Ferociously Complex, Is Metabolism

Metabolic processes are no more than the changing operation of our biochemistry, day to day, and across our lives. It is a hugely complex and dynamic metasystem built of many interacting complex systems. Decades of work remain, even taking into account accelerating progress in biotechnology, to understand metabolism to the point of being able to radically change it. This, as I am given to point out, is why many aging researchers are pessimistic about progress: they believe that the only way to extend healthy life is to re-engineer our metabolism. They think, rightly, that this is a huge undertaking as seen from our present vantage point.

In that vein, I thought I'd point out an open access paper on bee metabolism today. It's not so jargon-heavy that it's impossible for the layman to read, but it gives a very good impression of the sheer complexity of biochemistry - even in a small, comparatively simple insect - and the breadth of what is left to discover. The ocean of metabolism is deep, and we're still fishing around the edges; the research community may have a big list of what's in there, but that's not the same as understanding all the important details of its operation. A moving engine is more than the sum of its parts and materials.

Bees are an attractive point of study because different individuals within the species - queens, workers, drones - have widely divergent rates of aging. This is a strategy for making inroads into the unknown: find a selection of items that are similar yet exhibit different very behavior, find the small differences that exist between the items, and then seek to understand how those small differences lead to such disparate results. In bees, the antioxidant chemical vitellogenin appears to be a good candidate:

Whether this is the actual mechanism by which queens achieve both fertility and long life remains to be seen, Robinson said. In any event, this study suggests that vitellogenin plays a vital role in queen bee longevity, he said, particularly since the honey bee lacks many antioxidants commonly found in other species.

But take a look at the paper mentioned above: vitellogenin is just one item in a long, long laundry list.

Back to engineering longevity: the Strategies for Engineered Negligible Senescence, or indeed any repair-based approach to aging, employs a similar comparison strategy to sidestep our comparative ignorance of metabolism. Take a young metabolism and an old metabolism, and list all the differences between the two. Establish which differences are secondary to others, and in doing so winnow down the list into a set of primary root causes for all the change and degeneration that happens to our biochemistry across the years. Those root causes become the targets for repair strategies.

I should note that all this work has been accomplished already, over the past half century. The list of root causes for aging already existed, complete as of the 1980s - not that anyone then knew that no more would be found in the following two decades. These root causes are all forms of accumulated damage caused by the normal operation of our metabolism: specific forms of wear and tear that lead to a wide variety of age-related conditions and ultimately death.

It doesn't matter that we fall far short of a full understanding of how all these primary and secondary changes fall into place - how exactly damage A leads to damage B that leads to degeneration - the process of comparison and elimination between old metabolisms and young metabolisms shows us the narrow window through which we can focus our efforts to move forward. All additional understanding beyond this window can only help, but it isn't strictly necessary.

This paradigm is how we can move beyond the awe-inspiring complexity of metabolism, and move beyond the limitations of the vast project necessary to understand and manipulate our metabolisms. By focusing very narrowly on the identified changes that occur in our biochemistry with age, and setting forth to repair those changes, we have the chance to make significant progress towards engineered longevity in our lifetimes.

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