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.
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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.
