Fibre: my 30g per day

High Fibre food is all the rage replacing 'high protein' on every label as it in turn had replaced 'low fat' and 'no added sugar'. 

The recommendation is to eat about 30g of fibre by dry weight each day for optimum gut health mixing soluble and insoluble fibre found in plant based foods. The fibre content is found on all manufactured food labels and AI will get the rest for you using your search engine of choice.

It's actually quite hard to manage 30g of fibre a day and experts estimate 96% of us don't make the target.

Yesterday I did, This is how I did it:

Breakfast: Full english ( sausage, egg, tomato, black pudding, baked beans, mushroom, bacon and two slices of toast) Total 7g Fibre

Lunch: a banana, a packet of peanuts, a bag of crisps washed down with a glass of red wine.              Total 10g.

Supper and evening:

Fish in batter and medium chips with mushy peas and two pints of beer.

Total 14g

Grand total 31g!!  

Plus, this diet was very low in sugar and cholesterol and high in protein, vitamins and minerals.

In all the perfect diet. 

Don't suppose the nutritionalists would approve though. 

Mitochondria: how they interact with the world.

 
Mitochondria can and do 'see' our world.

The effects of electromagnetic radiation (EM) on the bodies of animals and their cells has been investigated
and studied for over a century. From low frequencies to high, the penetration and absorption of EM radiation
in tissues has been of potential concern. This is more so now that we are not only ‘bathed’ in the traditional
frequencies of EM from the slow pulses of the geo-magnetic earth itself and the light from the sun but to the all
pervasive microwave waves of the connected world. 

The focus of interest has been, firstly one of penetration, ie how deep into tissue the EM goes and secondly one of absorption/blocking: does the EM just cause heat ( molecules vibrate more) or does it cause damage (molecules suffer broken bonds)? For example we know about skin damage from UV  light radiation, tissue damage from X rays and the heating effects of microwaves in a microwave oven. So from our perspective of investigation we have EM categorised into:  block; reflect  and absorb with heat and damage being the salient associated words that link with the EM that surrounds us.

This post though is not about the long list of research findings from the above, it is about the interaction of environmental EM with mitochondria. Why mitochondria? Because,  if you have chanced upon these posts before you will know that I regard mitochondria principally as electrical devices; specifically oscillating organic capacitors that use stored charge as the electromotive force to drive biosynthesis.

To an electronic engineer a device of this ilk that holds charge, a charge which varies in magnitude, amplitude and period, is something to be reckoned with. It has an oscillating electromagnetic field so it will inevitably be subject to interaction with EM radiation in complex ways. Terms like field induction, tuned resonances, field switching and so on familiar to the engineer will apply to mitochondria.

Mitochondria are known to interact with penetrating EM radiation at a variety of frequencies.

These are:  
Fields in the 1–8 Hz range have been shown to induce mitophagy (removal of damaged mitochondria) and promote rejuvenation, influencing the electron transport chain (ETC).  the Schumann Resonance at approximately 7.83 Hz, and higher harmonics at around 14.3 Hz, 20.8 Hz, 27.3 Hz;  
An oscillation period of 25 kHz is shown for superoxide; 
Some models suggest cells, including mitochondria, might have resonant frequencies in the 10–30 kHz and 150–180 kHz ranges, though these are less studied.
~125 Hz:

Linked to increased mitochondrial numbers, higher reactive oxygen species (ROS), and changes in

nerve size in some tissues;
 ~250 Hz: A prominent resonant frequency affecting peripheral nerves, leading to inflammation and injury indicators,

and potentially influencing mitochondria indirectly.
120THz  Black Light NIR therapy, absorbed by mitochondria in the 800nm wavelengths

All of the above frequencies are of penetrating EM radiation and its interactions with mitochondria are well documented. Of particular note is the fact that the low frequencies and the high NIR frequency both have their origins in the earth's diurnal rhythms. 
The nature of the mitochondrion has been on a steady journey in the last 50 years.

Lynn Margolis’ persistence and brave insight liberated the mitochondrion from being an

innate structure of the eukaryote cell to that of a once free living organism to now a symbiont working with the cell.

Even so the mitochondrion’s paucity of genetic material kept it in its place subservient to the nucleus’ control.

Even that has changed as the mitochondrion’s ability to retrograde signal with its outsourced nuclear  genes has

become apparent.

Finally, on this journey, i would like to point out that the mitochondrion is not incarcerated,

blind to the outside world. To us we look solid as visible light bounces off our skins but penetrating EM

does not suffer this illusion. Mitochondria within the  body can ‘see’ the environment and due to their electrical

nature they can and do interact with it.

Time to rest, the sun is setting and my mitochondria are signalling time to sleep.  

Silo knowledge and AI

 

Hopefully this post does not come over merely as the grumbling of an old scientist but grumbling it is. My research field was, and my current scientific interest remains in the ageing of mitochondria and their role in senescence.

Anyone who has chanced on my blog posts will know that my focus has always been on the electrical nature of mitochondria and on the entropic nature of the Free Energy they generate. Now, to understand this post you must first understand that mitochondria ‘belong’ to the biochemists,  the molecular biologists, the geneticists (and molecular geneticists), the cell biologists,  the physiologists and even the medics: they all have their particular ‘take’ on mitochondria. All, pretty much nowadays, agree that mitochondria play a central, even THE role in the ageing of an organism. None have any idea what to do about the ageing of mitochondria … and that is despite phenomenal advances in all of their fields in the last 40 years.

At the start of the paragraph above I used words like capacitance and entropy. The former, capacitance,  belongs to the world of wires, charges, voltages, resistance, amps and coulombs. In other words, the world of the electronic engineer. The second word entropy belongs to the world of the physical chemist: enthalpy, entropy, equilibria, Gibbs free energy, joules and statistics (maths!). There is virtually no substantial research on mitochondria as physical chemical electronic devices despite their having trans membrane potentials ( voltages); electron flow (amps);  and capacitance ( farads). That is despite mitochondria initiating cell death when they depolarise ( ie short out to earth ) and losing membrane density as they age (capacitance). There is just as little about the energy mitochondria generate. It is blithely written as Free Energy but unthought of as a hybrid concept embodying enthalpy and entropy. Cholesterol is not mentioned for its ability to increase the dielectric of a membrane; of course not, what’s ‘dielectric’ to a protein molecular cluster specialist?

I am not trying to show what a great polymath I am. Having specialised early in physical biochemistry and later worked as a software programmer and later still worked in the micro-electronics world, all of the above ‘insights’ are obvious to me. No, my point is that if you are a young researcher and mitochondria are what you are looking at then you will be in a silo of one of the areas above in which mitochondria ‘belong’. It is pointless for you  even to know what the electronics engineer or the physical chemist would think as their world is closed to you.

This is a then a grumble about specialisation leading to silo knowledge and research. Nothing new here, but maybe with AI there is a chance that at least the walls of the silos will become visible. Just AI lookup ‘the role of electrical capacitance on the aging of mitochondria’ and you’ll get the picture. 

AI will let you know what you don’t know.

Entropy and Ageing

 

Entropy and Ageing

When I took up my PhD work on the biochemistry of liver mitochondria from old and young rats, my supervisor to be and his senior post-doc both said ‘when we get old we run out of energy so it must be the mitochondria’. They did not actually say ‘duh’ but you felt it.

50 years on, very little progress has been made when it comes to extending our life span: that’s despite astonishing progress in genetic analysis and manipulation. I think (as anyone who reads my posts knows already) that the key to aging is with the mitochondria. The reason is compellingly simple: entropy. 

Entropy is not just another word that simply replaces ‘energy’; it isn’t that simple.

Mitochondria, ultimately generate the vast majority of the chemical-‘energy’ molecule known as ATP, (adenosine tri-phosphate) which can be hydrolysed to form ADP {adenosine di-phosphate) and phosphate ions. The mechanism by which mitochondria do this and the full nature and stoichiometry of the ATP/ADP chemical equation are elaborated to students in details that correspond to whether they are A level students, undergraduate biologists, biochemists, chemists or medical students. What they are not, invariably are engineers or chemists which is a shame as they see things differently.

When you look up the energy yield of ATP hydrolysis it is -7.3 kJ.mol-1,  

That’s usually enough information for most people. It’s energy, end of story. But this is actually a change in energy called Gibbs’ Free Energy and under standard conditions ( pressure temp) it has the symbol  deltaG0

It is a particular form of energy and was ‘discovered’ empirically and formulated explicitly during the steam age, 1873, by Josiah Gibbs. Put simply it was the energy ‘available to do work’ Quite simply engineers and calorimetric chemists noticed that the heat energy released by burning coal never fully translated into work ( eg ‘work’ as in lifting things up)  that a heat engine could do. After fruitless hunting for this energy allowing for heat losses, friction and so on it became a mysterious but fixed fact of life.   Today we know why and all chemistry students are versed in the difference between heat energy, electrochemical energy  and Gibbs Free Energy ( deltaG0) 

I do not have the slightest intention of typing an exposition of dreaded thermodynamics, just to point out that the energy term used above  -7.3 kJ.mol-1, is free energy, and as such contains the term entropy according to the equation: 

ΔG=ΔH−TΔS

In words: Gibbs free energy change is the enthalpy change ( ΔH heat change) minus the change in entropy ( ΔS) at a given temperature(T)

More words: because of this equation,  the key way of looking at mitochondria is less as energy producing organisms but as entropy reducing organisms.

Entropy is a mathematical probability concept, and according to the Second Law of Thermodynamics no spontaneous change occurs without a net increase in entropy. A complex system with a high degree of organisation is in an improbably low entropic state and without a lot of energy input will naturally and completely disorganise itself over time and entropy of that system will increase. 

.

An organism like ourselves, with a vast array of physiological structures and huge storage of complex information from the cellular-genetic to the electronic storage of the brain, requires vast amounts of energy to maintain such local levels of improbability. And as soon as we die, well ‘dust to dust’ springs to mind.

As we age our mitochondria do a sterling job of maintaining a stance against the Second Law but as they fade, if even a little, our system entropy increases and senescence, non-viability of the organism beckons. Tumours have a higher entropy than organ tissue, a demented brain has a higher entropy than a fully functioning one, an arthritic joint has a higher entropy than a healthy joint. The list is endless.

Back to the beginning of this essay: 

The key to understanding aging must be within mitochondria. Its own internal DNA plus that is which it outsourced to the nucleus (for safe keeping from the oxidative furnace that is a mitochondrion) contain the answers. For with Gibbs free energy in abundance they can maintain our low entropy, without it they can't.

As we get old we increase in entropy. 

Capacitance Hypothesis for Mitochondrially Mediated Aging

Capacitance Hypothesis for Mitochondrial Mediated Aging.

The capacitance hypothesis can be summarised as follows:

Mitochondria are electronic devices analogous to electrolytic capacitors. 

As mitochondria age they become increasingly uncoupled ( ie they leak charge) most probably through the mediation of the uncoupling proteins (UCPs). Mild, partial, progressive uncoupling results in a decrease in maximum power, slower recharging (to the required threshold pre-discharge voltage) and a diminished energetic capacity. Full depolarisation results in apoptosis (cell death).

Genetically programmed uncoupling through UCP variations provides a simple basis for a mechanism for determining life span. 

Background: Mitochondria, acting at the cellular level are central both to the aging process and the final onset of senescence. Below are four (uncontroversial) statements supporting this assertion:

• Mitochondria produce free energy, in a chemical form, which is used to drive metabolism and this ‘energy’ decreases with age.1

• Supergeriatric humans (lifespans > 100) when compared to ‘normal’ humans (lifespans  <90) show no differences in nuclear DNA (nDNA)2in whole genome analysis but do show variations in mitochondrial DNA (mtDNA)3

• Mitochondria become progressively uncoupled ( electronically leaky) with age4,5,6: supergeriatrics v normal humans show age-related differences  in so called uncoupling proteins (UCP1-4) which regulate mitochondrial ‘leakiness’.7

• Animals with highly coupled mitochondria ( eg bats, pigeons) live proportionately longer lives than animals of equivalent size that do not ( eg bats v mice 20yrs v 2yrs)11

Fifty years ago my research12 was led by the first of the bullet points - we notice with ageing that we have less energy!. Since that time fifty years ago, technological developments have enabled genome sequencing and rapid structural analysis of proteins but has disappointingly yielded very little progress on the fundamental driving processes of aging. Telomer shortening and free-radical damage13 theories have come and gone in this time, but steadily little by little  the focus has shifted back towards the mitochondrion. So much so that as I write mitochondrial underperformance is being asserted as causal in Alzheimer' s brain deterioration14

Presented here are novel mechanisms for the gradual age-related changes in mitochondrial function, consistent with the facts above, and consistent with experiential changes of aging which are well known to all of us. Additionally, as a corollary, a mechanism for the variation in the life span of mammals is proposed based on a hypothetical determinant mediated by mitochondria.

Mitochondria as electrical devices:

Mitochondria have all of the characteristics of the free-living creatures; that is their biology, physiology, and biochemistry are complex and under the influence of the normal cellular processes from biosynthesis/destruction to reproduction and signalled controls.

I wish to focus here though on one neglected ( I think) aspect of their nature: electronics. This possibility, the electronic nature of mitochondria, came to be a possibility as soon as the transmembrane potential(  ie a voltage, symbol ΔΨ ) was recognised following Michell’s Chemiosmotic15 proton gradient theory over 60 years ago.( For this article protons (H+)  themselves somewhat mythical beasts, are treated  as anti-electrons, analogous to electron holes in the semiconductor world). To date, as far as I can read, the electrical engineers have not had much input into this field, which I hope to rectify (pardon the pun). As a result I am not differentiating in an electronically meaningful way between proton gradients and other ionic gradients. I am just interested in charge separation, electron rich and electron poor regions, or positive ion rich or positive ion pore, separated by a barrier with a known dielectric; it’s all the same.

In this document, mitochondria are regarded primarily as electrical devices, in that they use electrons ( via ion pump proxies) to generate membrane potentials (voltages) and have capacitance ( the ability to store charge) proportional to the surface area and dielectric of the inner mitochondrial membrane. The energy stored by these mini-capacitors is used, in batches, analogous to capacitor discharge, to liberate the Gibbs’ free energy which in turn is used to drive metabolic processes which require it ( for example the synthesis of ATP from ADP and Pi which requires by the way 73 joules of free energy.).

As with capacitors used in the world of electronics, the devices ( mitochondria in this case) have a time-based charging curve, a rapid discharge curve, a dielectric constant based on the lipid composition of the inner membrane, a total capacitance and a charge-leakage profile.

Diagrams:

The diagrams below show a mitochondrion charging through a supply of electrons from oxidisable substrates then rapidly discharging as a threshold inner membrane potential is reached sufficient to generate ATP ( or other phosphorylated nucleotide such as GTP).

The y-axis is related to free-energy, and is comprised of the classical equations linking16 voltage and capacitance to free-energy*. The x-axis is time (T), It can be seen that the charge and discharge of a mitochondrion occurs over time as a near square wave.

The frequency of discharge then determines the energy expended per unit of time, that is it is power(P) output of the mitochondrion. The height of the discharge wave is related to the amount of energy stored

and so is capacitance(C).

Figure 1:

A set of charge-discharge curves for a mitochondrion-capacitor showing showing increasing levels of charge

leakage (uncoupling). It takes increasingly longer to reach the required membrane potential for a given supply

of substrate-derived electrons/protons. Ultimately the threshold potential will not be reached and then

mitochondria will depolarise triggering apoptosis.

Figure 2:

A series of charge’discharge curves as energy is drawn off the mitochondrion in response to demand.

The rate at which work (charge/discharge)  can be done is a measure of the power output of the mitochondrion.

The red lines represent the charge/discharge curves of an older ‘leakier’ mitochondrion.

Less power is available.

Power output.

The diagram in Figure 2 shows the ‘beat’ of a mitochondrial power curve.

Mitochondria are known to oscillate over a range of time periods,

slow  being 4 minutes and faster 20 seconds17.

Mitochondrial cytochromes can also absorb light in the NIR range at about 800nm this is at TeraHz frequencies!18

Capacitance notes: 

For a given supply of substrate-derived electrons/protons the time to reach the required membrane potential depends on the magnitude of the capacitance ( ie amount of energy that can be stored) and the amount  of charge leakage. A smaller capacitance would be an adaptive response to a mitochondrion that is struggling to reach the membrane potential threshold for ATP synthesis.

Possible uncoupling mitigation strategies:

An adaptive response to uncoupling as threshold voltages become harder to reach would involve a decrease in the surface area of the inner mitochondrial membrane in order to reduce energetic capacity but still be viable in the production of ATP. Other mitigating strategies could involve a decrease in the dielectric constant of the inner membrane by changing the lipid composition and/or stimulation of mitochondrial activity by substrate supplementation ( eg acetyl-carnitine, malic acid). Mega mitochondria often obserevd in senescent cell with fewer internal cristae probably represent an attempt to stay viable though in a low power state16.

Ref:

1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18