Neoteny, the man-child

Neoteny is the retention of juvenile traits into adulthood. Humans, homo sapiens, that is to say have extreme neotenous traits when compared to their great ape cousins and homo ancestors. They are well known, but just to restate some of them: hairless bodies ( or nearly so); flat faces; large head to body proportions; large eyes ( again relative to head and body); a lower degree of  sexual dimorphism; an extended childhood with traits like explorative behaviour conserved into adulthood (even for life); increased brain plasticity … and many many others. Finally, observable to even the most casual looker, neoteny is ongoing. Adolescent behavioral traits are often maintained into early thirties and pre-adolescent gender fluidity is increasing accompanied with falling birth rates as pre-reproductive phases encroach on post-reproductive phases of life.

Humans are changing, we could say ‘evolving’ but we need to update our school-age Darwinian play-book to make sense of this. When I taught ‘evolution’ in senior biology classes I relied on a paradigm that was and is ‘true’ but as one would expect not the whole picture. Evolution according to this paradigm and runs like this:

Our genes (genotype) control our appearance (phenotype) and by extension all our physical and mental attributes. Variation in our genes either through random mutation or the natural pack-shuffling of sexual reproduction produces  variation in the next generation. Interaction of these offspring with the ever changing environment determines how well they thrive and live to successfully reproduce. This is the fate of the  ‘survival of those most fitted to their world’ and by extension so  their genes will be passed on.

Two major discoveries nuance this piece of well tested logic. The first is the fact that most genes are highly conserved. That means they don’t change. For example the gene for a fly’s eye is the same as that of an octopus as that of a human. But these creatures have very different eyes! 

The second fact is that epigenetic changes ( DNA outside of the nucleus not in theory passed on in reproduction) authored by interaction with the environment can and do get incorporated into the genome which is then passed on. This is called neo-Lamarkianism after the soviet agronomist who believed ( disastrously in this case) that the effects of the environment directly shaped the genome.

What we now appreciate is that it is the activation and temporal expression of control genes that created the bewildering variety of life, not the library itself. This brings me to the central point of this post. We are now led not to the library of genes but to the importance of the interface of the organism and the world. The interface is where the integration and communication with the world happens.

The Descartian dualism of the past has always been a hindrance to modern science where we are special creatures observing objectively a world which we can interrogate. Physicists have long overcome this illusion but environmentalism is a newer discipline and is only just catching up.

We interact with our environment. We have senses ( which misleadingly can enhance dualistic approaches ) just for that purpose; we acquire epi- genetic material from a kaleidoscope of viruses and vaccines that infect us and even, deep within bodies, our mitochondria inside cells sense and react to NIR (near infra red) light from the dawn and dusk sunlight.

It’s not rocket science to realise that if our interaction with our world results in a small change in control genes then our own phenotype will change too … and rapidly, not Darwinian generationally. Anyone who has seen a now old video of young late-adolescent orangutans will not forget the recording of the favored youth among many candidates ( selected by the female on whatever grounds)  metamorphose into an adult challenger complete with cheek pouches, just on a high-level environment signal aka the females’ approval. 

It is possible (and it is my opinion) that the neotenous tendency of our control genes, the very genes that produced the man-child that propelled Sapiens to its technical tool making dominance, are on the march again. The signals from the environment ( maybe TV/Smart Phones) have awoken them. This time this peculiar trait may well bring about our reproductive end and explain a reverse coin of neoteny that is early onset cancer. On the upside the boost in creativity may give birth to a very different version of ourselves, know colloquially as AI.

NAD+ solves the aging puzzle

 

It’s fifty years since I completed my PhD on the biochemistry of mitochondrial aging. At that time, interest in the subject of aging was minimal. Fast forward to today and the biochemistry of aging and the role of mitochondria is centre stage. One can feel the breakthroughs coming very swiftly as pennies are dropping.

In the 1970’s, the centrality of mitochondria in the process of aging was based on a very simple premise: in senescence you run out of energy and it’s mitochondrial bioenergetics that generate that energy.  Mitochondrial dysfunction in aged cells reduces the availability of chemical energy changes (Gibbs energy (∆G)), which means that the low entropic state that is a healthy living cell gradually increases until it fails.

Today, the fundamental truth above is fully appreciated

and can be integrated with many of the puzzles of aging..

Fifty years of results from genetic activity (genomics) ,

free radical theories of aging and metabolic signalling

can be reconciled into a bigger picture.

In addition, the disparate macro effects of obesity,

lifestyle, and diet on aging now all slot into place.

The key link is the new darling of the anti-aging world

… NAD+ and its aging-linked nemesis NADH + H+.

It’ll be tricky to explain in readable prose,  but I will try. 

The small molecule NAD+  decreases within cells with age. It is the oxidised form of a class of molecules called nucleotides. NAD+ is used up, consumed, in various biochemical processes and with age decreases despite being synthesised from scratch and carefully scavenged and recycled. It is also not easily supplemented.

The  important thing about NAD+ is that it is able to accept electrons from hydrogen (H). These electrons come from the metabolism of food such as fats, proteins and sugars. NAD+  then becomes NADH + H+ and this molecule feeds electrons into the mitochondrion’s complex system of enzymes to produce chemical energy. It’s the ratio of NADH/NAD which is creating excitement in the aging world. Basically if NADH is much higher than NAD, ie the ratio is bigger than it should be, this is a very bad thing in terms of aging. 

The reason why a high NADH/NAD is bad is because the mitochondria, unless very active energetically, cannot handle the amount of electrons that can be provided by excess NADH. Long story short, depending on how much the oversupply of electrons is,  a burst of highly damaging free radicals is produced. Reactive oxygen species (ROS) as they are properly called, are known to increase with age and to be responsible for a lot of the cellular damage associated with aging. And, as is well known, we are urged to eat healthy foods high in anti-oxidants to prevent such damage.

Clearly then, since NAD+ reduces with age any increase in the size of the pool of NADH will make things worse. This is where 21st Century humanity come unstuck.

It’s a fact: modern humans in the developed countries are largely physically inactive, well fed and graze feeders.

This means that they have no spare capacity to store dietary sugar as glycogen. Sugar which is not needed for activity, cannot be stored because the stores are already full. Modern diets high in glucose syrups, maltodextrins, lactose, fructose and potato starch are effectively diets of sugar. The sugars must be metabolised within cells. They cannot hang around in the blood. The metabolised sugars are then either stored safely as fat or broken down further and their hydrogen passed to the mitochondria for oxidation. Here is the first source of hydrogen over supply together with the link to diet and obesity. Inactive bodies have inactive mitochondria. The stimulation of mitochondrial metabolic activity from baseline tickover is signalled in an array of ways, foremost amongst which is physical activity. The mitochondria are not ready to receive hydrogen/electrons, ie not powered up. They will however accept the electrons, but with accompanying disastrous free radical production as the electrons react in an uncontrolled way with oxygen. Here is the second driver of oversupply of hydrogen.

As a consequence of the above, ( viz UPF rich diets, grazing eating and sedentary living) the ratios of NADH to NAD become high; too high. This state risks massive spikes in free-radical damage which lead to premature aging and early cancers. 

As I said at the start of this post, the biochemists now know what is going on. What will be the result? A new pill? Or a lifestyle change? Your guess, but at least we are close to knowing aging now.

Creatine Supplementation and Aging Mitochondria

Creatine and aging mitochondria.

Creatine supplementation and aging mitochondria.

Implications of the capacitance hypothesis in aging mitochondria.

As we age we run out of energy. An everyday colloquial, universal refrain which brooks no exceptions. What exactly we run out of is more difficult to pin down. This post hopefully will give clear picture of what it is. It is inspired by a couple of contemporary trends: batteries and creatine supplements. Or put another way, energy storage.

A while ago I described in a previous post (Mitochondria, oscillators and broadcasters?) an electrical model of a mitochondrion. 

It was very simple: electrons were supplied in variable amounts to a capacitor which then discharged through a solenoid coil when it reached a threshold voltage.

The supply of electrons was regulated by a light dependent variable resistor; the capacitance of the ‘mitochondrion’ could  be varied; the activation of the solenoid in reaction to the discharge of the capacitor represented a transduction of energy into a form that could do work and finally a ‘bleed’ variable resistor simulated the loss of charge by a ‘leaking’ aged mitochondrial membrane.

All of the above is meant to be an analogy, in purely electrical terms, of a real mitochondrion receiving electrons from its substrates, charging the inner mitochondrial membrane and transducing its energy into the likes of ATP. 

 

As described previously, what shocked me after I chose to output to a sound file in Sonic.py, was the thumping beat of the oscillating charge and discharge, and how this sound changed its period as the ‘leak’ was increased until it collapsed into a single tone. 

Recently I sketched these results which are shown below as how I imagine it occurs in actual mitochondria.

It can be seen that as a mitochondrion becomes more prone to losing charge, leakier’, as is well known to happen in senescent mammalian cells, then the charging curve takes longer.

Clearly the next ‘dump’ of energy cannot happen until the threshold voltage for the individual as been reached. 

(In a cell containing thousands of mitochondria we are not looking at an individual but a population but nevertheless the principle will be the same for old and young mitochondrial subpopulations within a cell.)

Running out of puff = running out of Power

The power output of the mitochondria is the rate at which free energy can be drawn off, the unit is Joules per second,  commonly known as Watts. ATP the ‘free energy molecule’ can provide about 58,000 joules per mole of ATP.

From the graph you can easily see that although a fully charged mitochondrion can provide the same energy whether old or young, the longer it takes to recharge, the lower the power output.

Creatine and Batteries

Creatine is a very popular food supplement. It has been used by strength athletes foe many years but now is finding great favour as a sleep aid and calmative. Creatine stores are like batteries. Many homes nowadays have batteries to store energy in off peak times to charge their EVs for action later or indeed their heating systems. Creatine stores are analogous in that they are able to store chemical energy from ATP as Creatine phosphate which they can very rapidly give back to the ATP on demand.

Aged humans often have sleep problems. The brain needs a lot of ATP energy, 24/7. This is provided classically from glucose and ultimately by mitochondria. If the baseline power output of mitochondria in the brain is low then they will not be able to stay in sleep-mode. They will have to up their output to the minimum required by the brain. However if you have invested in a battery, then they can be supported. In fact although most creatine phosphate is stored in the muscles for instant action, five percent is stored in the brain.

It is likely that creatine supplementation in general is a good ‘battery’ support for aging mitochondria in many active tissues. Natural sources are fish, meat and dairy ( herring being foremost) but to get large amounts you need the white powder supplement. Given the above post it will be interesting to see how supplementation pans out long term.

 

The Wagyu Generation, Gen W

The Wagyu Generation

This post could be also titled GenW or ‘Ways the USA’s agro-biz makes us sick’ but that latter remark would be to invite the inevitable lawyers’ letters … so Wagyu it is.

I have for a good while now noticed that a lot of folk under 25, especially adolescents and children look oddly ‘inflated’.  Not fat in the way older people have a protruding abdomen and various mounds and flaps of subcutaneous adipose tissue, but softly pneumatic. Additionally, also noticeable is that sexual dimorphism is less evident thus adding to their unique appearance. 

If we were cannibals (or if they were cattle) they would, I think , be good to eat with tender, heavily fat-marbled meat and pale fatty soft livers. Yum. Wagyu.

(as an aside, quite possibly if they were actually cattle, EU regulations may have something to say about how they are kept cooped up in small rooms an overfed on high calorie junk food)

The ‘wagyu’ generation as I will refer to them is real. In previous posts I explained already how we know UPFs increase intramuscular fat ( ‘UPFs give you Wagyu Thighs’), why fructose excels at creating fat deposits even if you exercise (‘Fructose makes you very fat’) and why Soya’s phyto-estrogens contribute to declining birth rates in all  developed countries (‘The Future is Trans’). Read them if you want more details. Below is my conclusion in the simplest terms:

This largely sedentary generation’s diet has been fatally corrupted through its levels of fructose, soya  and CLAs ( conjugated linoleic acids).

1. Fructose (or fruit sugar as it is often called) bingeing started with the availability of fruit juice concentrates. Overproduction of citrus in the US plus good marketing leveraged its Vitamin C content and the rest is history. Now fruit derived concentrates are everywhere. Later, as a result of an analogous overproduction of corn in the US, we have high fructose corn syrup as the main sweetener in nearly all cakes and baked goods.

2. Soya is in so many products I will not enumerate them.Soya milk is ever popular and, finally, the marketeers have struck gold with the high protein fad leveraging soya’s high protein content. Overproduction and reliance on soya beans in the US has.. oh we’ve done this before!

3. Finally, Conjugated Linoleic Acids used by farmers to make wagyu beef are plentiful in wheat and dairy ( think Latte and Pizza) leading to a plethora of coffee shops and pizza outlets. Overproduction of wheat and milk in the US ...

So there you have it. The wagyu generation. Fed on food no one needed or wanted, marketed brilliantly to unsuspecting dupes.

At least the farmers made a profit but at your cost/

Social Media's evolution was inevitable-repost from 2018

Please stop teaching psychology

…  or why Darwin and Dawkins are always right.

This article from 8 years ago seems more relevant now and introduces the

idea of a psyhcological-niche obeying the laws of natural selection evolution.

It could also be titled 'don't blame the techies for your mess'

In my role as a Computer Science teacher I needed to prepare some classes for my students about social media. It’s in the syllabus, it was in the news; Facebook and data harvesting being the media’s ‘mot du jour’ . So I ‘did’ SnapChat, Instagram, Twitter, WhatsApp and Facebook. But what struck me was I hadn’t got much to teach my students. The computing stuff was old and simple; TCP/IP comms, a bit of up to date compression and optional encryption; it was a bit all 1990. As a techie, its core was of little/no interest.

So who is interested in this stuff? I don’t mean the users of social media, obviously they are interested, but which ‘gods’ are watching over these applications?

A few years ago I looked at the UK graduate stats by subject. Without too much dissection it is safe to say that psychology graduates rather outnumber computer graduates by a factor over tenfold and much more than that if you only count females. Psychology is now rather hidden in the official stats as it is bundled into a category ‘subjects allied to medicine’. I suspect it was becoming embarrassing to discover how many budding ‘shrinks’ were in the pipeline.

So, take a bit of simple tech ( remember MS Instant Messaging, Skype?) add a generation of business and psychology graduates and what do you get?  Social Media, the love child of a million psychology graduates looking for a job in selling anything from plastic frogs to conspiracy theories.

What does psychology qualify you for with regards to selling? … manipulation is the obvious answer. However to manipulate effectively you have to know your target. To know your target as an individual does not scale well, so called micro- targeting works really not on individuals but  on quasi-homogeneous groups. It’s so much more than your browsing history and postcode

Here is how it’s done. Below is a homage to the great Richard Dawkins, author of the Selfish Gene and creator of the gene’s abstract replicator, the meme.

Social media platforms have something in common, the ability for a communication to be approved by a group or deprecated; more familiarly ‘liked’ or ‘disliked’. This is profound and if we borrow the logic and terms of evolutionary biology we can do the following steps:

A post, (maybe a picture/movie or an opinion) gains in value if it is liked and loses value if disliked. The direct analogy is with a selection pressure deriving from an environment. So an ecological niche corresponds to the social media group ( It may be big or small and highly specialised or less so just like nature). Being ‘liked’ is a bit like having the right beak to open the local nuts.

If we regard a post not just as one post, destined to survive or die, think of it as an instance of the user themselves; an abstract organism that is made manifest via it’s posting-phenotype. A subsequent post is actually a reproduction from that user. It’s not the same post obviously, but it inherits properties from earlier posts. ‘Liking’ a post makes it fitter to survive in its environment and subsequent posts will then inherit characteristics that caused it to be liked. Ideally being ‘liked’ even more becoming a more valuable property of the organism.

Vice-versa for dislikes you may think but not quite so. Consider a group of say 20 folk, a given post you notice is liked by 15+ on average, but consistently 1-3 dislike it. They do not have a selection pressure, they simply get ‘unfriended’ or whatever the term is in the software. If 15+ quite often don’t like your post then you must change or migrate out of the group. The latency built into the system increases with the size of the group but the principle remains true.

However you do it within your ecological nice ... psychological niche is the right phrase, ‘fitness’ to survive reflects an accretion of adaptations. And as in Nature, the drive is towards homogeneity, but without sex to stir the pot or an unyielding indifferent environment to provide external limits to change. A psychological niche is user-defined and so has no limits only homogeneity.

Now we have it, a group occupying a psychological niche can be characterised by the watching ‘gods’ through a process called data-harvesting. Once you know the psycho-nice well enough you can manipulate it, sell to it.

So that is where all those psychology graduates went. All they demand from the techies are more tools to harvest data from daft quizzes, geospatial data, face recognition and so on. Then it’s back to the ‘how the brain works’ books on behaviour and job done.

Micro-targeting bad examples: don’t try to sell ex-Nazi era thermal underwear to folk living in sunny Israel nor books on liberal democracy to an ISIS whatsapp group. They won’t buy.

So don’t blame the computer scientists for the evils of social media, the tech is not rocket science or even new. Blame an army of psychology graduates looking for a job who took our IP protocol and made a monster. All of this by the way is fully predicted by Scott Adams in his 1999 book The Dilbert Future: “Thriving on Stupidity in the 21st Century”. 

Statins and Mitochondria update.

 

I've posted about the effect of the cholesterol synthesis blockers known as statins on mitochondria before. This week though a couple of updates on the national news seem worthy of comment.

The first was a a publication from the University of Columbia detailing the source of the muscle pain side-effect associated with statin use. The work was very detailed at the molecular level and demonstrated clearly that the pain was associated with in infux of calcium ions into muscle cells. 

The second was a finding that  most of the very many side effects of statins as described on the crib-sheet supplied with the drugs were actually not attrubutable statins at all. The muscle pain side effect though was.

The above findings are interesting at the scientific, the linguistic and legal levels equally. The first finding regarding the influx of calcium ions is important because it is well known that mitochondria rapidly and unselectively absorb these ions, swell and may burst as the outer membrane gives way. 

Nearly fifty years ago my first paper showed that mitochondria became more fragile to swelling with age. Then we did not know so well that their rupture and release of weakly bound Cytochrome C ( this binds less tightly with age) triggers cell death ... we know it well now and it is the source of muscle wastage (sarcopenia) in old age. So, Columbia's research shows why a side effect of statins is muscle pain but it's findings infer that all mitochondria  will swell as a result of the drug. It's just that it is not always fatal to the cell! Do this to damaged, senescent mitochondria in aged cells and the cell will die as the mitochindria rupture.

The second finding's announcement was laughably 'straw-man' and linguistically manipulative.  The imaginary side effects listed on the drug sheet turn out to be, well, imaginary so can be crossed off,  and the confirmed side-effect (see above) is very rare so please ignore

... so the authors conlclude that the drugs are actually 'safer' than we thought and their role in tackling 'bad-cholesterol' is an even better option for now reassured people. 

Outrageous, my dim GP will no doubt be persuaded by this Pharma's ChatGtp bot generated blurb but this week's message is actualy the opposite. It's that statins cause severe change in calcium flux in muscle cell and this side effect is confirmed as real, ...  and the reasearch provides a clear causal path to sarcopenia in the vulnerable populations prescribed the wonder drug.

To get the message above though you will need at least a PhD in mitochondrial biochemistry and a working ability detecting thematic meme reasoning. 

Or in the opposite scenario, to be reassured, you will need a) a trust in big Pharma struggling to sell its wares, b) faith in your GP's scientific knowledge and c) an admiration for the Mandelson level of manipulation reached by generative AI

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.