More on CLK-1 and the Retrograde Response
You might recall that the gene CLK-1 can influence longevity in a range of species:
CLK-1 - or clock-1 - is a gene that affects lifespan, most likely through its influence on mitochondrial activity. It's the standard story, or at least appears to be: anything that can lower the rate at which mitochondria damage themselves will extend life in flies, mice, and so forth.
Here's more on CLK-1 in yeast and worms; an open access PLoS Genetics paper:
Mitochondrial respiration generates energy in the form of adenosine triphospate (ATP), a molecule that powers many cellular processes. When respiration is inhibited in C. elegans, rates of behavior and growth are slowed and, interestingly, lifespan is extended....
We find that inhibiting respiration increases the expression of genes predicted to protect and metabolically remodel the animal. This pattern of gene expression is reminiscent of the expression profile of long-lived respiration-defective yeast, suggesting ancient evolutionary conservation. Mutations in clk-1, which inhibit the synthesis of the respiratory-chain factor ubiquinone, produce gene expression, longevity, and behavioral phenotypes similar to those produced by inhibiting components of the respiratory chain.
We find that knocking down the activities of two similar genes - fsrt-1 and fstr-2- accelerates the behaviors and aging rates of clk-1 mutants ... Thus, fstr-1/2, which encode potential signaling proteins, appear to be part of a mechanism that actively slows rates of growth, behavior, and aging in response to altered ubiquinone synthesis. Unexpectedly, fsrt-1/2 are not required for the longevity and behavioral phenotypes produced by inhibiting the gene isp-1, which encodes a different component of the respiratory chain. Our findings suggest that different types of mitochondrial perturbations activate distinct pathways that converge on similar downstream processes to slow behavioral rates and extend lifespan.
Our mitochondria appear to be the crux of a great many evolved mechanisms of longevity, which continues to point them out as a good place place to start when trying to prevent or reverse the damage of aging.
I was very interested to note that in Aubrey De Greys open letter re: SENS.ORG he noted that the mitochondrial strand of SENS seems relatively close to completion. This seems like a pretty big deal if true. Reason, are you able to elaborate on Aubrey's claim at all? How close are we talking, realistically? And what impact, if any, would such success have on a) availability of medical interventions pre full fledged SENS, and b) respectability and further funding of SENS Foundation, in your opinion?
The step after "the biochemistry basically works so far as we can tell" is mouse trials. So assume five years if you're starting with old mice to see how much of an effect mitoSENS therapies have.
In terms of funding, very helpful. Anything that can be demonstrated as progress with practical application is useful.
As to medical interventions for humans: the FDA won't allow any intervention targeted at aging, so whatever development happens under regulatory oversight will be for mitochondrial diseases and narrow applications of the technology only.
If you want to see actual application to aging on a timeframe of a decade after the mouse studies are showing promise, you'll most likely want to see responsible groups in Asia or other less overregulated areas practicing the medicine and gathering data at the same time - but based on what's been happening in the stem cell field there's usually much less gathering of data than is helpful.