Thesis 20

Thesis #20 – A single pharmaceutical or nutritional substance will never cure aging, for aging is not a simple physiological disease or dysfunction, but the de-tuning of adaptation with adult age.

The quest for a substance that might arrest aging, or even reverse it, has been perennial.  We have myths and records of this quest from both Eastern and Western Eurasian civilizations.  Fountains of youth, philosopher’s stones, magic fruit or herbs that sustain youth, fortunate climes in which healthy centenarians live, they are all to be found in the written records of the great civilizations.

And these hopes and fables are still with us.  The biotech company Geron was founded on the reductionist premise that determining how to give our somatic cells the capacity to remain “young” and proliferative would “cure the disease of aging.”  Their focus was on the telomeres that are the caps to our chromosomes.  As human cells divide under glass in laboratories where they can be kept alive outside of our bodies, their telomeres progressively shorten.  When this shortening has largely eroded the telomeric caps, cell division slows and comes to a stop. Using this idea to “cure aging” is a bit more complex than a fountain of youth or the philosopher’s stone, but similar in its mythic aspirations.

Amazingly, in the 1990s, it proved possible to engineer human cells that produced enough telomerase to refurbish telomeres.  The result, as the founders of Geron had hoped, was that these cells could proliferate indefinitely in human cells cultured under glass, with none of the slowing proliferation that was interpreted as “cell aging” for the last third of the 20th Century.

Geron’s attention then turned to identifying substances that might keep telomerase activated in the somatic cells of our bodies.  And such substances have been found.  For example, a component of the Chinese herb astragalus called “TA-65” is known to foster telomerase activity.  TA-65 is now being marketed as a telomerase activator by a company called TA Sciences for use as a nutritional supplement to stave off aging, rather than a drug for a specific medical condition.  There have been some promising clinical results from a double-blind placebo-controlled study of the effects of TA-65.  Oprah Winfrey has been quoted as saying, “I want longer telomeres.”  So is this the long-sought fountain of youth?

Telomerase activation exemplifies many of the difficulties with “solving the problem of aging” using the tools of molecular and cell biology.  Malignant tumors have higher levels of telomerase activation, in most cases, than our normal somatic cells.  This makes sense, in that cancer cells have relatively unbridled proliferation.  Thus the problem for telomerase activation is that it is not necessarily good to have cells in our bodies with uncontrolled proliferation.  Rather, the human body has multiple mechanisms, including telomere shortening, which actively forestall such cell proliferation.

More cell proliferation in our bodies is a double-edged sword.  It would provide more cells with which to repair tissue damage, but it might put more of our cells on the road to becoming malignant.  Finely tuned to target just those cells which would be most beneficial to keep proliferating, telomerase activation might be a useful therapy.  But it is unlikely to alleviate all the things that go wrong in our bodies.  And turning on cell proliferation generally might actually shorten life, by fostering cancer.

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