Whole-body Interdiction of Lengthening of Telomeres (WILT) is the Strategies for Engineered Negligible Senescence (SENS) answer to cancer, filed under the OncoSENS project category. Get to the root of it all, and yank that root out:

This is a very ambitious but potentially far more comprehensive and long-term approach to combating cancer than anything currently available or in development. It is based on the one inescapable vulnerability that all cancer cells share in common: their absolute need to renew their telomeres, the long stretches of gibberish DNA that cap their chromosomes.

Telomeres fulfil a role that is similar to that of the nibs on the tips of your shoelaces, keeping the DNA from becoming frayed and unravelled. Each time a cell reproduces, the telomeres become a little worn down, and when a cell runs out of telomeres it quickly self-destructs.

Because cancer cells reproduce at a furious pace, they quickly reach the ends of their telomeric "ropes," and need to find a way to exploit the cell’s natural machinery for renewing telomeres (telomerase and [alternative lengthening of telomeres, or ALT]) to restore normal telomere length, or their growth will come to an end. The thorough elimination of these genes from all of our dividing cells thus spells the doom of cancer.

So eliminate telomerase, and eliminate whatever turns out to be the gene or genes necessary for ALT. Cancers are little evolution engines, capable of mutating their way around pretty much any chemotherapy given enough leeway - but they are vanishingly unlikely to be able to mutate their way into an entirely new gene to lengthen telomeres. That's too big a handful of disabled fundamental machinery to work around.

As it happens, WILT has never been my favorite strategy in SENS - which is interesting, given that it is just as scientifically sound as the rest. I think that my instinctive objection stems from it being the one portion of SENS we can point to today and say "that would need a touch-up procedure every 10 years ... or else." The need to return to the clinic exists because a WILT recipient has no more telomerase anywhere, including - especially - the stem cell populations vital to health. There are genetic diseases that tell us what happens when your stem cells stop being able to lengthen their telomeres; it's a slow and unpleasant way to go, taking about a decade to show up in earnest, and running downhill from there as regeneration and repair starts to shut down.

So the WILT recipient of 2030 would have to receive new stem cell populations, or more likely some form of gene therapy that restored telomere length in the existing populations, every decade or so. To me, ten years is not a broad enough margin to account for error, falling into bankruptcy, heading out to the backwaters of the solar system and back again, and so forth. It's all too easy for something to go wrong. The ideal hypothetical longevity therapy (or component of longevity therapy) lengthens your life span even if you never see another clinic again - but WILT dramatically reduces your life span under that set of circumstances.

A procedure every ten years compares very favorably with developing cancer, of course. But do we need a final solution like WILT to make it through decades of later life? Will the continuing advance of more conventional "detect, target and pinpoint cell destruction" cancer medicine get the job done for long enough to make it into the next phase of medical science, sometime in the 2040s?

The risk of cancer in any tissue increases with age - and as for most failing machines, quite dramatically so in later life. This stems from underlying changes in biochemistry and the simple rules that determine failure rates in machinery based on gradual wear in component parts - possibly the shortening of your telomeres, possibly damage to stem cells, possibly something else, possibly all of the above. Is it good enough to have a good after-the-fact cure on hand when the risk of occurance is increasing enormously with each passing year? Is there a point past which a good therapy is just overloaded by sheer weight of new cancer bursting from your cells, and where does that point occur?

Ultimately, we would want to change our biochemistry so as to prevent cancer from occuring at all. Like all projects aiming to safely re-engineer a very complex system, this will be challenging indeed - but it will get easier with time. At what point will we need to have absolute cancer prevention in hand to beat the curve of aging, and thus remain alive and in good health to take advantage of the next anti-aging technology in line? At what point does a cure for cancer fail us?

It might also be the case that eliminating telomerase reveals that telomerase has other important roles in the cell. The Methuselah Foundation is in fact funding a study on this very issue. Just a few days ago, I pointed out research suggesting that telomerase actually slows the rate of damage suffered by mitochondrial DNA, and therefore influences life span by dampening the biochemical processes that amplify and spread that mitochondrial damage throughout the body. If verified, this means that eliminating telomerase will speed up aging through these mitochondrial damage mechanisms.

That suggests that WILT can only be safely implemented on top of a successful project to either periodically replace your damaged mitochondrial DNA, or render mitochondrial DNA damage moot by moving the vital portions of it into the cell nucleus. The latter, of course, is a part of SENS.

Posted by Reason at June 10, 2008 4:15 PM | TrackBack (0)