System Complexity Theory of Aging, Nutritional Metals

System Complexity Theory of Aging in a Nutshell

Some molecules are essential for biological assembly. The requirement for these essential molecules exists for both the entire organism as a whole, as well as for each part of the organism independently. These required molecules includes metals, essential amino acids, and vitamins. Among these required substances, the metals are unique in carrying an ionic charge (copper, zinc, and magnesium all can carry a 1+ or 2+ charge in solution).

When the body is at equilibrium, these charges are neutralized by association with a protein. When that equilibrium is disturbed- for example, during an inflammatory reaction- oxidizing substances are released, and in response the metals become unbound, neutralizing electrons and bringing the inflammatory reaction to an end.

These ions are potentially toxic in unbound form, yet lethal in their absence. A lot of structure and function has evolved around them.

These metals and their neutralizing proteins present both a problem and an opportunity for the evolution of a self-assembling system. Each carrier protein must be large to function effectively to isolate the ionic charge; and yet the metal and protein together must be complex enough to entail behaviors that release or retain the charged ion for the particular needs of each separate part of the body.

Biological system development must be coordinated to ensure neither too much nor too little of nutritional metals occurs at any location. Whenever they are in short supply, a generalized adaptation syndrome (see Selye hormonal regulation of stress) occurs, including the release of the catabolic stress hormone cortisol. Cortisol is globally distributed with the vascular supply and functions as a general call to dissolve tissue.

But the body is composed of parts. These parts are arranged in parallel on the vascular supply.. This parallel architecture results in competition among the separate body systems to catabolize and release stores of these nutrients when stressed.

The system complexity theory of aging states that the catabolic competition among systems in vascular parallel determines which diseases of aging predominate for an individual.

A typical example of aging due to a failure of complexity would be a mild chronic tissue copper deficiency, leading to a reduction in the function of lysyl oxidase (a copper dependent enzyme that stabilizes collagen and elastin), then a decline in production of the enzyme as the body adapts to a lower presence of the lysyl oxidase enzyme (“use it or lose it”), followed by a further reduction in production of collagen and elastin, leading to multiple manifestations of aging: skin wrinkles, stiffness of the aorta and thus high blood pressure and thus perhaps heart attack or failure, and reduced flexibility and skeletal problems and back pain.

Here, the cause of health failure is traced back through copper deficiency, to a reduction of the copper-dependent lysyl oxidase enzyme, to a reduction of the production of collagen and elastin in aorta and skin and back, and finally to clinical disease.

A second component of the System Complexity Theory is the following identification of biological failure with limits to complex assemblies:

Biological structural self assembly is strongly constrained by the chemistry of these nutritional metals. Having reached the limits of this design constraint, the onset of the health failures of aging are the manifestations of this assembly constraint in reverse.

That is the complexity theory of aging in a nutshell.

As we age, there are changes in the conformation of proteins (proteins age) and that is associated with reduced ability to carry and properly release their metals. The reduced function leads to reduced feedback of the functional level of the metal, and so less stimulus for replacement and repair. There is less need to manufacture metabolically expensive proteins to support functioning with a reduced amount of metals, forming a negative feedback loop which is called aging.

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In terms of nutritional intake, it is not so important how much you take in. What matters most is what you can hang on to.

Levels of metalloproteins and enzymes are best measured by nail and hair analysis, which provides information on how these molecules are being used by tissues. In contrast, the serum changes only after we have slid considerably down the hill in our ability to maintain complex tissue assemblies. For example, a strong value for copper in nails, rather than serum copper or the serum copper binding protein ceruloplasmin, is a better way to assess whether you are adequately absorbing copper for total body needs. There is no generally useful serum marker for monitoring total body copper, zinc, and magnesium tissue absorption, or to monitor therapy during supplementation.

The best assessment of tissue uptake of nutritional metals is by hair or nail analysis, which will indicate how much the body has actually absorbed and put to use in tissue for the previous weeks to months, the time during which the nail or hair was growing and assembling tissue.

These three metals are carried on albumin at the same binding site, and interfere with each other during oral intake and supplementation. Effective oral supplementation of metals is increasingly limited with aging due to reduced binding of old proteins and also hormonal changes of aging stress. The best way to supplement these factors would transdermal, as they are absorbed over 12-48 hours, allowing time for the body to respond to the increased availability of nutrients by increasing the production of holding factors (metalloproteins, albumin, and enzymes).

I'm doing some studies in this area and will report if I find anything useful. While working with transdermal copper I have stopped using GlyNAC and so far feel fine. (Note that copper supplementation by itself markedly increases glutathione, which was the original impetus to using GlyNAC).

In the meantime, enjoy browsing through any references below that sound interesting to you.

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Note on use of the term “complexity”

Biological systems undergo a continuous process of destruction and repair. The two processes are not symmetric; it is in a sense more “complex” to build a house than to tear it down. For those interested in a more rigorous definition of complexity, I use the term as defined by Julian Barbour et. al. in the Complexity paragraph in a gravitational arrow of time to characterize the growth of complexity in physical systems.

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