Final Complexity is Less Relevant than that of Root Causes

I think we can all agree that, separately, each of aging, cancer, and Alzheimer's disease is a complicated phenomenon. Is cancer more or less complicated than aging, however? Are the likely several different disease processes leading to a similar end presently lumped under the heading of Alzheimer's disease more or less complex than either cancer or aging? I think that arguments could be made for any ordering of the three, though not all of them are good arguments, and anything that fits in this short blog post is going to involve a fair amount of hand-waving. We could compare the funding and researcher man-years devoted to understanding each, for example, or papers published, or some other similar research metric. I suspect that cancer wins by those measures, if we airily assume that greater amounts of funding are led by the fact that there is much more to catalog at the level of genes, proteins, and cellular mechanisms. I don't think that this is a safe assumption.

If we look at the SENS vision of aging, or indeed any damage-based model of how and why we age, we might say that aging is more simple than Alzheimer's, or more simple than any age-related condition. Aging stems from simple root causes, which expand out into massively complex and varied failure modes as damage interacts with damage and systems flail and fail in any number of ways. To draw an analogy, the rust that eats iron structures is a very simple, homogenous thing - a trivial set of a few chemical reactions, easily described, easily prevented. Yet a structure can fail in countless ways due to rust, as the progression and damage caused is stochastic. Which girder or support will be eaten to breaking point first? Similar structures might fail in similar ways more often, perhaps because they allow moisture to linger in the same places.

But you get the point: from simple causes great complexity can arise. The more complex the structure, the greater the number of failure modes that simple forms of damage can cause. We humans are tremendous complex, vast, interlinked arrays of molecular machinery, and in most modern theories of aging the few rusts we are theorized to suffer (some with much more evidence than others) are pretty simple at root. Thus any age-related condition must be more complex than its cause, aging, by virtue of being an end result rather than the cause of that end result. That is one way of looking at it. Another is to view the end state of aging as a whole and measure that complexity - which is obviously also much more complex than the simple processes that gave rise to it.

Does the complexity of the end state of aging matter, however? Or for that matter, the end state of cancer or Alzheimer's disease? This is not an idle question, as it points to the consequences that result from different core philosophies or approaches in medicine and medical research. Do we fix a problem by working to understand its end states and then try to clean up after or block every branching failure mode, or do we aim to remove the root causes and then let our biology try to restore itself?

That is not a question with a correct answer for all times and places: sometimes it isn't enough just to remove a root cause, sometimes the root cause is unknown. It is clear, however, that when it comes to age-related conditions a great deal of modern medicine runs along the lines of being an ever more sophisticated means of sticking a finger into the rapidly eroding hole in the dam, rather than repairing the hole in a way that will last. Consider the widespread efforts to safely remove amyloid beta in Alzheimer's disease, for example: it seems likely that this is not a case of treating root causes, which remain poorly understood at this time, but rather cleaning up the most evident of the biological signatures.

The regulatory structure for medicine and medical research in the US and Europe biases researchers towards the goal of producing what are ultimately less effective treatments for end causes. The system is so set up that the path of least resistance is to research some part of the complex pathology of a late-stage disease, where there is more room to carve out something that can be patented, and then build what are essentially palliative medicines for people who are very sick, having long suffered their particular named condition. Prevention and root causes don't yet get anywhere near as much attention. When it comes to aging itself, it isn't even legal in the US to try to produce and commercialize a clinical therapy that might do some good.

But prevention and root causes are exactly where the attention should be when it comes to aging and age-related diseases. Root causes are simple, end stages are complex: that is reflected in the cost and time required to produce therapies. The way to harness the complexity of our self-repairing biology rather than fight against it is to look to removing causes rather than cleaning up after the spreading tree of secondary and tertiary consequences. This has long been understood by the public and researchers alike when it comes vaccination, poisons, and all sorts of other areas of medicine. Somehow it has gone a little astray in the matter of aging and age-related disease. That must change.


Considering all the problems of longevity research in the US, what are the biggest efforts (by the SENS Foundation or others) in other countries?

Posted by: John at February 10th, 2013 12:36 AM
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