperes), which is about ten times smaller than a human is able to feel. If you lick your fingertips and touch them to the terminals of a 9v radio battery, the level of current in your fingers will be much higher than that produced by a VDG machine. As far as constant currents go, a 9v battery is more dangerous than a VDG."

 

http://amasci.com/emotor/safe.html

 

In humans, the body works with electricity like this, but at a cellular level the potentials vary greatly.

 

https://www3.nd.edu/...of the Body.pdf

 

"Resting membrane potential is approximately -95 mV in skeletal muscle cells, -60 mV in smooth muscle cells, -80 to -90 mV in astroglia, and -60 to -70 mV in neurons."

 

http://oer2go.org/mo...1255/index.html

Edited by Oakman, 09 November 2019 - 03:38 PM.

[MidwestGreg]

Bioelectricity is very real. I'm a physicist and I can attest to its realness. There are books yet to be written on this subject. What may sound like quackery could be real. I've seen some strange things happen first hand with human bioelectricity.

​Rocket - I would also like to hear more about your experiences. If you are not comfortable discussing it here, would it be possible to point me to a site to learn more? Thanks

[aribadabar]

Guys,

 

I just came across blood electrification and wanted to get your take on this vector? Snake oil or solid science?

 

[dalack]

Darpa seems to be interested.

https://now.tufts.ed...d-wound-healing


https://onlinelibrar.../advs.201600527

Edited by dalack, 06 May 2020 - 12:24 PM.

[Mind]

Just another mind-blowing paper from Levin's lab: https://medicalxpres...tric-drugs.html

 

This is similar to other things his team has done and probably familiar to most people who have read this thread or watched some of the videos.

 

If I was a programmer with some knowledge of biochemistry, Levin's lab is where I would want to be.

 

I am not sure the best way to explain bioelectricity regulation as "upstream from genetics" to lay people. Maybe: A group of programmers/engineers (our trillions of diverse cells) get together to write a program/blueprint (DNA) for a car (human body) to drive them around. They all know the program, which is distributed throughout the car, so any one of them, or group of them, can fix things that go awry in any part of the car, from anywhere they happen to be located in the car.

 

Many plants (and lower organisms) seem to have this distributed "sense" (like Levin has revealed in his work on amphibians). We have a Jade Plant in our house. Clip off a leaf from any part of the plant, put it in water and it starts growing roots, and in no time you have a whole new plant.

Edited by Mind, 29 May 2020 - 07:21 PM.

[kurt9]

Its been my impression that the role of electricity in biology is more energetics rather than informational. Clearly the electron transport chain is the most fundamental example of this. Similarly, the ion-channels along the axioms in nerves is for energy transport as well. I am skeptical of any claims of electricity playing an informational role as opposed to energetics in biology.

 

 

Edited by kurt9, 29 May 2020 - 06:58 PM.

[QuestforLife]

Just another mind-blowing paper from Levin's lab: https://medicalxpres...tric-drugs.html

I am not sure the best way to explain bioelectricity regulation as "upstream from genetics" to lay people. Maybe: A group of programmers/engineers (our trillions of diverse cells) get together to write a program/blueprint (DNA) for a car (human body) to drive them around. They all know the program, which is distributed throughout the car, so any one of them, or group of them, can fix things that go awry in any part of the car, from anywhere they happen to be located in the car.

Interesting that the drug patch they used wasn't even specific to fixing problems in the brain, just problems..

It's like the body is an electrical circuit and Levin just connected a battery.

[Mind]

Interesting that the drug patch they used wasn't even specific to fixing problems in the brain, just problems..

It's like the body is an electrical circuit and Levin just connected a battery.

 

If I had to analogize it, I would say "Levin connected a powered USB cable". It seems he is manipulating the electrical/ion signalling between cells, in a "programmatic" way, not just providing straight up "energy". If I interpret his papers (and videos) correctly, he claims to be manipulating a cellular-life program that is upstream from genetics.

[Mind]

Here is a book that seems to be related to Levin's work. https://www.goodread...nguage-of-cells

[lukas_93]

after watching this presentation by Levin 

 

It seems like you could potentially run your own experiments, since they open sourced their tools: 

 

EDEn - Electroceutical Design Environment 

http://eden.pharmamatrix.ca/

 

BETSE (BioElectric Tissue Simulation Engine) 

and https://gitlab.com/betse/betse