Greater Understanding, Metabolic Tinkering
Permalink | View Comments (2) | Post Comment | | Posted by Reason

I'm not exactly an advocate of metabolic tinkering as anything more than a stop-gap measure for healthy life extension research - in absence of anything better in the immediate pipeline. It's quite unclear as to the sort of extension of life span you could engineer in humans or other primates simply by tweaking metabolic controls, even though a 50% increase in life span with minimal side effects seems like a very reasonable near future goal for mouse studies these days. Arguments over the effectiveness of calorie restriction on life span in humans could equally be extended to other methods of metabolic control, for example. If we could even manage a decade or two in humans via these methodologies, with a nice reliable technology platform to back it up, that would be great - but I don't think we should be devoting all our resources to metabolic manipulation. It just doesn't have much of a future beyond this optimization, and we want to see much larger gains in healthy life span. To achieve those gains, we have to move beyond optimizing metabolism into repairing or preventing age-related cellular damage or more advanced technologies.

With that all said, however, it's nice to see that research groups armed with modern biotechnology are up to delivering a continual stream of information regarding the mechanisms of metabolism and longevity. From the latest interesting research:

The longevity-promoting effect of reducing CLK-1 activity that was initially observed in C. elegans is conserved in three different genetic backgrounds of mice. In 129Sv/JxBalb/c mice for instance, reducing activity of the gene mclk1 (mouse clk-1) results in a prolongation of lifespan of about 32%. The inactivation of mclk1 gene, which encodes a mitochondrial enzyme, decreases reactive oxygen species (ROS) levels, the toxic molecules that damage proteins, lipids and DNA, and this likely explains this increase in lifespan.

Commenting on his study, Professor Siegfried Hekimi said: "Increased lifespan can be considered a marker for a physiological condition in which oxidative stress is reduced. Extrapolated to the pathophysiology of human diseases partially decreasing CLK-1 activity by pharmacological means should limit oxidative stress and consequently, prevent or slow the development of common age-related degenerative diseases such as Alzheimer's disease, Parkinson's disease or atherosclerosis. Such new therapies may also be beneficial to treat more acute diseases where oxidative stress is also significantly increased such as ischemia-reperfusion injury."

It's both amusing and saddening to watch commentaries such as the one above completely avoid any mention of human healthy life extension even in circumstances where you would think it was unavoidable. This is the atmosphere in which modern gerontology takes place; age-related disease is bad, but no-one must ever say anything about extending life spans.

A life extension of 32% is a good figure for mice - it's in the same ballpark as other life-extending genetic tweaks thought to work by reducing free radical populations. Or calorie restriction for that matter. As always, I eagerly await studies of the healthy life span of mice that possess all of the presently known life-extending genetic modifications.

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Comments

I think there is only so much you can do by messing with metabolism. Ultimatly you will still age but maybe a little bit slower. Thats why efforts are best directed to something like SENS. To get in there are clean up the mess before it leads to pathology. I really believe that aubrey has this right and I hope even more people starts listening to him in the near future.

Posted by: Matt at October 26, 2005 10:08 PM

My first question would be: So what pharmacological means is currently available to decrease CLK-1 activity? I'll take a 32% life-span increase as a temporary stopgap while I'm waiting on a more long-term solution.....

Posted by: Glenn at October 28, 2005 11:46 AM
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