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.