July 04, 2007
Telomerase Elimination For Rejuvenation Problematic

In order to limit the number of times that cancer cells can divide biogerontologist Aubrey de Grey has proposed elimination of the gene for telomerase in stem cells introduced into aged bodies. He calls this Whole-body Interdiction of Lengthening of Telomeres (WILT). Well, with a new report about telomerase enzyme published in the Proceedings of the National Academies of Sciences USA that proposal seems problematic. According to this new result telomerase does not just lengthen the caps on the ends of chromosomes.

Telomerase is a cellular reverse transcriptase that extends one strand (the G-strand) of the telomere terminal repeats. Aside from this role in telomere length maintenance, telomerase has been proposed to serve a protective function at chromosome ends, although this is not well understood mechanistically. Earlier analysis suggests that, in the pathogenic yeast Candida albicans, the catalytic reverse transcriptase subunit of telomerase (TERT/EST2) can protect telomeres against nucleolytic degradation. In this report we demonstrate that the RNA component (TER1) has a similar function; in addition to complete loss of telomerase activity and progressive telomere attrition, the ter1-ΔΔ strains manifested a dramatic increase in the amount of G-strand overhangs, consistent with aberrant degradation of the complementary C-strand. We also demonstrate that a catalytically incompetent EST2 protein can suppress such overhang accumulation in the est2ΔΔ mutant to the same extent as the wild-type protein. Altogether, our data support the notion that the Candida telomerase core components mediate a protective function through a mechanism that is independent of its catalytic activity.

If telomerase is keeping chromosomes stable then taking away telomerase could cause more things to go wrong sooner. I've never been enthusiastic about WILT because we need a cure for cancer for all our cells that do not already have telomerase knocked out in them. We have lots of cells all over our bodies that are getting older and at greater risk of becoming cancerous. Short of replacing our entire bodies WILT will not eliminate the risk of death from cancer.

Fortunately, I expect cancers will become very curable. We'll develop immuno-therapies, gene therapies, cell therapies, and even nanobots that will seek out and selectively kill cancer cells. Falling costs and greater sensitivity of genetic tests and cellular tests will allow us to understand in great detail all the myriad ways in which cancer cells differ from normal cells. We will develop much more powerful tools for targeting cells based on these differences. Cancer is curable.

Share |      Randall Parker, 2007 July 04 05:43 PM  Rejuvenation Cancer

Jonathan said at July 5, 2007 1:43 PM:

I fully agree with you. I am a fan of the SENS project, but have never been a fan of WILT. It always seemed like to extreme of a measure just to stop cancer. De Grey has always been pretty realistic about the SENS approaches he suggests though. He always says that some of the approaches will most definitely not work and other approaches will need to be used.

Kurt9 said at July 5, 2007 4:24 PM:

The test of De grey over the coming years will be how open he is to updating the SENS strategy as new knowledge comes in and is applied. I think his conferences will be good for this. The third SENS conference looks like it will be significantly better than the previous two.

I agree that I think WILT is an extreme measure that will likely prove unneccessary as the knowledge of the molecular-biology of cancer and stem-cells is worked out.

Hopefully Anonymous said at July 6, 2007 2:01 PM:

Kurt9, I think what De Grey needs is lots of quality competition. Search improvement is fueled by Google vs. Yahoo vs. Microsoft competition. Smartphone improvement is fueled by Blackberry vs. RAZR vs. Sidekick vs. now iPhone. Who are De Gray's competitors as theorists on how to solve human aging. We need several solid competitors, not one guru.

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