The Era of Unifying Theories

Scientific progress goes through cyclic periods of fragmentation followed by synthesis. During fragmentation, many different groups toil away at their own little pieces of the great unknown. Each group generates data that, at first, appears to have little to do with other efforts. As the data piles higher, correlations start to appear - and so do the efforts at synthesis. Gradually, the focus in a field shifts from finding new information to making sense of what is known, pulling it all together such that links, correlations, and chained mechanisms are understood. Then they next great unknown beckons and the process of fragmentation starts once more.

At present the grand study of human biochemistry is moving from fragmentation to synthesis. It is still the case that some different specialties know little of one another's work. Researchers look at the same mechanisms and compounds, giving them different names and assuming different dominant roles in biochemical processes, all the while missing out on the enlightenment that a complete picture can bring. But that state of affairs is generally on the way out, helped by modern information technology. The cost of knowledge is dropping precipitously, and so the process of synthesis becomes easier and starts earlier:

In past years, I was fond of comparing biogerontology to the tale of the blind men and the elephant: everyone was approaching the problem from different directions, unable to see the big picture - and reaching conclusions that had more to do with the direction of approach (i.e., initial biases) than the fundamental importance of any given observation.

But this analogy is becoming increasingly less apt, and we may be on the verge of the era of unifying theories in the biology of aging.

What causes aging? The various subfields of biogerontology answer this question in very different ways. To vastly oversimplify: In one corner we have metabolism, including the related stories of sirtuins and calorie restriction; in another corner, we have DNA damage and stochasticity of gene expression. (Already we're seeing the unifying tendency of recent findings: a few years ago I might have put those four items in four separate corners, but on the basis of recent reports I feel comfortable starting to bin them together. There are those, however, who would argue I'm being premature if not outright inaccurate in so doing.) In both corners, one could make a legitimate claim that the phenomenon in question has serious explanatory power regarding a fundamental mechanism of aging or longevity assurance - but is there a connection between the two?

This is a view within the mainstream focus on metabolism, DNA damage and the like - quite different from the Strategies for Engineered Negligible Senescence approach to aging science - but you should read the rest; it's very interesting.


Wasn't it just a few weeks ago that Sinclair proposed the unifying theory ? That is, that SIR1 has been shown to serve a dual role. It's primary role is to protect the chromatin which wraps the DNA and keeps genes silenced (hence the word "silence" in SIR). A secondary role is to repair DNA breaks. As a person grows older, and there is free radical DNA damage, the SIR1 protein leaves it's guard on the chromatin to increasingly repair increasing DNA damage. In so doing, the chromatin comes unwound and genes begin to express proteins when they would be otherwise silent. Hence, increased SIRT1 during CR allows DNA repair and keeps the genes silent which should be, i.e. youthful gene expression.

Seems to me, it would be a nice thing to provide more SIRT1 and help with DNA repair independently to attack the same problem from two ends.
- Joel

Posted by: Joel at December 11th, 2008 1:17 PM
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