A Tale of Telomerase

Michael Rae has written a long post at the SENS Foundation on the topic of the recently published Spanish study that produced life extension in mice through a telomerase gene therapy. He has been following this line of research closely for some years, and has been critical of the results reported in the past. The post is well worth reading for a better view of both the chronology and the limitations of the work that led to this latest result.

Tale of Telomerase: Lessons and Limits in a Late-Life Launch

The connection between telomeres, telomerase, and cellular and organismal "aging" was a matter of significant scientific interest but little public awareness until the early 1990s, when Dr. Michael West founded Geron Corporation. In the process of launching that venture, and in the following years, West succeeded in embedding a controversial thesis deeply into the public imagination: that the (re)activation of telomerase in somatic cells could retard or even reverse the degenerative aging process. There were always problems with this thesis, and with public (mis)understandings of it, but its sheer simplicity and public prominence has in direct and indirect ways advanced scientific research that has answered many of the questions that thesis forced upon the scientific community, and opened up important new avenues for research in telomre biology and in biomedical gerontology.

The most direct and important fruits of that expansion of research into telomerase have been studies on the pharmacological and transgenic activation of telomerase in the tissues of aging mice. Several such reports have appeared over the years, each hailed prematurely as evidence of the life- and health-extending power of the enzyme. The most important of these studies have been a series of experiments by MarĂ­a Blasco, PhD, SENS Foundation Research Advisory Board member and Director of the Molecular Oncology Programme at Spain's National Cancer Research Centre (CNIO). A tantalizing new report in this series has just appeared -- but to understand it in context, we will first review those that led up to it.

You should read the whole thing; it is very educational, and a good illustration of the way in which there are no sudden breakthroughs in science - just sudden attention paid to steadily ongoing progress. Each new advance rests upon decades of past work and the efforts of a range of other research groups. It also illustrates the need to look past the headlines to pick at the details of heralded research. For example:

several caveats must be noted about the results themselves, and their implications for medical therapies against the degenerative aging process in humans. As in the previous studies, the apparent increases in survival in this new report were, in fact, ambiguous. The study was substantially underpowered to detect a true increase in maximal lifespan; and even taking the results at face value, the reported survival data - even for treated animals - were, once again, well within the range typical for well-husbanded, untreated control mice reported in other studies.

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Additionally, there was relatively little effort invested in ruling out a possible effect of Calorie restriction (CR) in this study.

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Presuming, however, that the life- and healthspan benefits reported in this study should be taken at face value, the ultimate question is their human translatability - and there are reasons to be skeptical that a similar therapy could be safely used to retard the degenerative aging process in humans. Some would note first that safe and effective gene therapy is not yet available for our species - but that, like many other matters in biomedical gerontology, is only a matter of time and investment. Of greater concern is the safety of telomerase therapy, granted the very different body plans of humans as compared to mice.

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