What is Bioelectricity & Its Longevity Implications
Bioelectricity & Longevity; Basics of Bioelectricity
Hi, I’m Aastha, and welcome to Live Longer World, where I interview scientists researching the frontiers of longevity science and write about health & longevity practices.
Sneak-peak update: I recently recorded some fascinating podcasts on how different types of light impact our health, and the effects of dormant viruses on disease. Stay tuned!
Beyond the Gene
In my previous essay Longevity Frontiers Beyond Genetic Medicine, I discussed how biology should be asking questions that extend beyond genes. Biology has heralded genes as kings but what if they do not deserve that status? What if there are important answers buried in information that resides outside of our genes?
Despite the ubiquity of the terms genes and DNA, they are of course not the only important structures in our body. Our body is a bag of cells, organs, tissues, hormones, chemistry, physics, electricity, and many other compounds, the biological names of which will alienate most of us.
Looking beyond the gene means taking seriously some of the other factors that are encoded in our bodies. Last time, I introduced you to one such realm – bioelectricity.
In simple terms, you can think of bioelectricity as what the name implies – electricity that runs through our cells. These electrical signals are shown to have significance in anatomy, embryogenesis, regeneration, wound healing, cancer, and perhaps aging.
However, what does it mean to say our bodies have electricity? No, these electrical signals are not the woo-woo signals a lot of spiritual-esque people will claim they feel. These signals are grounded in physics, or what one may call biophysics.
In today’s essay, I will explain some of the science behind the creation of these electric signals in our bodies.
Bioelectricity and Longevity
You must be wondering why I’m harping on about bioelectricity. Is it just some academic science or can it have practical implications for aging and curing disease? Why does bioelectricity matter?
Deeper understanding of the way our cells use bioelectric signals could have enormous implications for solving diseases. Research indicates that bioelectric signals have significance in cancer, regenerative medicine, anatomy, wound healing, embryogenesis, and perhaps aging.
Let me briefly explain the connection to bioelectricity for some of these, beginning with the deadly monster that is cancer.
Research shows that cancer cells have a different bioelectric state compared to healthy cells. So, could we restore cancer cells back to their healthy state by tweaking the bioelectric signal of cancer cells? This is counter to the current way we treat cancer which is by destroying them. Instead, perhaps we could simply revert cancer cells back to their healthier state, which is what Mike Levin has shown in tadpole models.
Regeneration: Planaria (flatworms) are remarkable creatures that never die. If you cut a planaria in half or even multiple pieces, each piece somehow regenerates the missing parts to form a full planaria again. And not only do these pieces regenerate, but they can in fact regenerate into different shapes, like this 2-headed planaria! Controlling this shape is achieved through tweaking the bioelectric signal of the planaria. Imagine if we could tweak our bioelectric signal to regrow lost limbs and body parts?
Wound healing: Bioelectricity plays a crucial role in wound healing by guiding cell migration, stimulating tissue regeneration, and modulating inflammation.
Aging: It has been noted that as we age, the resting membrane potential of cells gets disrupted. Further, disruption in bioelectric signals has been noted in many hallmarks of aging. So, could we figure out how to tweak the bioelectric state of our aged cells and restore them to a healthy state again?
What does it mean to tweak the bioelectric signal? What are bioelectric signals? I explain below.
Basics of Bioelectricity
Now that you see how bioelectricity can have a big impact on solving disease and boosting longevity, hopefully you will have a deeper appreciation of the field.
It is also helpful to note that most of us are already aware of electric signals that power our neurons. The same electric signals power the rest of our cells, just at slower time scales - milliseconds for neurons vs. minutes or hours for other cells. These electric signals in neurons and other cells is what is called bioelectricity.
In the rest of this essay, I will explain some of the science behind the creation of these electric signals in our bodies. I think it’s much easier to take bioelectricity seriously once you understand some of these fundamentals. It’s also pretty cool to learn about how cells create electric charges. It’s not very difficult to grasp and I’m not going to go into many details. I’ll explain the basics and the terms that are often used so you are familiar with the lingo and can begin to appreciate more of the science behind the electric charges in our bodies.
First, some physics
Feynman once said everything is made of atoms. Our bodies and cells too have atoms. Atoms have electrons and protons. If an atom has a greater number of electrons than protons, it has a negative charge. (i.e. Cl-). If an atom has a greater number of protons than electrons, it has a positive charge. (i.e Na+). So, electrons are negatively charged particles, and protons are positively charged particles. If an atom has an equal number of both electrons and protons, it is net zero charge.
Ions are atoms with a charge. In other words, any atom that has either a positive charge or a negative charge (no zero charge), is called an ion. Ions are fundamental to bioelectricity, as I explain below.
Voltage in cells and membrane potential
Our cells contain different ions, mostly sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+). Cells typically maintain different concentrations of these ions inside and outside the cell, separated by the cell membrane. When you have a difference in concentration of ions on either side of the cell membrane, you get a difference in charges across the cell membrane (on the inside vs. outside the cell).
Any time you separate charges, you create a voltage, which is simply the work needed to be done to push 1 unit of charge from point A to point B. So, when you have different concentrations of charge on the inside of the cell (point A) vs. outside the cell (point B), you create a voltage. In biology terms, a voltage across the cell membrane is known as the membrane potential. You will hear the term “membrane potential” a lot in bioelectricity, so it pays to get familiar with it.
Diffusion
You might wonder: Why is there a difference in ion concentration across the cell membrane? Didn’t we learn about diffusion in chemistry class which says that ions should move from a state of high concentration to low concentration until equilibrium is obtained? If this were the case, there should be no voltage, given that there would be no difference in charges across the membrane. So, why are we still seeing voltage and membrane potential?
Ion Channels, Ion pumps, and Selective Permeability
One of the reasons for the charge differential is because our cell membranes have something called ion channels. Ion channels are proteins that allow specific ions to flow across the cell membrane. For example, sodium-gated ion channels only allow sodium ions into the cell, which means that negatively charged chloride ions might not be allowed inside, creating different charges across the cell membrane. This is the phenomenon of selective permeability where certain ion channels are permeable to certain ions and not others. So, you can say that ion channels block diffusion and create this charge difference or the membrane potential across cells.
Another reason for the charge difference across the cell membrane is the role played by ion pumps1, which are also proteins on the cell membrane. Ion pumps are pumps that use energy from ATP (energy currency of the cell) to move ions in and out of the cell, against the power of diffusion. For example, the sodium-potassium pump (Na+/K+ ATPase) actively transports Na+ out of the cell and K+ into the cell. This pump moves 3 Na+ ions out of the cell and 2 K+ ions into the cell against their concentration gradients, using ATP for energy. This creates a higher concentration of Na+ outside the cell and K+ inside the cell, again creating a difference in ion concentration across the cell membrane, which gives rise to the membrane potential.
Electricity or Bioelectricity
How does all of this give rise to electricity in our cells? Electricity is the flow of charge. We’ve established how we have charged ions inside and outside our cells. In response to various stimuli, ion channels and pumps open and close, resulting in charged ions moving in and out of the cell. The flow and movement of these charged ions creates electric currents, giving rise to the word “bioelectricity.” In other words, the reason we get electricity is because ions are not static, they are shuttling in and out of the cell due to the work done by ion channels and pumps, thereby resulting in the flow of charge or bioelectricity.
Analogy I got from ChatGPT that I thought was useful:
Think of the cell membrane as a dam with gates (ion channels) controlling the flow of water (ions). When the gates open, water flows through, creating a current. Similarly, when ion channels in the cell membrane open, ions flow through, generating an electrical current. The membrane potential is like the pressure difference on either side of the dam, driving the flow of water when the gates open.
Simplified image showing the movement of ions and bioelectricity. Source.
Resting membrane potential
Even at rest, all cells have a voltage difference across the cell membrane known as the resting membrane potential. Recall that this voltage difference or membrane potential is created by a difference in charge across the cell membrane. In most cells, the resting membrane potential is around negative 70mv. It arises due to a tug of war between diffusion and electrical gradients. Let me explain with an example.
Most cells have a higher concentration of potassium ions than sodium ions. At rest, many potassium ion channels are open in the cell membrane, which means they are selectively permeable to potassium ions and favor their passage. Given that potassium ions are higher inside the cell than outside, diffusion causes them to leave the cell, gradually resulting in the cell becoming more negative. At some point, the exit of potassium ions is halted by the increase in negative charge inside the cells. This is because opposite charges attract, and the negative charge inside exerts an attractive pull on the positively charged potassium ions outside. When the diffusion force and the electrical force balance each other, it gives rise to the equilibrium potential or the resting membrane potential.
Tweaking the bioelectric signal
You’ve seen me mention “tweaking the bioelectric signal” a few times in the beginning. This is the analogous version of gene editing for bioelectricity. Now that you understand the basics of bioelectricity, you can begin to see how we can manipulate these signals for longevity and regenerative medicine. For example, you can inhibit the activity of an ion channel or pump and change the ion flow which would alter the voltage of the cell and the electric flow as well. There are other methods for tweaking this signal too, which I won’t go into here. But isn’t it cool if in the future we’re able to tweak these signals not just to have 2-headed planaria or an extra frog limb, but also to cure cancer, and restore lost limbs to humans?
Conclusion
Even though I’m classifying bioelectricity as a frontier field in biology, the research is in fact not new. Scientists have been looking at bioelectric currents in animals, plants, and humans since the 1700s. Luigi Galvani, Giovanni Aldini, Harold Burr, Clarence Cone are some of the early pioneers of this field, and the torch has been carried forward by the likes of Denis Noble, Richard Nuccitelli, Ken Robinson, and of course Michael Levin.
After Watson and Crick’s discovery of the structure of the DNA, the gene-view has occupied center stage in the realm of biology. By gene-level view, I mean biology’s inclination to herald our genes as the most important code to decipher and solve major questions. This is the reason areas like bioelectricity didn’t receive much limelight. However, after decades of research on genes, we now know that they don’t have all the answers, including how shape is formed, and the causes of most diseases. The human genome project was launched with one of the promises being that this will help us map the genes responsible for causing deadly diseases. But this promise was not fulfilled. Not necessarily due to a lack in mapping. But because genetic risk scores are not useful in predicting disease. Biologist Denis Noble says that “what this tells us is that genes are too low a level to see [biological] functionality. We need to get back to network analysis and what we were doing before the genomics revolution.”
Blaming or praising DNA for everything is taking a reductionist view. It’s about time we started reviving areas of biology outside of genes too, if we want a better understanding of the secrets of biology and longevity.
Bioelectricity is exciting not just because it could be an important medium for solving disease, but also because it will expand our repertoire of knowledge, which will bring us one step closer to solving aging.
To living longer,
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Thanks to Benjamin Anderson for feedback on this essay.
I’ll caveat my explanation of ion pumps by saying that although it is the widely accepted theory, it has come under criticism by an alternative theory called Association-Induction Hypothesis, which explains cell functions without the need for ion pumps.
This is a great explainer