Why You Can't Just Flip Switches

Biology is complicated. We are built out of a million evolutionary optimizations, and evolution loves the reuse of component parts. Every newly evolved mechanism will quickly find its place in other evolved systems, while still being used in its original capacities. The human cell is a big cat's cradle of macromolecules, each with twenty-something different purposes, operating in interacting feedback loops and dynamically regulated processes.

When your research indicates that molecule A is the problem in medical condition B, you can be fairly sure that bluntly manipulating molecule A in order to treat B will completely mess up vital systems X, Y and Z.

A good example of this principle came to my attention today, in the form of PGC-1alpha, a protein that's right in the middle of all sorts of important processes. I put out a post a few days back, in fact, on research demonstrating the role of PGC-1alpha in calorie restriction and mitochondrial function.

So, you might think, another target to better recreate the beneficial effects of calorie restriction on health and longevity - without the dieting. Not so fast, now:

Researchers at Dana-Farber Cancer Institute have found a previously unknown molecular pathway in mice that spurs the growth of new blood vessels when body parts are jeopardized by poor circulation.


Bruce Spiegelman, PhD, and his colleagues at Dana-Farber discovered that PGC-1alpha - a key metabolic regulatory molecule - senses a dangerously low level of oxygen and nutrients when circulation is cut off and then triggers the formation of new blood vessels to re-supply the oxygen-starved area - a process known as angiogenesis.

Blood vessel formation is not something to be tinkered with lightly - and that's just one of the many processes that PGC-1alpha is involved in.

This hyperconnectivity and reuse of processes, proteins and genes, this rampant complexity, is why aging researchers who focus on metabolic and genetic engineering - which is to say the bulk of the field - see healthy life extension as hard, and any meaningful progress in terms of additional decades as remote in the future. They believe the only viable way forward is to re-engineer our biology into something tougher and better, to slow the processes that cause damage and aging. I agree that this goal is a great challenge, and will likely still be a great and ongoing challenge when the era of hypercomputing and molecular manufacturing is upon us some decades from now.

Fortunately, a much better approach to complex systems exists: work with the examples you have. We have working examples of our biology in good health and operation. Similarly, we have examples that are age-damaged and failing. Rather than try to build some completely new complex biology to resist the ways in which age damages us, we should focus on identifying and reversing the specific differences between youthful metabolisms and age-damaged metabolisms.

Given the level of knowledge today, significant progress in reversing aging - repairing damage, reversing changes in metabolism - is much more plausible for the decades ahead than producing a new slow-aging human metabolism. In addition, any successful therapy that repairs some facet of the damage of aging in our metabolisms can be used over and over again by the same individual. Keep the damage beneath the level at which it causes the degeneration of aging, and you can continue to be healthy and youthful for so long as you please. This is obviously far more beneficial and valuable than a therapy that merely slows aging - slowing aging is of no use to the aged.

The greatest challenge in the scientific infrastructure and community of aging researchers today is to change the focus from slowing aging (slow, inefficient, producing less useful medical therapies) to repairing aging (more efficient, more rapid, producing more useful medical therapies). It is this challenge that spurs groups like the Methuselah Foundation and affiliated researchers. This may seem like an esoteric battle to some, but the future of life and health for everyone alive today depends upon it - which means that we should all pitch in and help.


Good post, identifies the difference in perception. I would definately love to work on that kind of hypercomputing challenge so that you wouldn't need therapies any more (or more realistically: as frequently) but living to see the day that is possible is more important so I'd rather take the easy route there.

Difficulty and realism aside, let's look at it from the perception of public acceptance: people have all these biases against genetic engineering and stuff, especially today, so they are very biased against accepting or funding such research. Repair-based rejuvenation approaches would be less controversial in this regard, I think.

Of course, some repair-based initiatives (like mitoSENS) do involve some manipulation of the DNA, though even there it's less controversial since you're moving stuff around, not altering existing DNA.

Posted by: Tyciol at March 14th, 2008 4:02 PM
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